PHARMACEUTICAL COMPOUNDING LABORATORY
LABORATORY MANUAL
FALL 2003
DEPARTMENT OF PHARMACY
SCHOOL OF MEDICINE
UNIVERSITY OF ZAMBIA
LUSAKA, ZAMBIA
PHARMACEUTICAL COMPOUNDING LABORATORY
LABORATORY EXERCISES
FALL 2003
PROGRAMME COORDINATOR: Lungwani T.M. Muungo, Ph.D.
INSTRUCTORS: Mrs M. Mooto
DEPARTMENT OF PHARMACY
SCHOOL OF MEDICINE
UNIVERSITY OF ZAMBIA
LUSAKA, ZAMBIA
2
FOREWORD
This manual has been prepared in anticipation of the students that will be enrolled in Pharmaceutical
Compounding Laboratory sessions. It will permit the students to preview each laboratory exercise prior to
performing the work in the laboratory in order to be properly prepared. Background information on the
exercises has been provided in Pharmaceutics and Clinical Pharmacy lecture sessions. It is not intended
that all of the materials necessary to completely understand or fully carry out a particular exercise are
included in this manual. Each laboratory period is preceded by a laboratory lecture. More often than not,
additional information is provided, minor changes in detail are made, and obscure points are clarified. This
laboratory manual has been prepared for the current academic year and every effort will be made to
introduce new materials and exercises on a yearly basis.
Pharmaceutical Compounding: Pharmacists Heritage (Excerpt from Loyd V. Allen Jr., Ph.D.: The
Art, Science, and Technology of Pharmaceutical Compounding, 1998)
Historically, compounding has been an integral part of pharmacy practice, as shown by the following
definitions and references to pharmacy: (a) Pharmacy is the art or practice of preparing and preserving
drugs, and of compounding and dispensing medicines according to the prescriptions of physicians. (b)
Pharmacy is the art, practice, or profession of preparing, preserving, compounding, and dispensing
medicinal drugs and a place where medicines are compounded or dispensed. (c) Pharmacy is the science,
art, and practice of preparing, preserving, compounding, and dispensing medicinal drugs and of giving
instructions for their use. Compounding is a professional prerogative that pharmacists have performed
since the beginning of the profession. The heritage of pharmacy, spanning some 5000 years, has centered
on providing pharmaceutical products for patients. Pharmacists are the only health professionals who
possess the knowledge and skills required to compound and prepare medications to meet the unique
needs of patients. The apothecary is listed in the Bible as one of the earliest trades or professions.
Prescription compounding is a rapidly growing component of pharmacy practice. This change can be
attributed to a number of factors, including individualized patient therapy, lack of commercially available
products, home health care, intravenous admixture programs, total parenteral nutrition programs, orphan
drugs, veterinary compounding, biotechnology-derived products, and problem solving for the physician and
patient to enhance compliance with a specific therapeutic regimen. Pharmacists are creative and have the
ability to formulate patient-specific preparations for providing pharmaceutical care. Newly evolving
therapeutic approaches suggest that compounding of pharmaceuticals and related products specifically for
individual patients will become more common in pharmacy practice in the years ahead. Further,
compounding pharmacists develop a unique relationship with the patients they serve. They work hand in
hand with physicians to solve problems not addressed by commercially available dosage forms.
An article by Angel d’Angelo, RPh, editor of the U.S. Pharmacist, explains that compounding is our
(Pharmacists) heritage. There is no other professional license that allows for the extemporaneous
compounding of therapeutic agents.
i
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Complete pharmaceutical care must involve the dosage form, which might necessitate compounding a
patient-specific form not available commercially, possibly the preparation of a product without a
preservative or a specific allergy-producing excipient that must be removed from the formulation for
neonates and small children. With pharmacokinetic services, the need for individualized dosage units will
be required more frequently to meet these patient-specific needs. Pharmacists who compound have the
desirable and needed skills.
Pharmacists have a responsibility to serve their patients and to compound an appropriately prescribed
product in the course of their professional practice. It is the right and responsibility of pharmacists to
compound medications to meet the specific needs of patients. Pharmacists are ultimately responsible for
the integrity of the finished product prepared by them or under their immediate supervision.
Pharmacists are the only health professionals formally trained in the art and science of compounding
medications. Consequently, they are expected to possess the knowledge and skills necessary to
compound extemporaneous preparations. In 1995, the percentage of compounded prescriptions
represented approximately 11% of all prescriptions dispensed, which is a five- to tenfold increase in the
percentage of such prescriptions dispensed in the 1970s and 1980s. It is evident that the need for
individualized drug therapy for patients has been realized and is resulting in patient-specific prescriptions
and the compounding of medications that are not commercially available.
*I hope the words of Dr. Loyd V. Allen Jr., as summarized above, will stimulate students enrolled in
this course to take compounding seriously.
Lungwani T.M. Muungo, PhD
WRITING MATTERS
Writing is an essential tool for thinking and communicating in virtually every profession. Therefore, in this
course I expect you to produce writing that is not only thoughtful and accurate, but also organized, clear,
and consistent with the rules of Professional Standards and Language. If your writing does not meet these
standards, you may lose credit points and affect your academic progression.
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TABLE OF CONTENTS
Foreword ............................................................................................................3
Laboratory Schedule.......................................................................................... 6
Laboratory Rules ............................................................................................... 13
Laboratory No. I Solid Dosage Forms - Bulk and Divided Powders ...................... 18
Laboratory No. II - Hard Gelatin Capsules .......................................................... 30
Laboratory No. III - Aqueous Solutions and Syrups ............................................. 49
Laboratory No. IV - Non-Aqueous Solutions ........................................................ 61
Laboratory No. V - Polyphasic Systems: Solids Dispersed in Liquids ................... 76
Laboratory No. VI - Polyphasic Systems: Emulsions ........................................... 91
Laboratory No. VII - Semisolid Dosage Forms: Ointment Bases .......................... 106
Laboratory No. VIII - Medicated Ointments ......................................................... 122
Laboratory No. IX - Suppositories ....................................................................... 140
Laboratory No. X - Sterile Products: Parenteral and Ophthalmic Products ........... 155
COURSE
PLAN
Course Number
83979-336-01
Course Title: Pharmaceutical
Compounding Laboratory
Page:
Date:
Aug 20, 2012
EXAMINATION/GRADING POLICY
The examination schedule shall be distributed to the class at the beginning of the semester. The
class (through the President) may request changing any or all of the scheduled examinations to
the coordinator because of conflict with other courses only within the first ten (10) working days
of the semester. The coordinator shall attempt to accommodate this request while taking into
account the need to include a reasonable amount of course material in each examination. After the
final revision, no change in the examination schedule shall be permitted except under unforeseen
circumstances authorized by the course coordinator.
All students shall have the responsibility for presenting themselves regularly and promptly to take
the scheduled examinations of the course. To ensure fairness in the conduct of the
examinations, no tardy student to an examination shall be allowed into the examination room
after any student has completed the examination and has left the room.
All students are required to take all the examinations indicated in the schedule.
A student who fails to appear and take the examination on its scheduled date and time, shall earn
the grade of ″zero″ unless his/her absence is considered ″excused″ as explained in item #5 below.
An absence from an examination shall be considered ″excused″, if it occurs because of any one
of the following circumstances:
Hospitalization of the student due to illness or accident.
Death in the student′s immediate family (e.g., spouse, parents, guardians, siblings
and/or children).
Summons of the student to appear for Jury Duty or before a court.
In these cases, the absentee student shall submit documents supporting the above
claims (Hospital Admission Form, Death Certificate or Government/Court Subpoena) to
the Course Coordinator. Upon satisfactory verification, the student shall be allowed to
take a make-up examination.
NO OTHER EXCUSES WILL BE ENTERTAINED FOR A MAKEUP EXAMINATION
REVIEW OF EXAMINATION PAPERS: Semester examination will only be reviewed for the purpose
of grade changes within five days after the announcement of the examination results.
CHEATING IN THE EXAMINATIONS: All examination shall be proctored by faculty and staff members to
prevent and discourage cheating. If cheating is suspected, all proctors will act as witnesses in accordance
with procedures set forth in the Howard University Academic Code of Conduct. Students should read the
″Academic Code of Conduct″ that is published in the H-Book and the Student Reference Manual and
Directory of Classes. The ″Academic Code of Conduct″ is available at www.provost.howard.edu. In
addition, only non-programmable calculators shall be allowed in the examinations. A student who violates
this policy will receive a grade of ″zero″ on that examination.
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GRADING IS DERIVED FROM THE FOLLOWING & ACCORDING TO UNZA REGULATIONS:
Examinations & Laboratory Exercises
Theory of Practical: Exam
Compounding: Exam
Laboratory Products
Maximum Mark Obtainable
%
Grade
40.0
40.0
20.0
100
90 – 100% = A
80 – 85% = B
70 – 75% = C
Below 70% = F
RELATIONSHIP OF COURSE COMPETENCIES TO NAPLEX
COMPETENCIES:
Upon Completion of the course, the student should be able to demonstrate the following
NAPLEX competencies:
Area 1 Assess Pharmacotherapy to Assure Safe and Effective
Therapeutic Outcomes (Approximately 56% of Test)
1.1.0 Identify, interpret, and evaluate patient information to determine the presence of a disease
or medical condition, assess the need for treatment and/or referral, and identify patient-specific
factors that affect health, pharmacotherapy, and/or disease management.
1.1.1 Identify and assess patient information including medication, laboratory, and
disease state histories.
1.1.2 Identify patient specific assessment and diagnostic methods, instruments, and
techniques and interpret their results.
1.1.3 Identify and define the etiology, terminology, signs, and symptoms associated with
diseases and medical conditions and their causes and determine if medical referral is
necessary.
1.1.4 Identify and evaluate patient genetic, and biosocial factors, and concurrent drug
therapy, relevant to the maintenance of wellness and the prevention or treatment of a
disease or medical condition.
1.2.0 Evaluate information about pharmacoeconomic factors, dosing regimen, dosage
forms, delivery systems and routes of administration to identify and select optimal
pharmacotherapeutic agents, for patients
1.2.1 Identify specific uses and indications for drug products and recommend drugs of
choice for specific diseases or medical conditions.
1.2.2 Identify the chemical/pharmacologic classes of therapeutic agents and describe
their known or postulated sites and mechanisms of action.
1.2.3 Evaluate drug therapy for the presence of pharmacotherapeutic duplications and
interactions with other drugs, food, and diagnostic tests.
1.2.4 Identify and evaluate potential contraindications and provide information about
warnings and precautions associated with a drug product’s active and inactive
ingredients.
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1.2.5 Identify physicochemical properties of drug substances that affect their
solubility, pharmacodynamic and pharmacokinetic properties, pharmacologic
actions, and stability.
1.2.6 Evaluate and interpret pharmacodynamic and pharmacokinetic principles to
calculate and determine appropriate drug dosing regimens.
•
1.2.7 Identify appropriate routes of administration, dosage forms, and pharmaceutical
characteristics of drug dosage forms and delivery systems, to assure bioavailability
and enhance therapeutic efficacy.
1.3.0 Evaluate and manage drug regimens by monitoring and assessing the patient
and/or patient information, collaborating with other health care professionals, and
providing patient education to enhance safe, effective, and economic patient outcomes.
•
1.3.1 Identify pharmacotherapeutic outcomes and endpoints.
1.3.2 Evaluate patient signs and symptoms, and the findings of monitoring tests and
procedures to determine the safety and effectiveness of pharmacotherapy. Recommend
needed followup evaluations or tests when appropriate.
1.3.3 Identify, describe, and provide information regarding the mechanism of adverse
reactions, allergies, side effects, iatrogenic, and drug-induced illness, including their
management and prevention.
1.3.4 Identify, prevent, and address methods to remedy medication non-adherence,
misuse, or abuse.
1.3.5 Evaluate current drug regimens and recommend pharmacotherapeutic
alternatives or modifications.
Area 2 Assess Safe and Accurate Preparation and Dispensing of
Medications (Approximately 33% of Test)
2.1.0 Demonstrate the ability to perform calculations required to compound, dispense, and
administer medication.
2.1.1 Calculate the quantity of medication to be compounded or dispensed; reduce
and enlarge formulation quantities and calculate the quantity or ingredients needed to
compound the proper amount of the preparation.
2.1.2 Calculate nutritional needs and the caloric content of nutrient sources.
2.1.3 Calculate the rate of drug administration.
2.1.4 Calculate or convert drug concentrations, ratio strengths, and/or extent of
ionization.
2.2.0 Demonstrate the ability to select and dispense medications in a manner that promotes
safe and effective use.
2.2.1 Identify drug products by their generic, brand, and/or common names.
2.2.2 Identify whether a particular drug dosage strength or dosage form is commercially
available and whether it is available on a nonprescription basis.
2.2.3 Identify commercially available drug products by their characteristic physical
attributes.
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2.2.4 Assess pharmacokinetic parameters and quality assurance data to determine
equivalence among manufactured drug products, and identify products for which
documented evidence of inequivalence exists.
2.2.5 Identify and provide information regarding appropriate packaging, storage,
handling, administration, and disposal of medications.
2.2.6 Identify and provide information regarding the appropriate use of equipment and
apparatus required to administer medications.
2.3.0 Demonstrate the knowledge to prepare and compound extemporaneous preparations and
sterile products.
2.3.1 Identify techniques, procedures, and equipment related to drug preparation,
compounding, and quality assurance.
2.3.2 Identify the important physicochemical properties of a preparation’s active and
inactive ingredients.
2.3.3 Identify the mechanism of and evidence for the incompatibility or degradation of a
product or preparation and methods for achieving its stability.
Area 3 Assess, Recommend, and Provide Health care Information that
Promotes Public Health (Approximately 11% of Test)
3.1.0 Identify, evaluate, and apply information to promote optimal health care.
3.1.1 Identify the typical content of specific sources of drug and health information for
both health care providers and consumers, and recommend appropriate resources to
address questions or needs.
3.1.2 Evaluate the suitability, accuracy, and reliability of clinical and pharmacoeconomic
data by analyzing experimental design, statistical tests, interpreting results, and
formulating conclusions.
3.2.0 Recommend and provide information to educate the public and healthcare professionals
regarding medical conditions, wellness, dietary supplements, and medical devices.
3.2.1 Recommend and provide health care information regarding the prevention and
treatment of diseases and medical conditions, including emergency patient care and
vaccinations.
3.2.2 Recommend and provide health care information regarding nutrition, lifestyle,
and other non-drug measures that promote health or prevent the progression of a
disease or medical condition.
3.2.3 Recommend and provide information regarding the documented uses, adverse
effects, and toxicities of dietary supplements.
3.2.4 Recommend and provide information regarding the selection, use, and care of
medical/surgical appliances and devices, self-care products, and durable medical
equipment, as well as products and techniques for self-monitoring of health status and
medical conditions.
Course Objectives and Terminal Competencies:
Terminal competencies are specified to give the instructor direction in projecting his/her
lectures. Behaviors of course competencies acquired in this course will enable the
student, at some later point, to be able to perform the following terminal competencies:
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(1). Counsel and advise patients on the proper use, safeguard and handling of
prescription and non-prescription (OTC) drug products, and home health care products.
(2). Demonstrate knowledge and skills in drug use in such areas such as compounding
and dispensing of medications.
(3). Communicate effectively with health-care professionals and patients to ensure the
provision of safe and effective pharmaceutical care.
(4). Provide instruction to health professionals regarding drug therapy.
(5). Demonstrate the ability to design and evaluate research in the identification and
solution of problems relevant to pharmaceutical care.
(6). Evaluate and interpret health science literature efficiently and accurately for
pharmaceutical care, research and education.
(7). Select, evaluate, and recommend appropriate drug product(s) and/or dosage
form(s) which are most useful for a disease state in an individual patient.
(8). Solve problems involving standard laboratory nomenclature such
as mg%, mg/dL, mg/ml and millimoles/L.
(9). Demonstrate the ability to solve dosage calculations involving
percentage weight-in-weight, weight-in-volume and volume-in-volume
preparations.
(10). Convert (when necessary) units in one system of measure into
units of another system of measure in order to calculate a dose.
(11). Determine medication dosage using a nomogram.
(12). Prepare appropriate quantities of medication from formulas
which are written for much larger or smaller quantities.
(14). Perform calculations involving density and specific gravity of liquids and solids.
(15). Demonstrate the ability to solve dosage calculations involving
percentage weight-in-weight, weight-in-volume and volume-in-volume
preparations.
(16).Demonstrate the ability to receive, interpret, evaluate prescriptions.
(17). Describe and discuss potential side effects of prescribed
medications and demonstrate proper communication of this
information to the patient or the patient’s care giver.
(18). Recognize the components of a properly written medication order.
(20). Recognize errors in prescribing and demonstrate the proper
procedure to resolve such errors as they occur.
(21). Interpret medication orders and determine what calculations if
any are required to prepare the order.
(22). Perform dosage calculations using units in the metric, apothecary
and avoirdupois systems of measure.
(23). Convert (when necessary) units in one system of measure into
units of another system of measure in order to calculate a dose.
Howard University College of Pharmacy
Learning Goals
Gather and organize patient information in order to identify ongoing or potential drug-related
problems and the root causes of the problems.
Interpret and evaluate pharmaceutical data and related information needed to prevent or resolve
medication-related problems.
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Plan and perform ongoing patient evaluation to identify additional drug-related problems.
Formulate, implement, and modify pharmaceutical care plans, including the recommendation of
pharmacotherapy
specific to patient needs and desired outcomes.
Document pharmaceutical [patient-centered] care activities in the patient’s medical record 1to facilitate
communication and collaboration among providers.
Display the attitudes, behavior and values required to render pharmaceutical [patient-centered] care.
Develop and manage a pharmacy and/or pharmacy practice; design and implement
medication preparation, distribution, use and control systems.
Provide drug information and education and promote public health.
Find, understand, analyze, evaluate and synthesize information and make informed, rational,
responsible, and ethical decisions.
Read, write, speak, listen, and use data, media and computers to effectively communicate with a
variety of audiences and different purposes.
Demonstrate sensitivity to and facility with personal values and ethical principles in professional and social
contexts.
Demonstrate a basic understanding of the strengths and problems of cultural diversity and the
historic responses of society, as they related to oneself and to others.
Effectively self-assess and satisfy learning needs on an ongoing basis.
Demonstrate effective interpersonal and intergroup behavior in a variety of situations and circumstances.
RELEVANT ACPE ACCREDITATION STANDARDS & GUIDELINES ON CULTURAL COMPETENCY
a
ACPE
ACPE Guideline 9.1
Ensuring that the curriculum addresses
patient safety, cultural appreciation,
health literacy, health care disparities,
and competencies needed to work as
a member of an inter-professional
team.
Accreditation Council for Pharmacy Education
b
Tool for Assessing Cultural Competence Training
RELATED COURSE
OBJECTIVES
Course Objective 1, 3, 6,
and 7
Activities in the Course related to the TACCT Domain
Objective 1 - A1(V) – Respect patient’s cultural beliefs (Health Literacy Educational Toolkit)
Objective 3 – K2(II) – Recognize patient’s healing traditions and beliefs (Objective Structured
Clinical Examination Practice Session)
Objective 6 – S1(IV) – Critically Appraise literature on disparities (Journal Article Review)
Objective 7 - A1(V) – Respect patient’s cultural beliefs (Health Literacy Educational Toolkit)
Remediation Policy:
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b
RELATED TACCT
DOMAIN
Objective 1 – A1(V)
Objective 3 – K2(II)
Objective 6 - S1(IV)
Objective 7 – A1(V)
The course coordinator will monitor students’ performance and identify those students who are in
academic difficulty. The nature of remediation will vary and will be based on individual instructor and may
include tutored/guided studies in areas of deficiencies and/or examination. Tutorial assistance will be
given through Center of Excellence (COE). The course coordinator will contact the students to attend
remediation procedures. It is incumbent upon the student to attend the remediation procedures and work
with the course coordinator in an effort to complete the course successfully.
Rules and Procedures for Conduct in the Laboratory
Cleanliness and neatness are essential in the Pharmacy Laboratory. It is your responsibility to keep
your laboratory desk work area, your balance and your equipment and utensils clean. Clean all dirty
apparatus before leaving the laboratory for the day.
Points will be deducted from your laboratory
report
grade if you leave your desk/area dirty.
To prevent contamination of reagents, do not return excess material to a stock bottle unless
advised to do so. DO NOT WASTE MATERIALS!!
All work is independent, unless directed otherwise.
Laboratory periods are to begin at the specified time and your presence at the pre-laboratory
discussion is required. Tardiness will not be tolerated.
There can be NO working in the laboratory other than at the scheduled times unless under the
supervision of the instructor, teaching assistants or the laboratory technician.
Professional attire is required for class. Students inappropriately dressed will be asked to leave the
class.
Students are required to wear long white laboratory coats at all times in the
laboratory.
Men are to wear slacks, shirts and neckties. (Please note; you will not be allowed to participate in
the
laboratory if you do not wear a necktie!)
Women are to wear slacks and blouses or dresses/suits.
The following attire is not permitted in the laboratory:
Caps, hats or other outdoor headgear
Sandals or other open-type footwear
Scrub suits
Blue jeans
NO SMOKING IS ALLOWED IN THE LABORATORY AT ANY TIME.
All preparations submitted for approval should be properly labeled. The following information
should be contained on each label:
Preparation No. and Completion date
Your last name and desk no.
Directions for use and/or name of preparation as specified
Instructor’s name as “Dr.”
Auxiliary labels, if needed, e.g. “Shake Well”, “External Use”, etc.
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COLLEGE OF PHARMACY AND PHARMACEUTICAL SCIENCES
HOWARD UNIVERSITY, WASHINGTON, D.C.
No IYour Name
Dat
Desk No.
Dissolve one teaspoonful in one pint
water and use as a vaginal douche.
Dr. J.A. Moore
Labels must be neatly typed, without strike-overs, misspellings, smudges,
fingerprints, etc.
Certain common areas of use in the laboratory will be assigned to two or more students
in each laboratory period to clean up and place in proper order at the end of each
laboratory. These assignments, and their nature, will be made at the beginning of each laboratory period.
You must provide for your own use in the laboratory the following:
Paper towels
Cloth towel
Safety gloves
Soap or detergent
Weight set (Compulsory)
White laboratory coat (long)
See your course plan for the grading system of laboratory work.
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LABORATORY SAFETY RULES
The laboratory is a potentially dangerous place. However, the risk can be minimized, if you follow safe
laboratory practices. Your safety depends on your knowledge of possible dangers and your adherence to
certain safety rules. The major hazards of the laboratory are the following:
A. Some compounds are toxic, biohazard, carcinogenic or corrosive. Exposure to
these chemicals can occur by inhalation or skin contact as well as by ingestion.
Some compounds or solvents are flammable. Their vapors can saturate the laboratory
atmosphere or linger on benches or in sinks.
Broken glass may cause cuts and exposure to hot glass or metal may cause severe burns.
Electrocution may occur when electric instruments are mishandled.
THE FOLLOWING SAFETY RULES MUST BE FOLLOWED AT ALL TIMES
No student is allowed to work in the laboratory unless a Faculty, a Laboratory Technician or a
Teaching Assistant (Graduate Student) is present.
Before doing any laboratory work, carefully read these safety rules and other safety information in
your laboratory exercises.
The laboratory should be treated as a professional pharmacy: Keep it neat and clean.
Wipe up spilled chemicals immediately.
Keep balances and work areas clean.
Do not throw powdered drugs, paper, greasy or waxy materials, or any insoluble waste material
into the sink. Wrap these items in a paper towel and discard them in the waste container
provided for this purpose.
Never pour unused solutions or other liquids back into the original container; pour
them into the waste disposal container in the hood.
Clean up all broken glassware immediately. Place all broken glassware in the broken glass
disposal carton.
Sandals or other open-type footwear may not be worn because of the hazard from broken glass and
spilled, caustic materials.
Smoking, eating or drinking in the laboratory is absolutely forbidden.
Eye protection must be worn at ALL times in the laboratory.
Avoid contact with chemicals on your skin. Wash immediately if chemicals come in contact with
your skin or clothing.
Know the location of fire extinguishers, safety showers, eyewash stations, and first aid kits, and
know how to use them.
Report any accident, however minor, to the instructor at once.
SUBMIT YOUR PREPARATIONS TO THE TEACHING ASSITANTS AND SIGN THE
LABORATORY PREPARATION SHEET BEFORE YOU LEAVE THE LABORATORY TO
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INDICATE THE PRODUCTS YOUR SUBMIT. NO GRADE WILL BE GIVEN TO A
PRODUCT SUBMITTED WITHOUT SIGNING THE PREPARATION SHEET.
17
Laboratory No. 1
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (87771-336-01)
SOLID DOSAGE FORMS - BULK AND DIVIDED POWDERS
Study Assignment and Background:
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7th Ed., Howard C. Ansel,
“Remington: “The Science and Practice of Pharmacy”, 20th Edition. “Lecture Notes on
Pharmaceutics”
Drugs may be dispensed in the powdered form for both oral and non-oral administration.
Powdered dosage forms may be dispensed either as “bulk powders” or “divided powders”.
Bulk powders are administered either:
as “dusts” from sifter-top containers, aerosol containers, or by “insufflators” (or powder
blowers); or
by subdividing at the time of use by measuring out portions by means of devices such as the
teaspoon, tablespoon, or special measuring devices.
Divided powders are divided and packaged by the manufacturer (or dispensing
pharmacist) as “powder papers (or chartulae)” or in foil or plastic envelopes.
In this laboratory exercise, both a “bulk powder” and a “divided powder” will be prepared. In
preparing all powders, one of the chief challenges to the pharmacist is to achieve homogeneity (or
uniformity) of the mixed powders whenever two or more ingredients are present. A “geometric
dilution” technique is the most common method of mixing used to best assure homogeneity in the
end product in the least possible time and with minimum effort.
Geometric dilution (or geometric mixing) - a process by which a small quantity of a drug in powdered
form is mixed with a larger quantity of diluent (or other drugs) to assure a homogeneous final mixture of
the drug using techniques that minimize time and effort.
The usual procedure in mixing by geometric dilution is to:
Weigh all of the powdered ingredients in the final product and set each aside.
Place the ingredient present in the smallest bulk volume in the mixing device, usually a mortar.
Take a portion of a second ingredient (from among those weighed and set aside) which is a
“visually-equivalent volume” to the ingredient already present in the mortar and add it to the
mortar and thoroughly mix. The second ingredient added should be the one present in the second
largest total volume in the formula.
Double the volume of the mixed ingredients in the mortar by adding another “visuallyequivalent volume” of the second ingredient. Mix in this second portion and continue this
“doubling” process with all the remaining ingredients until all are added and mixed.
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I-A. Douche Powder
Compound the following douche powder assuming a sensitivity of 1/10 grain for your balance and
maintaining a maximum weighing error tolerance of ± 5%.
-----------------------------------------------------------------------------------------------------------------Rx
Thymol
grains
Menthol
aa
1.5%
Methylbenzethonium chloride* 0.1%
5.0%
Zinc Sulfate, powder
grains
Boric Acid, powder, qs ad
grains =
100.0%
grains drug =
grains of
grains =
gr
M. ft. pulv.; dispense ii
Sig: Dissolve 1 tsp. in 1 qt. water and use as a vaginal douche.
-------------------------------------------------------------------------------------------------------------------*A 1:10 trituration of Methylbenzethonium chloride in lactose will be provided.
Procedure
Weigh out all ingredients and place them on labeled papers.
Place the thymol and menthol in a glass mortar and triturate until they form a eutectic
mixture (i.e. liquefy). Add the methylbenzethonium chloride trituration and thoroughly
mix.
Using geometric dilution techniques, add to the mortar with mixing, first the zinc sulfate,
followed by the boric acid.
Package the finished powder in a wide-mouth bottle and label with the appropriate
information including the patient usage instructions. Also, add the following supplemental
(auxiliary) strip” label
NOT TO BE TAKEN
BY MOUTH
Maximum percentage weighing error - by definition, the maximum weighing error in making a
weighing is given by:
Maximum Percentage
Weighing Error
= Sensitivity of the Balance Used x 100
Quantity Weighed
For each of the ingredients in the preceding prescription, calculate this error
using 1/10 grain as the sensitivity (SHOW ALL WORK):
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Maximum
Error
Ingredient
Percentage
Weighing
Thymol
Menthol
Methylbenzethonium Chloride Trituration
Zinc Sulfate
Boric Acid
Study Questions - Douche Powder Prescription
The “Sig” on the prescription on page 15 directs:
“Dissolve one teaspoonful in one quart of water and use as a vaginal douche”.
Assuming that the one teaspoonful of powder to be dissolved weighs about 5 grams, and that the final
quart of solution is about 1000 mL, calculate the final percentage and ratio strength of each formula
ingredient in the quart of final solution. SHOW ALL WORK.
% Strength
Ratio
Strength
Thymol
Menthol
Methylbenzethonium Chloride
Zinc Sulfate
Boric Acid
For the following questions, consult the Study Assignment and Background at the
beginning of the exercise:
What is the minimum diameter of a “very coarse powder”?
What are the five (5) purposes of particle size
analysis? a.
b.
20
c.
d.
e.
What is “micromeritics” ?
What is “comminution”?
For each of the ingredients in the douche formula listed on page 15, provide the therapeutic
indication in the formula. (Reference: “Handbook of Nonprescription Drugs”)
Therapeutic Indication in the Formula
Thymol
Menthol
Methylbenzethonium Chloride
Zinc Sulfate
Boric Acid
7. Give three (3) commercially-available douche powders (available over-the counter
(OTC products)) (Reference: “Facts & Comparisons”)
a.
b.
c.
21
I-B. Divided Powders (Powder Papers or “Chartulae”)
Compound the following prescription as indicated below:
---------------------------------------------------------------------------------------------------------Total Quantity needed in Rx
Rx
Belladonna Extract
15 mg
grams
Phenobarbital
25 mg
grams
Menthol*
0.5 mg
grams =
Lactose
400 mg
grams
drops of
M. ft. chart. #1.; D.t.d. # X
Sig: Take 1 pwd. 1 h. a.c. in aq.
-------------------------------------------------------------------------------------------------------------------*Note: the menthol is intended as a flavoring agent and will be provided as a 10% w/v
alcoholic solution in a dropper bottle which delivers 40 drops/mL.
Procedure
Calculate the total amount of each ingredient needed to compound the above prescription and
record this data above.
Weigh the solid ingredients and place on labeled weighing papers.
Mix the belladonna extract and phenobarbital in a glass mortar by trituration. Then, using
geometric dilution, mix in about one-fourth of the lactose; add the drops of alcoholic menthol
solution and thoroughly mix. Complete the mixing by adding the rest of the lactose by geometric
dilution.
Weigh out the proper amount of mixture for each powder paper and fold the papers as
demonstrated in the laboratory and illustrated in the attachment on the following page.
Weight of mixture in each powder paper =
grams
Package the powder papers in a hinged box and label the box with the proper directions.
-----------------------------------------------------------------------------------------------------------------Maximum Percentage Weighing Errors - Using the definition on page 15, calculate the maximum
percentage weighing error for each ingredient in the above prescription assuming a sensitivity of 6 mg
for your balance (SHOW ALL WORK):
22
Maximum Percentage Weighing Error
Belladonna Extract
%
Phenobarbital
%
Lactose
%
Mixture in one powder paper
%
The Packaging of Divided Powders
Packaging Divided Powders-Specially manufactured paper and boxes are available
for dispensing divided powders.
Powder Papers-Four basic types of powder papers are available.
Vegetable parchment, a thin semiopaque moisture-resistant paper
White bond, an opaque paper with no moisture resistant properties.
Glassine, a glazed transparent moisture-resistant paper.
Waxed, a transparent waterproof paper
Hygroscopic and volatile drugs can be protected best by use of a waxed paper, double
wrapped with a bond paper to improve the appearance of the completed powder.
Parchment and glassine papers offer limited protection for these drugs.
A variety of sizes of powder papers are available. The selection of the proper size depends on
the bulk of each dose and the dimensions of the powder box required to hold the number of
doses prescribed.
Powder Boxes- Various types of boxes are supplied in several sizes for dispensing divided
powders. The hinged-shoulder boxes shown in the Figure 1 are the most popular and have
the advantage of preventing the switching of lids with the directions for use when several
boxes of the same size are in the same home. The prescription label may be pasted directly
on top of the lid or inside the lid.
Folding the Paper
Place the paper flat on a hard surface and fold toward you a uniform flap of about 1/2 inch of the long
side of the paper. To ensure uniformity of all of the papers, this step should be performed on all the
required papers concurrently, using the first folded paper as the guide (Figure A).
With the flap of each paper away from you and pointing upward, place the weighed or divided amount of
powder in the center of each paper.
Being careful not to disturb the powder excessively, bring the lower edge of the paper upward, and
place it proximate to the crease of the flap (Figure B).
Grasp the flap, press it down upon the tucked-in bottom edge of the paper and fold again toward you
an amount of paper equal to the size of the original flap (1/2 inch) (Figure C).
Pick the paper up with the flap upward and facing you, being careful not to disturb the position of the
powder, and place the partially folded paper over the open powder box (to serve as the container) so that
the ends of the paper extend equally beyond the sides (lengthwise) of the open container. Then, press
the sides of the box slightly inward and the ends of the paper gently downward along the sides of the box
to form a crease on each end of the paper. Lift the paper from the box and fold the ends of the paper
along each crease sharply so that the powder cannot escape (Figure D).
The folded papers are then each placed in the box so that the double-folded flaps are at the top,
facing the operator, and the ends are folded away from the operator (Figure E, below).
23
Papers folded properly should fit snugly in the box, have uniform folds, and should be of uniform length
and height. There should be no powder in the folds, and none should be
capable of escape with
moderate agitation. Powder boxes, which are generally pasteboard and of the hinged type, should close
easily without coming in contact with the tops of the papers.
Figure 1. Folding Powder Papers.
A
24
B
C
Study Questions-Powder Prescription
The usual “adult” dose of Belladonna Extract is 15 mg. If this preparation was to be administered
to a 10 year old, 75 pound boy, what would the proper dose be for the child with a body surface
area of 93 m2. (Use the body surface area method for the calculation. SHOW ALL WORK.
Define the term hygroscopic.
What type of powder paper protects hygroscopic and volatile drugs best?
Is the “block-and-divide” method of obtaining the individual quantities of mixture for each powder
paper acceptable for use in this prescription? (Check one)
Yes
No
Justify your answer.
Belladonna Tincture and Belladonna Extract are both official in the USP-NF. Which of these
preparations is:
A liquid:
A solid:
How does the potency (or concentration of active ingredients) of Belladonna Extract compare with
Belladonna Tincture?
The most potent
is: Your reason:
25
What is the therapeutic or pharmaceutical use of each of the ingredients in the prescription.
Therapeutic Indication in the Formula
Belladonna Extract
Phenobarbital
Lactose
8. Complete the following table with the usual adult dose of Phenobarbital.
(Remington: “The Science and Practice of Pharmacy; 19th Ed., pp. 1164-1165)
Usual Adult Dose of Phenobarbital
Oral Sedative
Hypnotic
Anticonvulsant
Usual range of dose
26
Product Evaluation
I-A. Bulk Powder
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Inconsistent mixture
Improper amount
Unclean bottle
Powder around the neck of the bottle
Other
10 Points
Points
total points for product
*Results in zero points for the entire product.
27
Product Evaluation
I-B. Chartulae
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Charts placed incorrectly in box
Unevenly folded
Incorrect number of charts
Incorrect weight
Other
10 Points
Points
total points for product
*Results in zero points for the entire product.
28
Laboratory #1 - Bulk and Divided Powders
Grade Sheet
Product Points
I-A
I-B
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
29
Signature of Instructor:
Laboratory No. 2
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (87771-336-01)
HARD GELATIN CAPSULES
Study Assignment and Background:
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7th Ed., Howard C. Ansel
Remington: “The Science and Practice of Pharmacy”, 20th Ed.,
The purpose of this laboratory exercise is to:
develop proficiency in formulation and compounding of capsules as solid dosage forms.
General Discussion
Two piece hard-gelatin capsules come in eight actual sizes as illustrated below and the approximate
capacities are also shown in the Table below:
Table - Capacity of Empty Capsules
APPROXIMATE CAPACITY OF EMPTY CAPSULES
No.
000
00
0
1
2
3
4
5
Quinine Sulfate
grs. 10
6
5
31/2
3
2
11/2
1
Sodium Bicarbonate
grs. 22
15
11
8
6
5
4
2
Acetylsalicylic Acid
grs. 16
10
8
5
4
3
21/2
11/2
Bismuth Subnitrate
grs. 28
20
14
10
8
6
4
2
Actual Sizes of Empty Gelatin Capsules
The data in the Table above is taken from the label of a box containing empty gelatin
capsules (manufactured by Eli Lilly Co.) and shows the approximate capacity of each size
of capsule for four different drugs. It is noted that this particular set of four drugs vary in
density (from quinine sulfate to bismuth subnitrate) by a factor of almost three, i.e., a No.
000 capsule will hold about 10 grains of quinine sulfate but about 28 grains of bismuth
subnitrate. It is also noted that the smallest capsule (size No. 5) holds only about one grain
of the lightest listed drug (quinine sulfate) whereas the largest capsule (size 000) hold 28
grains of the heaviest listed drug (bismuth subnitrate). This Table reveals, therefore, that
the pharmacist has considerable latitude available when selecting a capsule size that is
appropriate for holding a given drug or drug combination.
30
In this laboratory exercise, three different drug formulas will be filled into
capsules with each formula representing a somewhat different problem in capsule
selection and/or filling.
II-A. Capsules
Fill the following prescription as indicated below:
---------------------------------------------------------------------------------------------------------Rx
Aspirin
grs. v
M. ft. cap. # i; DTD # xii caps
Sig: i cap. q 4 h. prn pain
--------------------------------------------------------------------------------------------------------This prescription represents the simplest possible problem in filling capsules since:
only a single drug is present;
the drug is listed on the “chart” on the capsule box, i.e., on the chart incorporated into the Table
shown earlier;
the amount of drug is exactly the same quantity as listed on the “chart” on the capsule box for a
particular size capsule.
Procedure
1. Weigh out enough aspirin powder to fill one extra capsule and, using the technique
for capsule filling demonstrated in class, fill twelve (12) No. 1 capsules with 5 grains of aspirin.
(Be sure to check the fill weights of the capsules by weighing and also remember to place an
empty No. 1 capsule on the right weight pan to “cancel” out the weight of the capsule shell of the
capsule being filled.) Note: The following is from “Prescription Pharmacy”, Sprowls, 1963:
The attraction of gelatin for moisture requires the pharmacist to observe care in handling a
capsule. A trace of moisture on the capsule causes a sticky surface to which dry material
adheres. The best method of protecting the capsule from moisture and finger prints is to
wear finger cots or rubber gloves.
Before compounding in the prescription area, a pharmacist should wash his/her
hands. Clean hands are especially important when the dosage form is manually
touched. With open prescription departments, the patron is able to observe the
compounding of his/her prescription. It enhances the public image of the
pharmacist when the patient sees the pharmacist washing his/her hands,
wearing finger cots and compounding under sanitary conditions.
31
Another method by which capsules may be kept free from moisture during compounding is
to wash the hands thoroughly, dry and keep the fingers dry by friction against a towel
before each capsule is handled. The towel should be stripped through the clenched fingers
until a clearly perceptible heat is felt.
A third method is to use the base of one capsule as a holder for other bases during the
filling procedure. This minimizes contact of the fingers with the capsule.
Regardless of how careful the filling operation has been, some traces of material will be
found on the outside of the filled capsule. This may be removed by rolling the capsule
between the folds of a cloth or by shaking them in a cloth which has been gathered into the
form of a bag.
Clean the capsules with a dry cloth or paper towel, then place in an appropriate sized capsule
vial.
Prepare a label for the vial by placing the translated “Sig” on the label together with other
pertinent information as outlined in the General Laboratory Procedure. (Note: Since labels do not
adhere well to plastic containers, cover the label with a strip of transparent tape.)
II-B. Capsules
Fill the following prescription as indicated below:
---------------------------------------------------------------------------------------------------------Rx
Ephedrine sulfate
30 mg.
Ft. cap. # i; DTD # x
Label: Ephedrine Sulfate, 30 mg
--------------------------------------------------------------------------------------------------------In this prescription, a simple drug ingredient is present (as in the preceding prescription) but filling
the prescription presents some greater complexity since:
the drug per capsule (30 mg.) is a smaller quantity than will properly fill even a No. 5 capsule,
the smallest available capsule size; and
the drug is not listed on the “chart” on the capsule box, i.e., in the Table shown earlier.
It will be necessary to combine the drug with a suitable “diluent” or “bulking” agent to increase the
formula amount (or volume) to a level which can fill a capsule. The most common diluent for capsule
filling is lactose since it has both a low chemical reactivity and is physiologically non-toxic. After
deciding to use lactose as the diluent, the question still remains as to how much lactose to use. The
amount of lactose, plus the drug, should be adequate to fill one of the eight capsule sizes available.
Lactose is not listed in the Table of drugs versus capsule sizes, but one can “guess” that its density is
probably somewhere between the lightest and heaviest drugs listed. Guided by such a “guess”, one
could expect that a No. 2 capsule, for example, might hold from 4 to 6 grains (260 to 390 mg) of
lactose.
32
(Alternatively, the pharmacist can “calibrate” the capsules with lactose by filling at least one of each with
lactose to more precisely determine their fill capacity for lactose).
Finally, the question of handling and filling convenience of capsules versus administration ease for the
patient can be considered. Although patients would find the smallest capsule the easiest to swallow,
very small size capsules are rather hard for the pharmacist to hold and fill by the “punch” method.
Consequently, “intermediate” size capsules, e.g., Nos. 0, 1, 2, and 3 are the most popular for use when
other factors permit. In this case, we will attempt to achieve a fill volume that will permit use of such an
intermediate size capsule. We will arbitrarily decide to use 300 mg of lactose per capsule (to be
combined with the 30 mg of ephedrine sulfate). This will provide a fill weight of 330 mg per capsule
which should fit into one of the intermediate capsule sizes acceptably.
Procedure
1. Weigh out enough ephedrine sulfate to prepare one extra capsule.
List this total quantity here:
gm.
Weigh out 300 mg of lactose for each capsule, i.e., enough for one extra
2. capsule.
List this quantity here:
gm.
Mix the ephedrine sulfate and lactose by geometric dilution in a glass mortar.
Choose a capsule size (by experimental trial) that will nicely hold the 330 mg of capsule
formulation required for each capsule.
List this capsule size here:
Fill the capsules, checking the fill weight by weighing; clean the capsules, and package in a vial.
Label the vial and place transparent tape over the label.
II-C. Capsules
Fill the following prescription as indicated below:
33
---------------------------------------------------------------------------------------------------------Rx
Amount needed for xi capsules
A. S. A.
1.95 gm
gm
Acetaminophen
1.00 gm
gm
Caffeine
0.20 gm
gm
Tripelennamine HCl 0.25 gm
gm
M. et ft. pulv.; div. et ft caps No. 10
Sig: i cap. q. 6 h. p.r.n. headache and cold symptoms.
--------------------------------------------------------------------------------------------------------This prescription is more typical of “real” capsule prescriptions which pharmacists compound than
either of the previous prescriptions because:
the formula is for a combination of drugs rather than a single drug entity; and
the weight of the drugs alone is sufficient to fill a capsule, i.e., no diluent need be added to
achieve satisfactory bulk or volume.
Procedure
Weigh each ingredient in a quantity sufficient for one extra capsule and set each quantity aside
on a labeled papers.
Mix the ingredients, secundum artem, i.e., by geometric dilution.
Calculate the total weight of the contents of each capsule and record the weight below:
gm
From the available capsule sizes, select the one which best holds the formula weight
determined in step 3 (above). Fill the capsules with the proper weight of the formulation,
checking the fill amount by weighing.
Clean the capsules, package them in a suitable sized vial. Label the vial, including the
translated “Sig”, with the appropriate information and place transparent tape over the label.
List this capsule size here:
34
Study Questions - Capsules
What is the principal therapeutic indication for the following:
Therapeutic Indication in the formula
Ephedrine Sulfate
Acetaminophen
Tripelennamine
What is the animal product from which hard gelatin capsules are made?
What percent of moisture is normally found in hard gelatin capsules?
What substance is added to the formula to render capsules opaque?
What substance is used to fuse the two capsule halves together to make a one-piece capsule which
is “tamper evident”?
What is the purpose of surfactants in industrial formulas?
35
According to references given to you, what is the name of the machine used in industry that “cleans
and polishes” hard-filled capsules?
Aspirin is indicated for various conditions. List the therapeutic indication and the usual adult dose.
(Remington: “The Science and Practice of Pharmacy”, 19th ed., p. 1209.)
Therapeutic Indication
Usual Adult Dose
1.
2.
3.
What does the abbreviation A.S.A. stand for?
What is the usual adult dose of Acetaminophen. (Remington: “The Science and Practice of
Pharmacy”, 19th ed.)
If the patient took the capsules in Rx II-C, around the clock, what is the daily dose of each
ingredient? (Express the results in milligrams.) SHOW ALL WORK.
Ingredient
A.S.A.
Acetaminophen
Caffeine
Tripelennamine HCl
36
Daily Dose (in mg.)
The Pharmacist has decided to prepare a bulk amount of the capsules in R x II-C. When checking the
stock of ingredients, she finds that she has 1 kilogram of A.S.A., 500 grams of caffeine and an unlimited
amount of the other ingredients. How many capsules can the pharmacist make? (SHOW ALL WORK.)
According to the table “Capacity of Empty Capsules”, what size capsule would you
use for 5 grains of:
Quinine Sulfate
Sodium Bicarbonate
Acetylsalicylic Acid
Why would the same weight of different ingredients fit in various size capsules?
A Pharmacist opened a new bottle of 250 g of Aspirin powder to prepare R x II-A. If she followed the
procedure listed, how many milligrams of Aspirin powder would be left after filling this prescription?
(SHOW ALL WORK).
MORE INFORMATION ON ENCAPSULATION PROCESS
Two general methods of encapsulation of powders are commonly used today. They are
individual hand filling and capsule machine filling. We have discussed the hand filling.
Capsule Machine Filling
A number of manually operated capsule filling devices are commercially available for
filling up to 50, 100, or 300 capsules at a time (see Figure below). These machines can
be used for preparing smaller quantities by blocking off unused holes with an index
card. The principle of its operation will be shown to you in the laboratory.
Using these machines requires a careful determination of the capsule formulation. The
powder is blended as previously discussed. Empty gelatin capsules are placed into the
device so that the cap is on top. The machine is worked to separate the base from the
cap, and the portion of the machine holding the caps is removed and set aside. The
capsule bases are allowed to drop into place so that the top of the base is flush with the
working surface. The powder mix is then spread over the working surface. A plastic
spatula can be used to spread the powder evenly into the capsule bases.
Alternatively, the machine can be tapped to spread the powder and drop it down into the
capsule bases. A small device consisting of several pegs can be used to tamp the
powder into the capsule bases gently and evenly. Any remaining powder is then spread
evenly over and into the capsule bases, followed by addi-tional tamping. These
procedures are repeated until all of the powder is in the capsules. The portion of the
37
machine holding the capsule caps is then fitted over the machine and fixed in place.
The filled capsules are capped, removed, dusted with a clean cloth, and packaged.
Selection of the Right Capsule Size: More Information
Eight different sizes of gelatin capsules are generally used for human consumption,
ranging from the smallest, No. 5, through the largest, No. 000. The numerical
designation for a capsule is arbitrary and does not indicate the capsule’s capacity. The
capacity of a capsule depends upon the density and characteristics of the powders it
contains. The capsule size offers only a relative volume designation. Examples of the
weights of materials that can be held by capsules are shown in Table below:.
Different Powder Weights (in milligrams) for Various Sizes of Capsules
Capsule
Size*
Powder Material 5
4
3
0 00
000
2
1
Acetaminophen 130 ‘180 240 310 420 540 750 1100
Aluminum
hydroxide
180 270 360 470 640 820 1140 1710
Ascorbic acid
‘130 220 310 400 520 700 980 1420
Aspirin
65
130 195 260 325 490 650 975
Bismuth
subnitrate
120 250 400 550 650 800 1200 1750
Calcium
carbonate
120 200 280 350 460 600 790 1140
Calcium lactate 110 160 210 260 330 460 570 800
Cornstarch
130 200 270 340 440 580 800 1150
Lactose
140 210 280 350 460 600 850 1250
Quinine sulfate 65
97
130 195 227 325 390 650
Sodium
bicarbonate
130 260 325 390 510 715 975 1430
*Depending upon the actual powder density.
Veterinary compounding has also been increasing dramatically in recent years.
Capsules for veterinary use are available in sizes designated as No. 10, No. 11, and
No. 12, with capacities of 1 oz, 1/2 oz, and 1/4 oz, respectively.
38
Generally, capsules can be used to encapsulate between 65 and 1000 mg of powdered
material. Capsule selection is usually a simple matter. Some patients may have difficulty
swallowing the larger capsules (No. 00, No. 000), but others, especially the elderly, may
find the smaller capsules (No. 5, No. 4) hard to handle. The capsule size selected
should be slightly larger than is needed to hold the powder, since additional powder will
be added, as discussed below, to produce a full capsule. There are ways to
compensate for the handling and swallowing problems. If the active drug powder bulk is
small, more diluent can be added to increase the size of a capsule for handling
convenience. If the powder bulk is too large, the total amount can be divided into two
smaller capsules that are easier to swallow.
The Rule of Sixes is an interesting technique for the extemporaneous filling of
conventional hard gelatin capsules. The method is as follows:
1.Set up six “6s.”
6
6
6
6
6
6
2. List the capsule
size.
0
1
2
3
4
5
3. Subtract values in step 2 from those in step 1 to determine the
average fill
weight in grains.
6
5
4
3
2
1
4. Convert fill weight to grams (1 grain =
0.26
0.13 0.06
0.065 g).
0.195 0
5
0.390 0.325 0
Determine fill volume in milliliters (see Table below).
0.67 0.50 0.37 0.30 0.21 0.12
6. Calculate and list average capsule fill density (divide weight values in step 4 by
volume values in step 5).
0.58 0.65 0.70 0.65 0.62 0.54
As can be seen, the average fill density of the capsules is about 0.62 g/mL.
Table below gives the bulk densities of typical active drugs and excipients. The bulk
densities for these materials range between 0.4 and 0.8 g/mL, with an average of 0.6
g/mL, which is close to the fill density of empty, two-piece, hard gelatin capsules;
therefore, it forms the basis for the Rule of Sixes.
Approximate Capacities of Capsules (in milliliters)
Human Sizes
5
4
3
2
1
0
00
000
Veterinary Sizes
10
11
12
Capacity
0.12
0.21
0.30
0.37
0.50
0.67
0.95
1.36
Capacity
30
15
7.5
39
40
Encapsulation Using Hand Filling and Capsule Machine Filling
Students will work in groups as announced previously.
Each group will fill capsules using capsule machine filling and hand filling
Materials/equipments needed to prepare capsules:
Both active and inactive ingredients
Capsule machine parts
Mortar and Pestle
Spatulas
Weighing paper
Balances for weighing
Empty gelatin capsules
Pusher
Spreader
Paper towel
Vials
Label
Group 1: Using the capsule filling machine
Compound the following Rx :
Prescription #1
Amoxicillin 125mg capsules
Lactose 265mg
Dispense: #100
Sig: take one cap po q8h
Use Capsule #1
Show your calculations:
Group 1: Using hand filling method
See Exercise II-C Capsules
Group 2 : : Using the capsule filling machine
Prescription #1
Progesterone/Testosterone 50/1 mg capsules
Lactose—158mg
Dispense: #100
Sig: 1 capsule po qd ud
Use Capsule #3
Show your calculations
Group 2: Using hand filling method
41
See Exercise II-C Capsules
Group 3: Using the capsule filling machine
Prescription #1
Biest: Estriol/Estradiol 2.5mg (80:20)
Progesterone 25mg
DHEA 25mg
Lactose—158mg
Dispense : #100
Sig: I cap po qd ud
Use Capsule #3
Show all your calculations
Group 3: Using hand filling method
See Exercise II-B Capsules
Group 4: Using the capsule filling machine
Prescription #1
Piroxicam 3.5mg capsule
Lactose—206mg
Dispense #100
Sig: 1 cap po bid
Use Capsule #3
Show all your calculations
Group 4: Using hand filling method
See Exercise II-B Capsules
Group 5: Using the capsule filling machine
Prescription #1
ASA-200 mg
Acetaminophen—300mg
Caffine—35mg
42
Tripelennamine—40mg
Lactose---65mg
Dispense #100
1 cap po tid cf prn
Use Capsule #00
Show all your calculations.
Group 5: Using hand filling method
See Exercise II-B Capsules
Comment briefly (not more than three sentences) on the purpose of
each ingredient in capsules prepared using the capsule filling method
Product Evaluation
II-A. Aspirin Capsules
Label
Incorrect Sig
Type overs/erasers
43
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Dull
Grainy
Improper size capsule
Incorrect number of capsules
Other
Points
Points
total points for product
*Results in zero points for the entire product.
44
Product Evaluation
II-B. Ephedrine Sulfate Capsules
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Dull
Grainy
Improper size capsule
Incorrect number of capsules
Other
Points
Points
total points for product
*Results in zero points for the entire product.
45
Product Evaluation
II-C. Capsules
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Dull
Grainy
Improper size capsule
Incorrect number of capsules
Other
Points
Points
total points for product
*Results in zero points for the entire product.
46
Laboratory #2 - Hard Gelatin Capsules
Grade Sheet
Product Points
II-A
II-B
II-C
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
47
Signature of Instructor:
48
Laboratory No. 3
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (8771-336-01)
AQUEOUS SOLUTIONS AND SYRUPS
Study Assignment and Background:
“Pharmaceutical Dosage Forms and Drug Delivery Systems by Howard C. Ansel, et. al.
The purposes of this set of laboratory exercises are to:
develop skills in preparing and using stock solutions to provide ingredients for
solution-type pharmaceuticals; and
(2) prepare a representative variety of aqueous solutions and pharmaceutical syrups
to
better understand their properties.
-----------------------------------------------------------------------------------------------------------------Although in a physical sense, a “solution” is any homogenous mixture in which one substance
(either in the form of a gas, liquid, or solid) is dissolved in a liquid, in pharmacy, some “solutions” are
given other “pharmaceutical” names such as syrups;, elixirs, spirits; glycerites, etc. However, the
term “solution” is still applied to many pharmaceuticals and, although not always employing water as the
solvent, they usually do. In these exercises, several different types of aqueous solutions will be prepared
to illustrate some of the variety encountered in this type of pharmaceutical preparation.
----------------------------------------------------------------------------------------------------------------III-A. Solution
Rx
Potassium Permanganate Solution
90 mL
M. ft. soln. of such strength that 5 mL diluted to 500 mL gives a 1:5000 soln.
Sig: Add 1 tsp to 1 pt. aq. & use as a wash as directed.
-------------------------------------------------------------------------------------------------------------Procedure
1. Calculate the amount of KMnO4 needed to compound this prescription and enter your weight
here:
gm.
Weigh the KMnO4 and place in a glass mortar.
Dissolve the KMnO4 in increments with water by adding 15-20 mL portions of distilled water to
the mortar, stir thoroughly but lightly with the pestle until saturation is approached, then carefully
decant this portion into a prescription bottle, retaining the residual, undissolved KMnO 4 in the
mortar. To this residual solute, add another portion of water and repeat the above process until
all the solute is dissolved; then bring to the final volume by adding distilled water to the bottle.
Affix the cap and invert several times to insure uniformity.
49
[Note: The dissolution procedure provided above is useful in this case since the solution quickly
becomes so deeply colored that the presence of undissolved KMnO4 cannot be observed through
the solution. Yet it is very important that all of the solute be in solution before it is dispensed to the
patient for use. Therefore, the given step-wise procedure permits a periodic checking of the
completeness of the dissolution process at the time each portion is decanted. In case any residue
remains at the last decantation, portions of the solution must be returned to the mortar to effect
further dissolution.]
Label the prescription in accordance with the general procedural instructions including the
patient usage instructions. Include the following supplemental label:
FOR EXTERNAL USE ONLY
Study Questions - Solutions
What caution in handling KMnO4 is given in the U.S.P.-N.F. monograph?
Provide three (3) uses of KMnO4 solutions and the % strength in which they are used.
Potassium Permanganate Solution
Use
%
Strength
1)
2)
3)
In preparing a solution of potassium permanganate, three (3) 300 mg tablets are
dissolved in 1 pint of purified water. Use the exact volume of a pint.
What is the percentage strength (w/v) of the solution?
50
What is the ratio strength of the solution?
Can this ratio strength be used as a wet dressing? (Check
one) Yes
No
Explain:
---------------------------------------------------------------------------------------III-B. Solution
The U.S.P.-N.F. provides the following information for Peppermint Water N.F. and three (3) methods of
preparation:
Peppermint Water N.F.
Peppermint Water is a clear, saturated solution of Peppermint Oil in Purified Water prepared by one
of the processes described under Aromatic Waters (see Pharmaceutical Dosage Forms <1151>).
Waters - Aromatic
Aromatic waters are clear, saturated aqueous solutions (unless otherwise specified) of
volatile oils or other aromatic or volatile substances. Their odors and tastes are similar
to those of the drugs or volatile substances from which they are prepared, and they are
free from empyreumatic and other foreign odors. Aromatic waters may be prepared by
distillation or solution of the aromatic substance, with or without the use of a dispersing
agent.
Aromatic waters may be prepared by one of the following processes:
Distillation Method - Place the odoriferous portion of the plant or drug from which the aromatic
water is to be prepared in a suitable still with sufficient purified water, and distill most of the
water, carefully avoiding the development of empyreumatic odors through the charring or
scorching of the substances. Separate the excess of oil from the distillate, and preserve or use
the clear water portion, filtering if necessary.
Solution Method - Shake 2 g or 2 mL (if a liquid) of a volatile substance (suitably comminuted if a
solid) with 1000 mL of purified water in a container of sufficient capacity, and repeat the shaking
several times during a period of about 15 minutes. Set the mixture aside for 12 hours or longer,
filter through wetted filter paper, and add purified water through the filter to make the product
measure 1000 mL.
Alternative Solution Method - Thoroughly incorporate the volatile oil (or the suitably comminuted
volatile solid) with 15 g of talc or with a sufficient quantity of purified siliceous earth or pulped
filter paper. Add 1000 mL of purified water, and thoroughly agitate the mixture several times
during ten minutes. Then filter the mixture, returning the first portions, if necessary, to obtain a
clear filtrate, and add purified water through the filter to make the product measure 1000 mL.
Aromatic waters require protection from intense light and excessive heat. -----------------------------------------------------------------------------------------------------------
51
Prepare the following:
III-B. Solution
Rx
Peppermint Water, N.F. XVII
90 mL
Label: Peppermint Water, N.F. XVII
------------------------------------------------------------------------------------------------------------Procedure:
Use the Alternative Solution Method provided on page 47 using talc. List the quantities of
ingredients needed for 90 mL of Peppermint Water:
Peppermint Oil
mL =
Talc
gm
Purified Water
mL
drops*
*Available in dropper bottles which deliver 45 drops/mL.
2. Package the product in a 3-oz bottle and label as indicated.
Study Questions - Solutions
What two (2) purposes are served by the talc in the Alternative Solution Method of making
aromatic waters?
a.
b.
Why are substances such as MgCO3 and Ca3(PO4)2 unsuitable for use as distributing agents
in preparing aromatic waters?
What is purified siliceous earth?
52
Why are aromatic waters best stored in:
(a) Air-tight containers?
(b) Light-resistant containers?
(c) Containers maintained at room temperature (rather than in the refrigerator, for example)?
5. What is an empyreumatic odor?
53
Syrup
Note: The following is from “Remington’s Pharmaceutical Science”, Volume XVIII.
Syrups are concentrated solutions of a sugar such as sucrose in
water or other aqueous liquid. When purified water alone is used
in making the solution of sucrose, the preparation is known as
syrup, or simple syrup. In addition to sucrose, certain other
polyols, such as glycerin or sorbitol, may be added to retard
crystallization of sucrose or to increase the solubility of added
ingredients. When the aqueous preparation contains some
added medicinal substance, the syrup is called a medicated
syrup. A flavored syrup is one which is usually not medicated,
but which contains various aromatic or pleasantly flavored
substances and is intended to be used as a vehicle or flavor for
prescriptions. Flavored syrups offer unusual opportunities as
vehicles in extemporaneous compounding and are readily
accepted by both children and adults. Because they contain no
or very little alcohol, they are vehicles of choice for many of the
drugs that are prescribed by pediatricians. Their lack of alcohol
makes them superior solvents for water-soluble substances.
In manufacturing syrups the sucrose must be carefully
selected and a purified water, free from foreign substances
and clean vessels and containers must be used. The
operation must be conducted with care so as to avoid
contamination, if the products are to be stable preparations.
It is important that the concentration of sucrose approach but
not quite reach the saturation point. In dilute solutions sucrose
provides an excellent nutrient for molds, yeasts, and other
microorganisms. In concentration of 65% by weight or more,
the solution will retard the growth of such microorganisms.
However, a saturated solution may lead to crystallization of a
part of the sucrose under conditions of changing temperature.
Study Questions - Syrup
What is the synonym for Syrup?
Knowing the specific gravity of Syrup, N.F., is 1.313, what is the weight of one gallon of syrup? Use
the exact volume of one gallon in the calculation.
Answer
Microbial growth of Syrup, N.F., is concentration-dependent. Explain.
54
How much sucrose is required to make 250 ml of Syrup such that the concentration is sufficient to
retard the growth of microorganisms.
Answer
The following is the formula for Ferrous Sulfate Syrup, U.S.P.XXII:
Ferrous Sulfate................................
40 gm
Citric Acid, hydrous.........................
2.1 gm
Peppermint Spirit.............................
2.0 mL
Sucrose............................................
850 gm
1000
mL
Purified Water, qs ad.......................
What type of Syrup is “Ferrous Sulfate Syrup, U.S.P.”?
--------------------------------------------------------------------------------------------------------------------
III-C. Syrup
Prepare 90 mL of Acacia Syrup, N.F XVI.:
N.F. Formula
Acacia, granular or powdered
Sodium Benzoate
Vanilla Tincture*
Sucrose
Quantity for 90 mL
100 gm
gm
1 gm
gm
5 mL*
800
gm
mL =
gm
Purified Water, a sufficient quantity
to make
1000 mL
---------------------------------------------------------------------------------------------------*Available in dropper bottles which delivers 25 drops/mL.
55
mL
Procedure:
[From the N.F. XVI.]
Mix the acacia, sodium benzoate and sucrose; then add 51 mL of purified water and mix well.
Heat the mixture on a steam bath until solution is completed.
When cool, remove the scum on the top of the mixture; add the vanilla tincture and sufficient water
to make the product measure 90 ml.
Strain, if necessary.
Package the syrup in a 3-oz. prescription bottle and label:
Acacia Syrup, N.F. XVI
Study Questions - Syrup
Why is Sodium Benzoate included in this preparation?
What is the solubility of Sodium Benzoate:
in water
in alcohol
Complete the following table.
Syrup
Cherry Syrup
Wild Cherry Syrup
Syrup
Acacia Syrup
56
Use
Product Evaluation
III-A. Potassium Permanganate Solution
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
KMnO4 not completely dissolved
Other
Points
Points
total points for product
*Results in zero points for the entire product.
57
Product Evaluation
III-B. Peppermint Water
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Cloudy solution
Other
Points
Points
total points for product
*Results in zero points for the entire product.
58
Product Evaluation
III-C. Acacia Syrup
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Unfiltered
Consistency too thin
Other
Points
Points
total points for product
*Results in zero points for the entire product.
59
Laboratory #3 - Aqueous Solution and Syrups
Grade Sheet
Product Points
III-A
III-B
III-C
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
Signature of Instructor:
60
Laboratory No. 4
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (8771-336-01)
NON-AQUEOUS SOLUTIONS
Study Assignment and Background:
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7th Ed., by Howard C. Ansel et. al.
The purposes of this set of laboratory exercises are to:
study the methods of preparing some non-aqueous solutions, i.e., spirits, elixirs,
tinctures, collodions, and glycerites; and
to consider their physical and chemical properties.
-----------------------------------------------------------------------------------------------------------Although from their physical properties, various solvents may appear desirable for use in
pharmaceutical products, with few exceptions, organic solvents are irritating and toxic liquids. Nonpolar solvents used in liquid pharmaceutical dosage forms are: mineral oil; and vegetable oils e.g.,
corn, cottonseed, olive, and peanut oil. Van der Waals’ forces are the interaction forces in non-polar
solvents; consequently, the non-polar solvents do not dissolve ionic and polar substances. Polar
solvents (other than water) used for orally administered liquid dosage forms are: alcohol, glycerin and
propylene glycol. The use of isopropyl alcohol is limited to external preparations. Co-solvent - a
second solvent used in a mixture to increase the capacity of the first solvent to
dissolve one or more solutes, e.g. alcohol is frequently used as a co-solvent to water to increase the
solubility of poorly water-soluble drugs.
IV-A. Spirit
Prepare 60 mL of Peppermint Spirit, U.S.P. XXII
U.S.P. Formula
[1000 mL]
Reduced Formula
[60 mL]
........................
Peppermint Oil ...
100 mL
mL
....Peppermint,incoarsepowder
10 gm
gm
........................Alcohol,tomake
1000 mL
mL
Label:
Peppermint Spirit, U.S.P XXII
Procedure:
[From the U.S.P. for making 1000 mL]
“Macerate the peppermint leaves, freed as much as possible from the stems and coarsely
powdered for 1 hour in 500 mL (
mL*) of purified water, and then strongly express
Add the moist macerated leaves to 900 mL (
61
them.
mL*) of alcohol, and allow the mixture to stand for 6
hours (1-2 hours in this laboratory exercise) with frequent agitation. Filter, and to the filtrate, add the oil
and sufficient alcohol to make the product measure 1000 mL ( mL*). If the product is hazy at this point,
add about 1/2 teaspoonful of talc and filter until clear through a fluted filter.”
*Insert the reduced quantities here as only 60 mL is the quantity being prepared.
Package the spirit in a 2-oz. prescription bottle and label with the official name.
-----------------------------------------------------------------------------------------------------------------Peppermint Spirit, U.S.P.
Peppermint Spirit, U.S.P., is an alcoholic solution containing 10% peppermint oil and the
green colorant, chlorophyll, extracted with alcohol from coarsely ground peppermint.
Peppermint, N.F., consists of the dried leaf and flowering top of Mentha piperita. When fresh,
peppermint contains about 2% of peppermint oil. However, the oil is lost when the peppermint is
air-dried prior to packaging. The peppermint therefore is used in the preparation of the spirit not
for its oil content, but rather for the purpose of imparting a pleasant green color to the product. In
extracting the green chlorophyll from the peppermint, the drug first must be macerated with water
for about 1 hour to remove the brown water-soluble pigments. Then, the leaves are drained,
expressed of water, and macerated in alcohol with frequent agitation for a period of about 6
hours. If the peppermint were only macerated with alcohol, all coloring material, brown and green,
would be extracted, and the resulting spirit would not be as brilliantly colored as it is from green
chlorophyll alone. Chlorophyll resists extraction by water but is easily soluble in the alcohol. After
the peppermint is macerated in the alcohol, the mixture is filtered, and the peppermint oil
dissolved in the green-colored alcoholic filtrate. The spirit is then made to volume with additional
alcohol.
Peppermint spirit may be taken internally as a digestive aid in a dose of 1 mL. If it is mixed
with water, the mixture is milky but retains its medicinal value.
-----------------------------------------------------------------------------------------------------------------Study Questions on Spirits
In making Peppermint Spirit, what is the purpose of the initial extraction of the leaves with water?
(See above)
Does chlorophyll resist extraction with water? (Check one)
What is the purpose of the second extraction of the leaves with alcohol?
What is maceration?
What is expression?
62
The peppermint leaves are described as a “coarse powder”. What is the sieve size of a
vegetable powder described as “coarse”?
If a spirit is to be filtered during its manufacture, why should a water-wetted paper be
avoided?
What alternative to water-wetted paper is suggested?
------------------------------------------------------------------------------------------------------------IV-B. Elixir
Prepare 120 mL of Terpin Hydrate Elixir, U.S.P. XXII
U.S.P. Formula for 1000 mL
Reduced Formula for 120 mL
Terpin Hydrate
17 gm
gm
Sweet Orange Peel Tincture.
20 ml
mL
Benzaldehyde*
50 µL
µL =
=
drops of a
10% alcoholic spirit
Glycerin
400 mL
mL
Alcohol
430 mL
mL
Syrup
100 mL
mL
Purified Water, qs ad
1000 mL
mL
*Supplied as Benzaldehyde Spirit which is a 10% v/v solution of benzaldehyde in
alcohol in dropper bottles delivering 40 drops/mL
------------------------------------------------------------------------------------------------------------
63
mL
Procedure:
[From the U.S.P. for preparing 1000 mL of elixir.]
Dissolve the terpin hydrate in the alcohol.
Add successively the tincture, the benzaldehyde, the glycerin;,the syrup, and sufficient
purified water to make the product measure 1000 mL.
Mix, and filter, if necessary, until the product is clear.
Package the elixir in a 4-oz prescription bottle and label with the official name.
Terpin Hydrate Elixirs
There are three (3) terpin hydrate elixirs: Terpin Hydrate Elixir, U.S.P.; Terpin
Hydrate Elixir with Codeine, U.S.P. and Terpin Hydrate Elixir with Dextromethorphan
Hydrobromide, U.S.P. The latter two are solutions of the antitussive agents codeine and
dextromethorphan HBr in Terpin Hydrate Elixir, U.S.P. Codeine is a narcotic antitussive
agent, whereas dextromethorphan hydrobromide is a non-narcotic antitussive agent.
Each is effective in blocking the cough reflex. Terpin Hydrate Elixir with Codeine is
commonly referred to as “ETH&C”.
Terpin Hydrate Elixir, U.S.P. represents an elixir that contains, as the therapeutic
agent, material that has a low water solubility but high alcohol solubility. Therefore, the
elixir requires a rather high final alcoholic strength (39 to 44%) and is prepared with an
“order of mixing” of the components that assures the highest possible alcoholic content
throughout its preparation. This is accomplished by delaying to the end, the addition of
components having substantial proportions of water. Terpin hydrate elixir and its
companion elixirs are immiscible with water, as the alcohol-soluble components
separate.
Study Questions on Terpin Hydrate Elixir
Why are the syrup and water last in preparing Terpin Hydrate Elixir (see above).
How many official Terpin Hydrate elixirs are found in the U.S.P. (see above).
What product is commonly known as “ETH&C”?
What is the therapeutic indication of Terpin Hydrate?
64
What is the therapeutic indication of codeine and dextromethorphan in these elixirs?
Indicate the solubility of terpin hydrate in water?
Indicate the solubility of terpin hydrate in alcohol?
----------------------------------------------------------------------------------------------------------IV-C. Tincture
Thimerosal Tincture, U.S.P. XXII (Prepare 30 mL of this tincture)
U.S.P. Formula
[1000 mL]
Thimerosal
Reduced Formula
[30 mL]
1.0 gm
gm =
mL of
Stock Solution*
Alcohol
525.0 mL
mL
Acetone
100.0 mL
mL
Ethylenediamine
0.2 gm
gm
Monoethanolamine
1.0 gm
gm =
mL of a
single stock solution**
Purified Water
1000 mL
mL
-------------------------------------------------------------------------------------------------------
*The thimerosal needed will be available as a stock solution in water containing 1%
thimerosal. Calculate the mL of this stock solution needed to supply the required
quantity of thimerosal and enter the volume in the appropriate blank space above.
**The ethylenediamine and monoethanolamine needed will be provided as a single aqueous stock
solution of the following strength:
Ethylenediamine
0.1%
Monoethanolamine
0.5%
Calculate the mL of this stock solution needed to supply the required quantities of each
of these chemicals and enter the volume in the appropriate blank above.
Procedure:
To a 30 mL (or one fl. oz) conical graduate, add the calculated amount of
Thimerosal Stock solution followed by the calculated amount of the stock solution
containing ethylenediamine and monoethanolamine.
Then add the amount of alcohol and acetone calculated, followed by enough water to
bring the total volume to 30 mL.
65
Mix thoroughly and filter if necessary.
Package in a one ounce prescription bottle and label with the official name.
Include a strip label of the following type (See next page):
EXTERNAL
USE
Study Questions on Thimerosal Tincture
By what name does Eli Lilly and Company market Thimerosal Tincture?
What cautions concerning the manufacture and storage are listed in the U.S.P. for Thimerosal
Tincture?
What color is the commercially available Thimerosal Tincture and what will it do to a
patient’s integument. (Check Reference)
-------------------------------------------------------------------------------------------------------IV-D. Prepare the following prescription:
Amounts used
Rx
Salicylic Acid
10%
Glacial Acetic Acid 10%
Flexible Collodion, ad
gm
mL
30 mL
M. ft. sol.
Sig: Apply to wart b.i.d. p.r.n.
----------------------------------------------------------------------------------------------------Procedure:
66
Place the required amount of salicylic acid and glacial acetic acid in a 1 fl. oz
conical graduate.
Add about 2/3 of the required Flexible Collodion.
Mix until the acids are dissolved.
Qs to volume with the Flexible Collodion in the conical graduate.
Package in a 1-oz applicator bottle and label.
Use an EXTERNAL USE label also.
Study Questions On The Above Prescription
What are collodions? (Remington: The Science and Practice of Pharmacy, 19th ed., Volume II.)
What is the official medicated collodion? (Remington: The Science and Practice of Pharmacy, 19th
ed., Volume II.)
What ingredients are added to Collodion U.S.P., to prepare Flexible Collodion, U.S.P., and render the
product both flexible and waterproof?
What is the therapeutic indication for salicylic acid collodion?
Name two (2) commercially available products that are similar to salicylic acid collodion?
What advise will you, as a pharmacist, give to a patient using salicylic acid collodion to help
prevent irritation to the healthy skin surrounding the wart?
67
----------------------------------------------------------------------------------------------------------------IV-E. Glycerites
Glycerites
[From the 2nd edition]
“Glycerites are solutions or mixtures of medicinal or pharmaceutical substances in
glycerin. Generally, a minimum of 50% of glycerin is present in glycerites. Owing to the
high concentration of glycerin and the presence of large amounts of dissolved or
undissolved solids glycerites are generally quite viscous with some of them reaching a
jelly-like consistency.
Glycerin has a wide range of solvent power and is capable of dissolving a number of
substances that may be insoluble or unstable in other solvents. Because glycerin possesses
preservative capabilities, glycerites are considered to be stable preparations and are not usually
as prone to microbial contaminations as are aqueous preparations. Since glycerin is miscible with
both water and alcohol, glycerites generally may be diluted with these solvents or with aqueous or
alcoholic solutions as required.
Glycerites are not nearly as popular today as they once were probably due to increased
methods of stabilizing and preserving aqueous solutions, an increased capability to create and
utilize new salt forms of drugs having specifically desired chemical and physical features, the
application of newly developed solubilizing agents, and also the expense of glycerin as a sole
solvent. However, it should be remembered that glycerin is still today a valuable co -solvent in
many liquid pharmaceutical preparations, adding permanency to the preparation in which it is
used.”
------------------------------------------------------------------------------------------------------------------
Prepare the following prescription:
Rx
Phenol
5% =
grains of phenol
Glycerin, qs ad
M. ft. solution
fi
Sig: Instill 5 gtts q 2 h in affected ear(s).
---------------------------------------------------------------------------------------------------------------Procedure:
Weigh out the required amount of phenol.
Place it in a glass mortar.
Add about 20 mL of glycerin to the mortar and triturate until all the phenol is
dissolved.
Transfer the solution to a 1-oz. dropper bottle and label.
Add a strip label of the following type:
NOT TO BE TAKEN
BY MOUTH
68
Study Questions on the Above Prescription
What two (2) forms of phenol are official in the U.S.P.?
How much water is present in Liquified Phenol?
What is Carbolic Acid?
What is the therapeutic indication of this formulation?
Define, or otherwise explain, the term trituration? (Remington: The Science and
Practice of Pharmacy, 19th ed., p. 1612.)
69
Product Evaluation
IV-A. Peppermint Spirit
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Off color
Cloudy solution
Incorrect bottle
Other
Points
Points
total points for product
*Results in zero points for the entire product.
70
Product Evaluation
IV-B. Terpin Hydrate Elixir
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Cloudy solution
Precipitate
Incorrect bottle
Other
Points
Points
total points for product
*Results in zero points for the entire product.
71
Product Evaluation
IV-C. Thimerosal Tincture
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Cloudy solution
Precipitate
Incorrect bottle
Other
Points
Points
total points for product
*Results in zero points for the entire product.
72
Product Evaluation
IV-D. Collodion
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Cloudy solution
Precipitate
Incorrect bottle
Other
Points
Points
total points for product
*Results in zero points for the entire product.
73
Product Evaluation
IV-E. Glycerites
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Cloudy solution
Precipitate
Incorrect bottle
Other
Points
Points
total points for product
*Results in zero points for the entire product.
74
Laboratory #4 - Non-Aqueous Solutions
Grade Sheet
Product Points
IV-A
IV-B
IV-C
IV-D
IV-E
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
Signature of Instructor:
75
Laboratory No. 5
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (8771-336-01)
POLYPHASIC SYSTEMS: SOLIDS DISPERSED IN LIQUIDS
Study Assignment and Background:
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7th Ed., by Howard C. Ansel
The purposes of this set of laboratory exercises are to:
become familiar with the properties and methods of preparing several disperse
systems in which solids are dispersed in liquids; and
become familiar with the use of suspending agents as adjuncts to preparing
dispersions of solids in liquids.
----------------------------------------------------------------------------------------------------------------V-A. Ephedrine Sulfate Jelly, 1%
Ephedrine Sulfate Jelly was official in N.F. XII using tragacanth as the hydrophilic organic jelling
agent. However, because of the variability in the behavior of tragacanth, results were not always
predictable. Consequently, an unofficial formula will be used and is given below. This formula uses
methylcellulose, 4000 cps, in a 5% concentration as the jelling agent. Methyl-cellulose is a non-ionic
synthetic derivative of cellulose which can be made to have variable solubility and viscosity-inducing
properties depending upon the number of methoxy groups introduced per glucose moiety of the cellulose
molecule. The different types of methylcellulose are often distinguished by numbers such as
methylcellulose 400, methylcellulose 4000, etc. The numbers stand for cps values where cps is
centipoise, a unit of viscosity and, in particular, means the viscosity of a 2% solution of the particular
methylcellulose at 20° C, where the viscosity is measured in cps.
Prepare 30 grams of Ephedrine Sulfate Jelly using the following formula:
Ephedrine sulfate................
0.30 gm
Methylcellulose 4000............
1.50 gm
Purified water....................
28.20 gm
Procedure:
Weigh the ephedrine sulfate and methylcellulose and set aside on labeled papers.
In a 100-150 mL beaker, heat 28.2 gm (or mL) of water to just boiling, then add the
ephedrine sulfate and methylcellulose to the hot water and stir until the methylcellulose is well
dispersed.
Stir the solution very gently to dissolve the ephedrine sulfate and disperse
the methylcellulose.
Place the beaker in a crushed ice bath (use a 400-600 mL beaker with some ice and
water in it).
76
Continue very gentle stirring to keep the methylcellulose in suspension as the mixture
cools and thickens.*
[Note: Too vigorous stirring will incorporate excessive air bubbles into the thickening
dispersion as it gels and the air bubbles cannot be removed later.]
The thickened mixture will begin to “clear up” as the methylcellulose dissolves. Stop
stirring at this point and allow the jelly to remain for 60 minutes to complete dissolution
of the methylcellulose and jelling.
Package the jelly in an ointment tube using the technique demonstrated in class.
Label the tube: Ephedrine Sulfate Jelly, 1%.
*Note: Methylcellulose is more readily wetted and dispersed by hot water rather than
cold water but is more soluble in cold water than in hot water.
Study Questions
What is the therapeutic use of Ephedrine Sulfate Jelly? (Reference: “Handbook of Nonprescription
Drugs”, Chapter on “Cold and Allergy Products”.)
Which “Modified Cellulose”, methylcellulose or sodium carboxymethylcellulose, exhibits the fewest
“incompatibilities” in pharmaceutical formulations.
Explain your answer to Question 2.
77
What therapeutic use is made of methylcellulose when it is taken orally?
Describe the solubility of ephedrine sulfate in the following:
Water:
Alcohol:
How much Ephedrine Sulfate would be needed to prepare 120 gm of a 2% jelly? SHOW ALL
WORK. Place the answer in the answer box.
Answer
-----------------------------------------------------------------------------------------------------------V-B. White Lotion U.S.P. XXII
Prepare the following formulation:
Zinc Sulfate
4.8 gm
Sulfurated Potash
4.8 gm
Purified water, qs ad
120.0 mL
Procedure:
Dissolve the zinc sulfate and sulfurated potash separately, each in 55 mL of purified water.
Filter the zinc solution, if necessary, into a 4 fl. oz. graduate.
Filter the sulfurated potash solution into the graduate containing the zinc sulfate solution, stirring the
zinc sulfate solution continuously so that a fine-grained precipitate forms as the sulfurated potash solution
flows into the graduate
When the filtration is completed, qs the graduate to 120 mL (4 fl. oz.) with purified water, mix, and
transfer to a 4 fl. oz. bottle
Label the bottle: White Lotion, U.S.P. XXII and include a “SHAKE WELL” and “EXTERNAL USE”
label.
------------------------------------------------------------------------------------------------------------
Note: The order of mixing in “White Lotion” is important and many pharmacists remember this order
by using the statement, “the stink to the zinc”, which reflects the fact that the malodorous
78
sulfurated potash solution is added to the zinc sulfate rather than the reverse. If one
reverses the order of mixing, then precipitate is coarser due to the changed “chemistry”
of the precipitate formation. That is, sulfurated potash solutions are alkaline, while zinc
sulfate solutions are acidic.
(a) By incremental addition of the alkaline sulfurated potash solution to the total volume of acidic zinc
sulfate, the precipitate forms under acidic conditions and assures that the following representative
reaction occurs:
+
[H due to acidic ZnSO4]
ZnSO4 + K2Sx ——— ZnS + 2S + K2SO4 The desired
precipitates.
If the reverse order of mixing is followed, incremental amounts of acidic zinc sulfate
solution are added to the total volume of alkaline sulfurated potash solution where
the following representative reaction occurs:
-
[OH due to alkaline K2S]
ZnSO4 + K2Sx
———
ZnS + 2S + Zn(OH)2 + K2SO4
The desired precipitates are formed together with Zn(OH)2, an undesired coarse
precipitate.
Study Questions
Why must this lotion be “freshly prepared”?
What is the therapeutic use of White Lotion?
The description of Sulfurated Potash in “Remington’s Pharmaceutical Sciences” reads in part
as follows:
“...irregular pieces, liver-brown when freshly prepared, changing to a greenish yellow...”
What synonym for Sulfurated Potash reflects this description and appearance?
Why should White Lotion be dispensed in “tight” containers?
79
5. If the formula for Rx V-B “White Lotion U.S.P. XXII” is enlarged to 500 mL, how much zinc sulfate
would be needed to make this preparation? SHOW ALL WORK. Place the answer in the answer box.
Answer
-----------------------------------------------------------------------------------------------------------------V-C.
The following prescription is a shake lotion designed by a dermatologist and appearing on
prescription for his/her patients. It contains both the hydrophilic powder, zinc oxide, and the hydrophobic
powder, precipitated sulfur. In order to prepare a satisfactory lotion with well-dispersed particles of sulfur,
the wetting agent, dioctyl sodium sulfosuccinate (currently called Docusate Sodium, U.S.P.) will be
included in the formula, secumdem artem. The source of this wetting agent will be Colace Capsules,
100 mg, a trade name for a “stool softener” type laxative and is available over-the-counter.
Rx
Precipitated Sulfur
10|0
Zinc Oxide
3|0
Rose Water, qs ad
60|0
M. et ft. lotion s.a.
Sig: apply to face daily h.s.
--------------------------------------------------------------------------------------------------------------Procedure:
1. Weigh out the sulfur and zinc oxide and place in a glass mortar.
80
Triturate these powders lightly to mix them and eliminate lumps in the sulfur.
Add about 25 mL of Rose Water to the mortar and mix with the powders by
trituration.
[Note: After this initial addition of aqueous solution, observe the behavior of the
powders.]
a. Do they seem to disperse well in the water? (Check one):
Yes
No
b. If “no”, which of the two powders appears to be the source of the problem?
(Check one):
Precipitated Sulfur
Zinc Oxide
With a razor, cut the tip off a Colace Capsule, 100 mg, and then squeeze the liquid
contents out of the capsule shell into the mortar and mix into the mortar and mix into
the suspension by trituration.
[Note:
a. After this addition of Docusate Sodium, does the “dispersability” of the
powders into the water seem to change? (Check one):
b. If “yes”, to what degree? (Check one):
Better
Worse
Transfer the suspension from the mortar at this point into a 2-oz. bottle and rinse
residual powders from the mortar with Rose Water until the bottle is brought to a final
volume of 2-oz. (or 60 mL).
Label the bottle with the translated “sig” plus a “SHAKE WELL” and “EXTERNAL
USE” label.
Study Questions
If a surfactant is an effective “wetting agent”, in what range should its HLB occur?
Why is Precipitated Sulfur preferred to Sublimed Sulfur for use in dermatologicals?
What purpose does the Rose Water serve in this formulation?
81
What does “secundum artem” mean?
The formula in Rx V-C have the amounts of each ingredient with a line running through the amounts.
a. What does the line stand for?
b. What system of measurement is this prescription written in?
-------------------------------------------------------------------------------------------------------------------V.D
Prepare 120 mL of Kaolin Mixture with Pectin, N.F. XIII.
The formula in the N.F. XIII is:
Reduced Quantities
Kaolin
200 gm
gm
Pectin
10 gm
gm
Tragacanth, powdered
5 gm
gm
Benzoic Acid
2 gm
gm
Sodium Saccharin
1 gm
gm
Glycerin
Peppermint Oil*
Purified Water, qs ad
20 mL
mL
0.75 mL
1000 mL
mL =
120 mL
*Peppermint Oil is available in dropper bottles, 45 drops/mL.
Procedure:
[Note: place the reduced quantities in the blank spaces, as the procedure is for 1000 mL.]
82
drops
1. Mix the kaolin with 500 mL (
mL) of purified water.
Triturate the pectin, tragacanth, and sodium saccharin with the glycerin.
Add to the triturated material, with constant stirring, the benzoic acid dissolved in 300
mL (
mL) of boiling purified water.
Allow the mixture to stand until it cools to room temperature and all the pectin is
dissolved.
Add the peppermint oil and the kaolin-water mixture, and mix thoroughly.
6. Qs to 1000 mL (
mL) with purified water.
Package in a 4 fl. oz. bottle, label with the product name and use a “SHAKE WELL”
label.
Study Questions
What is the name of a commercial product manufactured by three (3) pharmaceutical companies
which are similar to Kaolin Mixture with Pectin N.F. XIII? (Reference: “Handbook of
Nonprescription Drugs”, Chapter on “Antidiarrheal and Other Gastrointestinal Products”.)
Complete the table:
Product
Dosage Form
Manufacturer
What is the purpose of benzoic acid in the formula?
What is the purpose of kaolin in the formula?
What are the mechanisms of action of Kaolin Mixture with Pectin?
83
What is kaolin?
What is pectin?
If the sig of Rx V-D is “15 mL after each loose stool”:
a. How many mg of kaolin are in each dose? SHOW ALL WORK. Place the answer in the
answer box.
Answer
How many mg of Pectin are in each dose? SHOW ALL WORK. Place the answer in the
answer box.
Answer
84
c. How many doses can be obtained from a 120 mL bottle. SHOW ALL WORK. Place the
answer in the answer box.
Answer
d. What household measure would you instruct the patient to use to take the desired
dose?
Product Evaluation
V-A. Ephedrine Sulfate Jelly
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
85
Product
Incorrect volume
Excessive air bubbles
Cloudy jelly
Improper consistency
Packaged in an incorrect container
Jelly leaking from tube
Other
Points
Points
total points for product
*Results in zero points for the entire product.
86
Product Evaluation
V-B. White Lotion
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Incorrect bottle
Coarse precipitate
Other
Points
Points
total points for product
*Results in zero points for the entire product.
87
Product Evaluation
V-C. Shake Lotion
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Incorrect bottle
Other
Points
Points
total points for product
*Results in zero points for the entire product.
88
Product Evaluation
V-D. Kaolin Mixture
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Incorrect bottle
Undissolved material
Other
Points
Points
total points for product
*Results in zero points for the entire product.
89
Laboratory #5 - Solids Dispersed in Liquids
Grade Sheet
Product Points
V-A
V-B
V-C
V-D
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
Signature of Instructor:
90
Laboratory No. 6
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (8771-336-01)
POLYPHASIC SYSTEMS: EMULSIONS
Study Assignment and Background:
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7th Ed., Howard C. Ansel, et.al.
The purposes of this set of laboratory exercises are to:
become familiar with the use of emulsifiers of the gum, protein, non-ionic
surfactant, and anionic soap types in making emulsions; and
become familiar with extemporaneous processes for preparing emulsions.
----------------------------------------------------------------------------------------------------------------VI-A. Cod Liver Oil Emulsion
Certain proteins such as gelatin, egg yolk, and casein can be used as the emulsifier in preparing
emulsions. Gelatin will be used in this cod liver oil emulsion. Gelatin, U.S.P., is described as follows:
Gelatin is a product obtained by the partial hydrolysis of collagen derived from the skin, white
connective tissue, and bones of animals. Gelatin derived from an acid-treated precursor is known
as Type A, and Gelatin derived from an alkali-treated precursor is known as Type B.
Gelatin is a zwitterionic substance and Type A gelatin carries a net positive charge in aqueous
solution and must be used at acidic pH to maintain the positive charge. Tartaric acid is generally added to
solutions of Type A gelatin to aid in maintaining the acidity. Type B gelatin carries a net negative charge
in aqueous solution and must be used at alkaline pH to maintain its negative charge. Sodium bicarbonate
is generally added to solutions of Type B gelatin to maintain the alkalinity.
Gelatin emulsions are usually too thin to retard creaming well so that a thickening agent (sometimes
called an “Auxiliary emulsifier”) is added to increase the viscosity of the external phase. In the emulsion
made by the following formula, sodium carboxymethylcellulose is the auxiliary emulsifier.
91
Use the following formula and procedure for the Cod Liver Oil Emulsion:
Cod Liver Oil............................................................
60.0 mL
Gelatin, Type B*.......................................................
0.6 gm
Sodium Bicarbonate................................................
0.3 gm
Alcohol.....................................................................
8.0 mL
Sweet Orange Peel Tincture.....................................
1.0 mL
Sodium Carboxymethylcellulose Solution, 1%.......
25.0 mL
Yellow Food Dye........................................................
2 drops
Purified Water, qs ad.................................................
120.0 mL
*Available under the tradename, Pharmagel B
--------------------------------------------------------------------------------------------------Procedure:
Calibrate a 250 mL beaker to the 120 mL mark, then place 25 mL of purified water in
the beaker and heat to about 70° C. Remove the beaker from the heat and add the
gelatin and stir until dissolved.
To the gelatin solution, add and dissolve the sodium bicarbonate, then add 25 mL of
1% carboxymethylcellulose solution and mix thoroughly.
To the gelatin solution, add the alcohol about 1 mL at a time with thorough mixing
after each addition.
Add the Sweet Orange Peel Tincture and mix.
Add the Yellow Food Dye and mix.
Add the Cod Liver Oil to the gelatin solution and stir vigorously in the beaker until a
coarse emulsion forms.
Bring the emulsion to the 120 mL volume with purified water and mix.
Pass the emulsion through the hand homogenizer, collecting it in the same 250 mL
beaker from which you emptied it into the homogenizer.*
Transfer the emulsion to a 4 fl. oz. bottle and label:
COD LIVER OIL EMULSION
10. Add a “SHAKE WELL” label to the bottle.
*Note: Satisfactory emulsions cannot be formed in a mortar with gelatin as the
emulsifier or by simple shaking; however, by passing a coarse gelatin emulsion
through a homogenizer, a fine-grained emulsion can be prepared.
92
Study Questions
1. Is this emulsion a w/o or an o/w emulsion? (Check one)
[Remember the Bancroft Rule: The phase in which the emulsifier has the greater solubility
tends to be the external phase.]
w/o
o/w
Is sodium
carboxymethylcellulose:
(Check
one) anionic
cationic
non-ionic
Knowing that the alcohol added is 95% v/v, and that it does not enter the oil phase, calculate the final
concentration of alcohol in the aqueous phase of the emulsion, disregarding the alcohol in the Sweet
Orange Peel Tincture.
Is the concentration of alcohol calculated in Question 3 (above) sufficient to be an antimicrobial
preservative for the aqueous phase of the emulsion? (Check one):
Yes
No
Cod liver oil is a source of what vitamins? (Remington: The Science and Practice of Pharmacy, 19th
ed.)
How much of each vitamin is contained in a 5 mL dose of Cod liver oil?
From the “Cod Liver Oil Emulsion” formula in R x VI-A, how much Cod liver oil is in a 5 mL
dose. SHOW ALL WORK. Place the answer in the answer box.
Answer
93
8. How many g of each vitamin would a 5 mL dose of Cod Liver Oil Emulsion provide?
SHOW
ALL WORK. Show the answer in the answer box.
Answer
------------------------------------------------------------------------------------------------------------------VI-B. Castor Oil Emulsion
In this preparation, the very common gum emulsifier, acacia, will be used with a “fixed oil” to make an
emulsion using a mortar and pestle and employing the “dry gum method”. The “dry gum” method
requires an oil:water:gum ratio of 4:2:1 for fixed vegetable oils, i.e., 4 parts by volume of oil to 2 parts by
volume of water to one part by weight of acacia.
Use the following formula and procedure:
Castor Oil............................
50 mL
Acacia, finely powdered............
12.5 gm
Peppermint Oil......................
3 drops
Green Food Color..................
2 drops
Peppermint Water, qs ad..........
90 mL
In a dry conical graduate, measure the castor oil and place it in a dry porcelain mortar.
Add the peppermint oil to the mortar and mix well.
To the oil in the mortar, add all of the powdered acacia and triturate until it is
uniformly distributed in the oil.
Add 25 mL of Peppermint Water all at once to the mortar and then immediately
triturate briskly until the primary emulsion (or “emulsion nucleus”) is well formed.
94
The emulsion becomes creamy white and “snaps and pops”; about 3 minutes of
trituration is generally needed.
(Note: It is not necessary to exert heavy pressure as in grinding powders in this step.)
Add the Green Food Color and mix.
Triturate about 5 mL of Peppermint Water into the emulsion to make it thinner and
more pourable.
Pour the emulsion into a 3-oz. bottle and rinse the mortar with small portions of
Peppermint Water, transferring these rinsings to the bottle until 3 fl. oz. is obtained.
Label:“CASTOR OIL EMULSION” and add a “SHAKE WELL” label.
Study Questions
How would the procedure change in making the primary emulsion if the “English”, or “wet gum
method” was used?
If this emulsion contained 50 mL of Liquid Petrolatum (or “Mineral Oil”) instead of Castor Oil, how
much oil, water and acacia would be used? (“Pharmaceutical Dosage Forms and Drug Deliver Systems”,
h
7 ed.)
What is the therapeutic use of this emulsion?
What is its mechanism of action?
Define, or otherwise explain the term rancidity?
95
How does rancidity occur?
th
What is a “fixed oil”? (Remington: The Science and Practice of Pharmacy, 19 ed.)
What are the two source of most fixed oils? (Remington: The Science and Practice of
th
Pharmacy, 19 ed.)
th
List five (5) official fixed oils. (Remington: The Science and Practice of Pharmacy, 19 ed.)
Official Fixed Oils
1.
2.
3.
4.
5.
10. What type of laxative is Castor Oil Emulsion?
--------------------------------------------------------------------------------------------------------------VI-C.
Mineral Oil Emulsion
Surfactant type agents are useful emulsifiers and are available as anionic, cationic, and non-ionic
surfactants. In this prescription, two non-ionic surfactants will be blended to produce an o/w emulsion of
mineral oil using the following formula and procedure:
Mineral Oil..............................
48.00
gm
Sodium benzoate.......................
0.24
gm
Anise oil................................
5
drops
Emulsifier*.............................
8.4
gm
Tween 40 [HLB = 15.6] =
Span 40 [HLB = 6.7] =
96
gm
gm
Purified Water, qs ad..................
120.0 mL
*Note: A total emulsifier quantity of 8.4 gm will be used. Calculate the quantity of Tween
40 and Span 40 needed knowing that the “required HLB” of mineral oil for making a o/w
emulsion is 12.0. Place the results of your calculations in the blank spaces at the right
above.
Calibrate a 250 mL beaker to the 120 mL mark, weigh it and then weigh into it
the mineral oil needed.
Add the anise oil and the Span 40.
Warm the oil to about 60-65° C until the Span 40 dissolves.
Dissolve the sodium benzoate and Tween 40 in 50 mL of purified water warmed to 60-65°
C.
Add the warm water solution to the warm oil solution and stir vigorously in the beaker
until an emulsion forms.
Bring the volume to 120 mL with water.
Transfer to a 4 fl. oz. bottle
Shake the bottle periodically while the emulsion cools.
Label: “MINERAL OIL EMULSION”
Use an auxiliary “SHAKE WELL” label.
Study Questions
If the same 120 mL of emulsion above were formulated into a w/o emulsion using Tween 60 (HLB =
9) and Span 60 (HLB = 4.7) as the emulsifiers, and you used 8.4 gm total emulsifier, how many grams
of each of the Tween 60 and Span 60 would you use?
[Note: The “required HLB” for mineral oil to form a w/o emulsion is 5.0]
Tween 60:
gm
Calculations:
Span 60:
Calculations:
97
gm
What is the emulsifying agent in Mineral Oil Emulsion, U.S.P. XXII?
Guided by the Bancroft Rule, would you expect the emulsion of Mineral Oil U.S.P. XXII to be an o/w or
a w/o system? (Check one):
o/w
w/o
Which mineral oil, light or heavy, is used in making Mineral Oil Emulsion? (Check one):
Light Mineral Oil
Heavy Mineral Oil
Explain your choice to Question 4 (above).
---------------------------------------------------------------------------------------------------------VI-D. Calamine Liniment
Soaps are anionic surfactants and can be used as emulsifiers. If the soap is water soluble, e.g., fatty
acid salts of sodium, potassium, ammonium, and amines, the emulsion tends to be o/w. If the soap is
water insoluble, but oil soluble, e.g., fatty acid salts of calcium, magnesium, aluminum, etc., then the
emulsion tends to be w/o. In this prescription, calcium hydroxide solution is allowed to react in situ with
cottonseed oil which contains some free oleic acid which forms calcium oleate. The calcium oleate then
promotes the formation of a w/o emulsion.
[Note: In cottonseed oil, most of the oleic acid is present in ester linkages to the glycerin to form
“triglycerides”, but there is always some of the ester which is hydrolyzed to yield free oleic acid and
glycerin. However, if the amount of free acid is inadequate to produce sufficient calcium oleate, then the
emulsification process may not be successful. In such cases, the problem can be resolved by adding a
few drops of oleic acid to the oil.]
Use the following formula and procedure:
Calamine
Zinc Oxide
Cottonseed oil
98
aa
4.0 gm
Calcium Hydroxide Solution
aa
50.0 mL
Procedure:
Place the zinc oxide and calamine in a mortar and add the oil incrementally with
trituration until a smooth suspension is obtained.
Gradually add the Calcium Hydroxide Solution with trituration until the emulsion is
formed.
Transfer the emulsion to a 4 fi. oz. bottle and label: “CALAMINE LINIMENT”.
Use both a “SHAKE WELL” and “EXTERNAL USE ONLY” label.
[Note: The oil:lime water ratio must be about 50:50 in vegetable oil:lime water for the
emulsion to be successful. If powders are not present in the formula, a successful
emulsion of the oil and lime water can be prepared by merely vigorously shaking equal
volumes of the oil and lime water in a bottle.]
Study Questions
Cottonseed oil has a specific gravity of about 0.9. Would you expect the dispersed droplets of the
emulsion prepared in Calamine Liniment above to settle to the bottom or rise to the top? (Check one):
Settle to the bottom
Rise to the top
Explain your answer to Question 1 (above).
Knowing that the specific gravity of cottonseed oil is 0.9, what is the volume of 1500 gm of
cottonseed oil? SHOW ALL WORK. Show the answer in the answer box.
Answer
99
What is the chief constituent of calamine?
What is the source of the color in calamine?
Provide two (2) names and manufacturers of over-the-counter products similar to Calamine Liniment?
Name of Preparation
100
Manufacturer
Product Evaluation
VI-A. Cod Liver Oil Emulsion
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Incorrect color
Incorrect bottle
Incorrect consistency
Broken emulsion
Other
Points
Points
total points for product
*Results in zero points for the entire product.
101
Product Evaluation
VI-B. Castor Oil Emulsion
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Incorrect color
Incorrect bottle
Incorrect consistency
Broken emulsion
Other
Points
Points
total points for product
*Results in zero points for the entire product.
102
Product Evaluation
VI-C. Shake Lotion
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Incorrect bottle
Incorrect consistency
Broken emulsion
Other
Points
Points
total points for product
*Results in zero points for the entire product.
103
Product Evaluation
VI-D. Calamine Liniment
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect volume
Incorrect bottle
Incorrect consistency
Broken emulsion
Other
Points
Points
total points for product
*Results in zero points for the entire product.
104
Laboratory #6 - Emulsions
Grade Sheet
Product Points
VI-A
VI-B
VI-C
VI-D
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
Signature of Instructor:
105
Laboratory No. 7
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (87771-336-01)
SEMISOLID DOSAGE FORMS: OINTMENT BASES
Study Assignment and Background:
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7 th Ed., by Howard C. Ansel
The purpose of this set of laboratory exercises is to learn and understand the preparation and
properties of some ointment bases.
-------------------------------------------------------------------------------------------------------------------Definitions:
Ointment base: A semisolid preparation that in itself has no physiologic activity. It may function as a
protective or emollient for the skin, but is used primarily as a vehicle for the topical application of
more active medicinal substances.
[Note: Four (4) representative ointment bases will be prepared in this
laboratory experiment and
then
three (3) bases will be used to make three (3) medicated ointments in Laboratory Number 8.
Ointment: A semisolid, medicated preparation intended for external application,and of such
consistency that it may be readily applied to the skin by rubbing (“inunction”). It should be of such
composition that it softens, but not necessarily melts, when applied to the skin.
Classification of Ointment Bases:
Pharmaceutically, ointment bases are classified by the U.S.P. XXI as follows:
1.
Hydrocarbon bases (also called “oleaginous” bases)
2.
Absorption bases
3.
Water-removable bases
4.
Water-soluble bases
Each of these will be discussed further below.
Hydrocarbon bases - Bases in this category have also been called “oleaginous” to
reflect
the fact that, historically, not only have hydrocarbons been used in such bases, but that the fatty acid
esters of glycerin such as animal fats and vegetable oils have been used in preparing such bases. The
hydrocarbons are obtained from petroleum sources and are available in products of varying consistency
from liquids, e.g., Liquid Petrolatum, to semisolid, e.g., Petrolatum, to solid, e.g., Paraffin. They may
be blended in different proportions to yield products of any consistency. The glycerides of fatty acids are
less used today than formerly, because they are more prone to rancidity, the susceptibility of such
increasing with the degree of unsaturation in the fatty acid moiety of the oil.
From the viewpoint of the patient, oleaginous bases have the disadvantage of being
greasy and
difficult to remove from the skin; from the viewpoint of the pharmacist, they have the disadvantage of
106
being unable to absorb aqueous liquids. Therapeutically, oleaginous ointments hinder the loss of heat
from inflamed areas and prevent drainage from congested, oozing lesions. Absorption bases - The
U.S.P. divides these bases into two groups The first group are anhydrous themselves and may absorb appreciable amounts of
aqueous liquids because they contain an emulsifying agent which yields a water-in oil
emulsion. Examples of such absorption bases are Hydrophilic Petrolatum, U.S.P.,
and Anhydrous Lanolin, U.S.P. Probably the most widely used product
of this nature, however, is the commercial product, Aquaphor (Beiersdorf, Inc.).
The second group consists of water-in-oil emulsions that permit the incorporation
of additional quantities of aqueous solution. Examples are Cold Cream, U.S.P.,
and Lanolin, U.S.P. Some medicaments are absorbed somewhat better from these
bases than from the hydrocarbon bases.
Absorption bases are also useful as emollients.
Water-removable bases - Such bases are oil-in-water emulsions and are frequently called “creams”.
They are also described as “water-washable” since they may be readily washed from the skin or clothing
with water, an attribute that makes them more acceptable for cosmetic reasons. Some medicaments may
be more effective in these bases than in hydrocarbon bases. Other advantages of the water-removable
bases are that they may be diluted with water and that they favor the absorption of serous discharges in
dermatological conditions.
Water-soluble bases - This group of so-called “greaseless ointment bases” is composed of watersoluble constituents. Polyethylene Glycol Ointment, U.S.P., is the only official preparation in this group.
Bases of this type offer many of the advantages of the water-removable bases and, in addition, contain
no water-insoluble substances such as petrolatum, anhydrous lanolin, or waxes. Such bases may
absorb a very limited amount of aqueous solutions without becoming too soft or liquid. The U.S.P.
suggests the inclusion of stearyl alcohol where water or a water solution is to be incorporated in order to
minimize the resultant softening effect. The water-soluble bases may, in some instances, be irritating to
inflamed tissues.
Choice of Base The U.S.P. XXI states the following:
“The choice of an ointment base depends upon many factors, such as action desired,
the nature of the medicament to be incorporated and its bioavailability and stability, and
the requisite shelf-life of the finished product. In some cases, it is necessary to use a
base that is less than ideal in order to achieve the stability required. Drugs that
hydrolyze rapidly, for example, are more stable in hydrocarbon bases than in bases
containing water, even though they may be more effective in the latter.”
------------------------------------------------------------------------------------------------------------
107
VII-A.
Prepare 30 grams of White Ointment, U.S.P. XXI
U.S.P. Formula
Reduced Quantities
White Wax.......................
50 gm
gm
White Petrolatum............
950 gm
gm
To make...........................
1000 gm
30
gm
Melt the White Wax in a beaker on a water bath.
Add the White Petrolatum.
Warm until liquefied, then discontinue the heating.
Stir the mixture until it begins to congeal.
Package in a 1-oz. ointment jar and label with the official name.
Also include an “EXTERNAL USE” label.
Discussion:
This base represents a “hydrocarbon” type base and is the specified base in Sulfur
Ointment U.S.P., and Zinc Oxide Ointment, U.S.P. There is also an official Yellow
Ointment U.S.P. XX, which has an exactly analogous formula to that above except that
it contains 5% Yellow Wax and 95% Yellow Petrolatum.
Study Questions
What is an ointment base?
What is an ointment?
What is a synonym for:
White Petrolatum?
White Wax?
What is the name of a commercial product (made by Chesebrough-Pond’s) consisting of White
Petrolatum?
108
How does Petrolatum, U.S.P. differ from White Petrolatum, U.S.P.?
How does Paraffin, U.S.P. differ from Petrolatum, U.S.P.?
How does Wax (Yellow or White) differ as to source and chemical constituents from
Paraffin, U.S.P.?
PRODUCT
SOURCE
WAX, U.S.P. (Yellow or White)
PARAFFIN, U.S.P
Name two (2) disadvantages of hydrocarbon ointment bases?
a.
b.
109
CHEMICAL CONSTITUENTS
------------------------------------------------------------------------------------------------------------VII-B
Prepare 30 grams of Cold Cream, U.S.P. XXI
U.S.P. Formula
Reduced Quantities
Cetyl Esters Wax.............
125 gm
gm
White Wax....................
120 gm
gm
Mineral Oil....................
560 gm
gm
................SodiumBorate
5 gm
gm
.................PurifiedWater
190 mL
mL
To make........................
1000 gm
30
gm
Procedure:
Reduce the Cetyl Esters Wax and the White Wax to small pieces.
Melt these substances on a steam bath.
Add the mineral oil.
Continue heating until the temperature of the mixture reaches 70° C.
Dissolve the sodium borate in the purified water, warmed to 70° C.
Gradually add the warm sodium borate solution to the melted mixture on the
water bath, stirring rapidly and continuously until it has congealed.
Package in a 1-oz. ointment jar and label with the official name.
Add the auxiliary label: “EXTERNAL USE”.
Discussion:
This base represents, according to the current U.S.P. classification, an absorption base of the
second type, i.e., a water-in-oil emulsion with the capacity to absorb additional amounts of aqueous
solutions. It probably should be noted that many classification systems would not consider this an
absorption base, but would rather include water-in-oil emulsion and oil-in-water emulsions together under
the classification of Emulsion Bases.
Study Questions
What is the emulsifier in this water-in-oil emulsion?
What natural source material has been replaced in this formula by “Cetyl Esters Wax”?
What is the synonym for Cetyl Esters Wax?
110
What is the chemical nature of Cetyl Esters Wax?
How does Cold Cream, U.S.P., differ from Rose Water Ointment, U.S.P. in formula?
What advantage does Cold Cream possess over Rose Water Ointment as far as stability is
concerned?
Provide two (2) examples of Official (U.S.P.) anhydrous absorption bases
a.
b.
What is the most widely used commercial product in the “absorption base” classification?
9.
Lanolin U.S.P. contains not less than
10. Anhydrous Lanolin U.S.P. contains not more than
% and not more than
% of water.
% of water.
Which base, Lanolin U.S.P. or Anhydrous Lanolin U.S.P. would absorb the most water. (Check one):
Lanolin U.S.P.
Anhydrous Lanolin U.S.P.
Explain your answer.
111
VII-C.
Prepare 30 grams of Hydrophilic Ointment, U.S.P. XXI
U.S.P. Formula
Reduced Quantities
Methylparaben*.................
0.25 gm
gm
Propylparaben*.................
0.15 gm
gm
mL
of Stock solution
Sodium Lauryl Sulfate........
10.0 gm
gm
Propylene Glycol.............
120.0 gm
gm
Stearyl Alcohol...............
250.0 gm
gm
White Petrolatum.............
250.0 gm
gm
Purified Water................
370.0 gm
gm
To make.......................
1000.0 gm
30
gm
*The “parabens” will be supplied in an alcoholic stock solution containing 15 mg/mL of
Methylparaben and 9 mg/mL of Propylparaben.
Procedure:
Melt the stearyl alcohol and the white petrolatum on a steam bath.
Warm to about 75° C.
Add the other ingredients, previously dissolved in the purified water also warmed to
75° C.
Stir the mixture until it congeals.
Package in a 1-oz. ointment jar and label with the official name.
Also add an auxiliary label: “EXTERNAL USE”.
Discussion:
This base represents a “water removable” base or a “washable” base. It is an oil-inwater emulsion system and can be diluted with additional amounts of water. Some
classification systems would include both this base and Cold cream under a category of
Emulsion Bases.
Study Questions
1. What is the HLB of sodium lauryl sulfate?
2. Would this HLB for sodium lauryl sulfate imply greater water or oil solubility? (Check
one):
Greater Water solubility
Greater Oil solubility
Would the Bancroft Rule imply a w/o or an o/w emulsion system from using an emulsifier with such
solubility? (Check one):
A w/o emulsion system
112
An o/w emulsion system
Explain your answer to Question 3 (above).
What is the purpose of the propylene glycol in this emulsion?
What effect on water-retaining capacity of emulsions is exhibited by stearyl alcohol?
Provide two (2) advantages of water removable bases:
a.
b.
----------------------------------------------------------------------------------------------------------VII-D.
Prepare 60 grams of Polyethylene Glycol Ointment, N.F. XVI
N.F. Formula
Reduced Quantities
Polyethylene Glycol 3350...........
400 gm
gm
............PolyethyleneGlycol400
600 gm
gm
..............................Tomake
gm
Procedure:
Heat the two ingredients on a water bath to 65° C.
Allow the system to cool, and stir until congealed.
If a firmer preparation is desired, replace up to 100 gm of polyethylene glycol 400 with an
113
equal amount of polyethylene glycol 3350.
Package the ointment in a 1-oz. ointment jar.
Label the product with its official name.
Also, add the auxiliary label: “EXTERNAL
USE”. Discussion:
This ointment base is of the “water-soluble” type and also is of the “greasless” type
since it contains no oils or fats. The PEGs vary in consistency from liquids at room
temperature to solids and so the consistency of the final product can be varied easily by
adjustments in the composition of the formula.
Study Questions
What is the meaning of the numbers associated with the PEGs, e.g. Polyethylene Glycol 3350, 400,
etc.?
Which of the ingredients in this formula above is a liquid at room temperature? (Check one):
Polyethylene Glycol 3350
Polyethylene Glycol 400
Which of the ingredients in this formula above is a solid at room temperature? (Check one):
Polyethylene Glycol 3350
Polyethylene Glycol 400
What number in the PEG formula designation is more, or less, the dividing point between: a Liquid
and solid PEG?
What other dosage form besides ointments use PEGs in combinations as their vehicle or base?
What is the only official (U.S.P.) “Ointment base” preparation in the “water soluble” category?
What factors determine the choice of an ointment base?
114
Product Evaluation
VII-A. White Ointment
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect amount
Incorrect container
Incorrect consistency
Not thoroughly mixed
Ointment around the neck or outside the container
Other
Points
Points
total points for product
*Results in zero points for the entire product.
115
Product Evaluation
VII-B.Cold Cream
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect amount
Incorrect container
Incorrect consistency
Not thoroughly mixed
Ointment around the neck or outside the container
Other
Points
Points
total points for product
*Results in zero points for the entire product.
116
Product Evaluation
VII-C. Hydrophilic Ointment
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect amount
Incorrect container
Incorrect consistency
Not thoroughly mixed
Ointment around the neck or outside the container
Other
Points
Points
total points for product
*Results in zero points for the entire product.
117
Product Evaluation
VII-D. Polyethylene Glycol Ointment
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect amount
Incorrect container
Incorrect consistency
Not thoroughly mixed
Ointment around the neck or outside the container
Other
Points
Points
total points for product
*Results in zero points for the entire product.
118
Laboratory #7 - Ointment Bases
Grade Sheet
Product Points
VII-A
VII-B
VII-C
VII-D
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
Signature of Instructor:
119
PREPARATION OF OINTMENTS: DEMONSTRATION OF THE USE OF OINTMENT MILLS
On a large industrial scale, roller mills are used in the preparation of ointments. The roller mills force
coarsely formed ointments through stainless steel rollers to produce ointments that are uniform in
composition and smooth in texture. In this laboratory exercise, we will use small ointment mills (which are
used in drug product development laboratories and in small-batch product manufacture such as
extemporaneous compounding); its mode of operation is the same as that of roller mills.
THE ONITMENT BASES
1. INDIVIDUAL COMPOUNDING (BY HAND)
VII-A GROUP 1 AND 2
VII-B
VII-C
GROUP 3 AND 4
GROUP
2. USING OINTMENT MILL: ( GROUP COMPOUNDING)
GROUP 1
50GM OF SALICYLIC ACID 6% OINTMENT
SA: 6GM
MINERAL OIL: 5 ML
WHITE PETROLATUM TO MAKE 100GM
GROUP 2
50GM OF HYDROCORTISONE IN AQUAPHOR OINTMENT
HYDROCORTISONE: 10GM
MINERAL OIL: 10ML
AQUAPHOR OINTMENT TO MAKE 100GM
GROUP 3
50 GM OF LIDOCAINE 5% IN PETROLATUM
LIDOCAINE: 5GM
MINERAL OIL: 5ML
WHITE PETROLATUM TO MAKE 100GM
GROUP 4
120
50GM OF IBUPROFEN 10% IN PETROLATUM
IBUPROFEN: 10GM
MINERAL OIL: 5ML
WHITE PETROLATUM TO MAKE 100GM
GROUP 5
50 GM OF KETOPROFEN 10% IN AQUAPHOR
OINTMENT
KETOPROFEN: 10GM
MINERAL OIL: 10ML
AQUAPHOR OINTMENT TO MAKE 100GM
121
Laboratory No. 8
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (87771-336-01)
SEMISOLID DOSAGE FORMS: MEDICATED OINTMENTS
Study Assignment and Background:
th
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7 by Ed., Howard C. Ansel, et.al.
The purpose of this exercise is to become acquainted with the techniques of incorporating various
types of medicinal agents into various types of ointment bases. In doing so, the four (4) types of ointment
bases currently official in the U.S.P. (and prepared in representative form in Laboratory Number 7) will be
used as the bases in four medicated ointments.
GENERAL COMMENTS ON OINTMENT PREPARATION:
th
The following is extracted from Sprowls’ American Pharmacy, 7 edition, pages 263-264 :
“Regardless of the condition of the skin, ointments must be smooth and free from granular or
gritty particles. Therefore, all techniques should be carried out with the express purpose of
having the substances incorporated therein in the finest state of subdivision it is possible to
achieve.
In compounding ointments, the following rules should be observed:
Insoluble substances to be incorporated in ointment bases should always be
in the impalpable powder form.
Insoluble substances are best incorporated when first levigated with a small
portion of the base to form a smooth nucleus and then incorporated into
the remainder of the base.
Water-soluble salts should be incorporated by dissolving them in a small
amount of water and incorporating with the base, using anhydrous lanolin,
if necessary, to absorb the aqueous solution. This method produces a
smooth ointment with a minimum of levigation.
When substances incorporated into ointment bases must be reduced to a fine
state of subdivision, three methods are generally available: (1) use of an
ointment slab and spatula; (2) use of the mortar and pestle; (3) use of an ointment mill.
Ointment Slab. The usual technique consists of rubbing the powder with a
small amount of base until it is thoroughly distributed in a finely subdivided
state, then incorporating this concentrated ointment into the remainder of
the base. Mineral Oil or vegetable oils can be used as levigating agents if
small quantities of medicaments are to be incorporated in the base. The use
of large amounts of levigating agents may result in undue softening of the
finished ointment.
A stainless-steel spatula with a long, broad flexible blade is essential to the
preparation of good ointments. Two spatulas usually are used, one to levigate
the ointment, the other to remove accumulating ointment from the levigating
spatula. Where danger of chemical reaction between the steel spatula and
active ingredients such as iodine, mercury salts, salicylic acid, etc. is a
possibility, a hard rubber spatula or wood tongue depressor should be used.
Mortar and Pestle. It is the general consensus that the mortar and pestle
should be used when large quantities of liquid are to be incorporated into a
base or when exceptionally large quantities of ointment are to be made. The
use of a mortar and pestle is considered not as efficient as the spatula in reducing the size of
122
particles incorporated in or protected by an ointment base because of the small surface area
under levigation at any one time. Then, too, the particles have a tendency the “ride” out from
under the pestle, and the grinding effect is limited. Nevertheless, according to experiments by L.
86
Rosenthaler, the products obtained in either way differ very slightly as to their homogeneity,
provided that the same accuracy has been employed. In these same experiments, he found that 5
minutes of actual rubbing time was necessary to produce homogeneity in products prepared by
either method. However, he does not give any information as to which method is most effective in
the breaking down of agglomerate particles.”
-------------------------------------------------------------------------------------------------------------------VIII-A.
Prepare 30 grams of Sulfur Ointment, U.S.P. XXII
U.S.P. Formula
Reduced Quantities
Precipitated Sulfur.................
100 gm
gm
Mineral Oil.............................
100 gm
gm
White Ointment....................
800 gm
gm
To make
1000 gm
30
gm
[Note: The White Ointment, which each student prepared in Exercise VII-A will be
returned to the same student for use in making Sulfur Ointment, U.S.P. Excess White
Ointment beyond the needs of preparing the 30 grams of Sulfur Ointment, U.S.P. should be left at
the
student’s desk.]
Procedure:
Levigate the sulfur with the Mineral Oil to a smooth paste on an ointment slab.
When uniform, incorporate the White Ointment
Package the ointment in a 1-oz. ointment tube.
Label with the official name.
Include the auxiliary label: “EXTERNAL USE”.
Discussion:
The following information is extracted from the 2
nd
edition of the reference text,
since the current edition has omitted this discussion.
Sulfur Ointment U.S.P.
“Sulfur Ointment, U.S.P., contains 10 percent precipitated sulfur in white
ointment and is prepared with mineral oil as the levigating agent for the
sulfur. Precipitated sulfur is employed rather than sublimed sulfur (also
official) because the former is of finer particle size and results in a smoother
ointment with a greater reactive surface. The ointment is used in the
treatment of ringworm, scabies, and pediculosis. The U.S.P. categorizes
sulfur as a scabicide.”
-------------------------------------------------------------------------------------------------------------
123
Study Questions
Sulfur is official in the U.S.P. in two forms, i.e., Precipitated Sulfur and Sublimed Sulfur.
Precipitated Sulfur is the form recommended for use in ointments. Why?
Which official form of sulfur is also called “Milk of Sulfur”? (Check one):
What is the chief problem in incorporating sulfur into aqueous lotions?
How may the problem in Question 3 (above) be handled, or at least reduced in magnitude?
What is (are) the therapeutic use(s) of Sulfur Ointment?
How much Precipitated Sulfur would be required to make 120 gm of a 15% ointment. SHOW ALL
WORK. Place the answer in the answer box.
Answer
124
------------------------------------------------------------------------------------------------------------
125
-----------------------------------------------------------------------------------------------------------VIII-B.
Prepare the following prescription:
Rx
Cod Liver Oil
Calamine
aa
3|
Burow’s Solution
4|
Aquaphor, qs ad
30 |
ft. ointment; package in ointment jar
sig: Apply t.i.d. s.o.s.
-----------------------------------------------------------------------------------------------------------Procedure:
Levigate, on an ointment slab, the calamine powder into a smooth paste with the
cod liver oil.
Then mix this paste with about one-half of the Aquaphor.
Use the rest of the Aquaphor to incorporate the Burow’s Solution into an emulsion.
Finally, mix the two portions of Aquaphor containing the medicaments into a
homogenous final product.
Package the ointment in a 1-oz. ointment jar.
Label with the usage instructions found in the Sig.
Include an auxiliary: “EXTERNAL USE” label.
Water-in-oil emulsion bases such as Cold Cream, U.S.P., and
Anhydrous bases which contain an emulsifier which permits them to take up
aqueous solution to form water-in-oil emulsions.
In this formula, use is made of the commercially available product called Aquaphor,
which is manufactured by the Beiersdorf Company. This product is anhydrous, but is
described as consisting of “94% petrolatum plus 6% cholesterol esters and cholesterol
alcohol”. These cholesterol derivatives and cholesterol alcohol itself form w/o
emulsions and, in fact, Aquaphor can take up about an equal weight of water (or
aqueous solutions). The Beiersdorf Company also markets a product called Eucerin
which is composed of equal parts of water and Aquaphor worked into a w/o emulsion
and this product also finds use as an ointment base.
-------------------------------------------------------------------------------------------------------------------
126
Study Questions
What is the composition of Hydrophilic Petrolatum, U.S.P. XXII?
Is Hydrophilic Petrolatum, U.S.P. anhydrous? (Check one):
Yes
No
If water is added to Hydrophilic Petrolatum, U.S.P., what type of emulsion is formed? (Check one):
o/w
w/o
What ingredient in Hydrophilic Petrolatum, U.S.P. acts as an emulsifier?
What is the official name of “Burow’s Solution”?
What is the therapeutic effect of “Burow’s Solution”?
-----------------------------------------------------------------------------------------------------VIII-C.
Prepare the following prescription:
Quantities Needed
Rx
Coal Tar
gr =
gr
Zinc oxide
gr =
gr
gr =
gr
Starch
aa
Hydrophilic Ointment*, ad
5%
i
gr =
M. ft. ung. s.a.
Sig: Apply to affected parts h.s.
*Note: The product you prepared in Exercise VII-C will be returned for use here.
Procedure:
On an ointment slab, make a paste of zinc oxide with a portion of the base.
Add the starch with levigation.
Then add the coal tar with levigation.
127
gr
Finally, incorporate the rest of the base with levigation.
Package the ointment in a 1-oz. ointment jar.
Label with the usage instructions.
Include an auxiliary label: “EXTERNAL USE”.
Discussion:
The particular set of ingredients found together in this prescription have often been
prescribed by dermatologists and the final appearance of the product may vary
considerably depending upon the order of mixing. The following is from
nd
“Pharmaceutical Compounding and Dispensing”, 2
edition (Lyman and
Sprowls), page 256:
“Coal Tar . There is a wider variation in preparation of coal-tar ointments
than is to be found in almost any other type of prescription. Two primary
factors influence the physical characteristics of the finished coal-tar
ointment:
the type, the source and the viscosity of the tar employed and
the order of incorporating the ingredients.
The finished prescriptions may vary in color from black, brown, grayish
green to gray. There are 3 methods commonly employed in the
preparation of prescriptions containing the well-known ingredients coal
tar, zinc oxide, starch and a base:
Zinc oxide + coal tar + base + starch.
A black or dark brown ointment is obtained depending on the
coal tar used. It is more difficult to produce a smooth ointment
by this method.
Coal tar + base + zinc oxide + starch.
A grayish green ointment results from this order of incorporation
Zinc oxide + base + starch + coal tar.
A smooth, darker gray product is obtained with this, the most
desirable method of the three for compounding a coal-tar ointment.”
--------------------------------------------------------------------------------------------------------------------Study Questions
The prescription above is not a formula found in the U.S.P., but there is an “official” Coal Tar
ointment, U.S.P. XXII. The following information (below) is extracted from the 2
nd
edition of the reference
book (the current edition has omitted this discussion).
-------------------------------------------------------------------------------------------------------------------Coal Tar Ointment, U.S.P.
“Coal Tar Ointment, U.S.P., contains 1 percent coal tar in a base of zinc
oxide paste. A small amount of polysorbate 80, a non-ionic surfactant, is
employed in the preparation of the ointment and serves a dual purpose. It is
mixed with the coal tar prior to incorporation with the base to increase the
dispersion of the coal tar in the paste and to enhance the removal of the
ointment from the skin during washing. The ointment is employed as an
antieczematic.
Synonym: Unguentum Picis Carbonis.”
128
----------------------------------------------------------------------------------------------------------------a. What is the percent coal tar in the “official” Coal Tar Ointment?
b. Why is Polysorbate 80 included in the formula?
c. What is the therapeutic use of Coal Tar Ointment?
-----------------------------------------------------------------------------------------------------------------Zinc Oxide Ointment, U.S.P.
“In the preparation of Zinc Oxide Ointment, U.S.P., 20 percent zinc oxide
is levigated with mineral oil, and the mixture is incorporated into white ointment. The
ointment is employed topically as an astringent and protective in various skin conditions.”
----------------------------------------------------------------------------------------------------------------Zinc Oxide Paste, U.S.P.
“Zinc Oxide Paste, U.S.P., is prepared by levigating and then mixing 25
percent zinc oxide and starch with white petrolatum. The product is very firm
and difficult to manipulate with a spatula. It is capable of absorbing moisture
to a much greater extent than zinc oxide ointment and is employed as an
astringent and protective. The paste also frequently serves as a vehicle for
other medicinal substances.
Synonyms: Lassar’s Plain Zinc Paste; Lassar’s Paste.”
-------------------------------------------------------------------------------------------------------------Does Coal Tar Ointment utilize Zinc Oxide Ointment or Zinc Oxide Paste as the “vehicle”? (Check
one):
Zinc Oxide Ointment
Zinc Oxide Paste
How do Zinc Oxide Ointment and Zinc Oxide Paste differ from each other in zinc oxide
content? (See above).
What powdered ingredient besides Zinc Oxide included in Zinc Oxide Paste?
129
What is the therapeutic use of Zinc Oxide Ointment?
What is the therapeutic use of Zinc Oxide Paste?
How do Zinc Oxide Ointment and Zinc Oxide Paste differ in their capacity to absorb moisture?
-------------------------------------------------------------------------------------------------------VIII-D.
Prepare the following prescription:
Rx
Benzoic acid
6%
=
gm
Salicylic acid
3%
=
gm
*PEG Ointment, ad
100% =
M. ft. ung., mitte
gm
30 gm
Sig: Whitfield’s Ointment, U.S.P. XVI
*Note: The product you prepared in Exercise VII-D will be returned for use here.
--------------------------------------------------------------------------------------------------------------Procedure:
Reduce the acids to a fine powder with trituration.
Incorporate the acids with part of the PEG Ointment until a smooth, homogeneous
mixture is obtained.
Add the remainder of the PEG Ointment and mix.
Package in 1-oz. ointment jar.
Label with the product name.
Include the auxiliary label: “EXTERNAL USE”.
130
Discussion:
The base used in this formula is of the water-soluble type. The U.S.P. XXII recognizes a product
called “Benzoic and Salicylic Ointment”, but does not specify an ointment base and describes the
product only as follows:
“Benzoic acid and Salicylic Acid, present in a ratio of about 2 to 1 in a suitable ointment base.”
However, the formula in the prescription filled above was official in U.S.P. XVI as
“Whitfield’s Ointment” and the extract below is taken from Remington’s Pharmaceutical
th
Sciences, 14 edition, page 1262, and provides information as to the use of this type of medication:
“Benzoic and Salicylic Acid Ointment U.S.P. XVI.
[Whitfield’s Ointment] - An ointment consisting of benzoic acid (60 Gm), salicylic acid
(30 Gm), and polyethylene glycol ointment (qs) to make 1000 Gm.
Uses: It was formerly very widely employed as a keratolytic and fungistatic agent and is still
frequently prescribed today, despite the advent of undecylenic acid. It is used in the treatment
of epidermophytosis and ringworm of the scalp. Salicylic acid is the principal active ingredient
(see Salicylic Acid, Page 781). In veterinary use it is employed for the treatment of ringworms.”
MEDICATED OINTMENTS AND CREAMS
COMPOUNDING (BY HAND)
All groups will prepare cold cream (Exercise VII-B)
Group 1: VIII-A.
Group 2: VIII-B.
Group 3: VIII-C.
Group 4: VIII-D
Group 6: VII-D
COMPOUNDING USING OINTMENT MILL: GROUP COMPOUNDING
GROUP 5
50GM OF SALICYLIC ACID 6% COLD CREAM
SA: 6GM
MINERAL OIL: 5 ML
COLD CREAM
TO MAKE 100GM
131
GROUP 4
50GM OF HYDROCORTISONE IN EUCERIN CREAM
HYDROCORTISONE: 10GM
MINERAL OIL: 10ML
EUCERIN CREAM TO MAKE 100GM
GROUP 2
50 GM OF LIDOCAINE 5% IN COLD CREAM
LIDOCAINE: 5GM
MINERAL OIL: 5ML
COLD CREAM TO MAKE 100G
GROUP 3
50GM OF IBUPROFEN 10% IN EUCERIN CREAM
IBUPROFEN: 10GM
MINERAL OIL: 5ML
EUCERIN CREAM TO MAKE 100GM
GROUP 1
50 GM OF KETOPROFEN 10% IN COLD CREAM
KETOPROFEN: 10GM
MINERAL OIL: 10ML
COLD CREAM TO MAKE 100GM
Study Questions
1. According to Remington’s Pharmaceutical Sciences,
18th edition, what concentration
of salicylic acid is used in ointments when keratolysis is desired as the effect?
According to the same reference, what concentration range of salicylic acid is used in
ointments when a caustic effect is desired?
What is the concentration of salicylic acid in Salicylic Acid Collodion, U.S.P. XXII?
132
range
What other “dermatological” dosage forms of salicylic acid is official in the U.S.P.? Name three (3)
such forms.
Why is PEG Ointment particularly desirable as a base for ointments applied to the scalp?
6.
What problem may the addition of this chemical present when the capsule is
administered?
Study Questions - Ointment Preparation
th
What is levigation? (Remington: The Science and Practice of Pharmacy, 19 ed.)
What are the three (3) methods of incorporating substance into ointment bases?
a.
b.
c.
How are water soluble salts incorporated into ointments?
Before incorporating insoluble substances into ointment bases, they should first be reduced to
form.
When should a mortar and pestle be used to prepare an ointment?
133
When is it appropriate to use a hard rubber spatula instead of a steel spatula?
134
Product Evaluation
VIII-A. Sulfur Ointment
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect amount
Incorrect container
Incorrect consistency
Not thoroughly mixed
Ointment around the neck or outside the container
Other
Points
Points
total points for product
*Results in zero points for the entire product.
135
Product Evaluation
VIII-B. Ointment
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect amount
Incorrect container
Incorrect consistency
Not thoroughly mixed
Ointment around the neck or outside the container
Other
Points
Points
total points for product
*Results in zero points for the entire product.
136
Product Evaluation
VIII-C. Coal Tar Ointment
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect amount
Incorrect container
Incorrect consistency
Not thoroughly mixed
Ointment around the neck or outside the container
Other
Points
Points
total points for product
*Results in zero points for the entire product.
137
Product Evaluation
VII-D. Whitfield’s Ointment
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect amount
Incorrect container
Incorrect consistency
Not thoroughly mixed
Ointment around the neck or outside the container
Other
Points
Points
total points for product
*Results in zero points for the entire product.
138
Laboratory #8 - Ointment Bases
Grade Sheet
Product Points
VIII-A
VIII-B
VIII-C
VIII-D
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
Signature of Instructor:
139
Laboratory No. 9
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (80313-221-01)
SUPPOSITORIES
Study Assignment and Background:
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7th by Ed., Howard C. Ansel.
The purpose of this exercise is to learn and understand the preparation, properties and dispensing of
suppositories.
Definitions:
Suppositories are solid bodies of various weights and shapes adapted for introduction into the
rectal, vaginal or urethral orifice of the human body. Suppositories melt, soften or dissolve at body
temperature or in the fluids of the cavity into which they are introduced. A suppository may act as a
physical barrier or palliative to the local tissues at the point of introduction or as a carrier of therapeutic
agents for systemic or local action.
Suppository Bases - analogous to the ointment bases, suppository bases play an important role in the
release of the medication they hold and therefore in the availability of the drug for absorption for systemic
or localized effect. For most purposes, it is convenient to classify suppository bases according to their
physical properties, i.e.:
Fatty Bases Cocoa butter-bases
Cocoa butter substitutes-bases
Water-Soluble Bases
Polyethylene Glycol bases
Surfactant bases
Preparation of Suppositories:
Three (3) methods of preparation can be used for the extemporaneous preparation of
suppositories:
a. Hand rolling
Compression
Fusion (Molding).
In this laboratory exercise, one set of suppositories will be made by hand rolling, and
two sets by molding.
140
IX-A.
Glycerin Suppositories, U.S.P. XX
U.S.P. Formula
Amounts for 25 gram formula
Glycerin...............
91 gm
gm
Sodium Stearate......
9 gm
gm
Purified Water........
5 gm
gm
To make...............
100 gm
25 gm
----------------------------------------------------------------------------------------------------------Procedure:
Heat the glycerin in a 50 mL beaker to about 120° C.
Dissolve the sodium stearate, with gentle stirring, in the heated glycerin.
Then add the purified water.
Mix, and immediately pour the hot mixture into a suitable mold.
Cool to permit the suppositories to solidify before removal.
Dispense six suppositories in a one-oz. ointment jar.
Label with the official name.
Use the following auxiliary labels:
NOT TO BE
TAKEN BY MOUTH
For Rectal Use
ONLY
Study Questions
In what two (2) forms (or types) are glycerin suppositories commercially available?
How do these two forms differ in shape?
141
What is the therapeutic use of glycerin suppositories?
How does the glycerin contribute to this therapeutic effect?
What is the purpose of the sodium stearate in the formula?
Why should Glycerin Suppositories be dispensed in “tight” containers?
---------------------------------------------------------------------------------------------------------------IX-B.
Aspirin Suppositories, 325 mg
Six aspirin suppositories will be dispensed, each containing 325 mg of drug, using the
fusion method. The fusion method (or molding) of preparation requires that the
suppository mold be “calibrated” or “standardized” with the base to be used. The
calibration should be first a “calibration by weight” which can be converted into a
“calibration by volume”. The reference book describes the process as follows:
“The first step in the calibration of a mold is to prepare molded suppositories from base material
alone. After removal from the mold, the suppositories are weighed, and the total weight and the
average weight of each suppository are recorded (for the particular base used). To determine the
volume of the mold, the suppositories are then carefully melted in a calibrated beaker, and the
volume of the melt is determined for the total number as well as for the average of one
suppository.”
------------------------------------------------------------------------------------------------------------For the molds used in this exercise, the calibration has already been done with the
following results:
One cocoa butter suppository weighs 1.89 gm and has a volume of 2.08 mL.
The above data can now be used to prepare aspirin suppositories, 325 mg., which
although their individual weights cannot be predicted in advance, their individual
volumes will be 2.08 mL. However, since significant loss occurs in preparing
142
suppositories by the fusion method and since the molds must be “overfilled” to make
an acceptable product, it is necessary to prepare extra formula beyond that needed to
exactly produce the number of suppositories needed. In the current case, six
suppositories are to be dispensed, but the formula for nine will be made. Therefore,
Aspirin needed:
9 suppositories @ 0.325 gm = 2.925 gm ASA
Volume of 9 suppositories @ 2.08 mL = 18.72 mL ≈ 19.0 mL
Procedure:
Lubricate a suppository mold with mineral oil and set aside to chill in the refrigerator.
Calibrate a 50 mL beaker carefully to 19.0 mL with water, drain, and dry.
Place 2.925 gm of aspirin in the calibrated beaker.
Weigh 25* gm of grated cocoa butter in a 100 mL beaker and melt the cocoa butter
to a “creamy” appearance (NOT A CLEAR MELT) by holding the beaker in warm water while
stirring the cocoa butter with a small spatula.
[Note: Be sure to work out the “lumps” in the cocoa butter.]
Pour enough of the melt into the beaker with the aspirin until the contents are
about half way to the 19.0 mL calibration mark.
Thoroughly mix the melt and the aspirin.
Q. s. to the 19.0 mL mark with more melt and thoroughly mix.
*Note: 25 gm is used here as an “arbitrary” figure which is expected to provide more than
enough melt to q.s. the formula to 19 mL. The data above indicate that 9 suppositories @
1.89 gm of pure cocoa butter = 17.0 gm of base needed without allowance for the aspirin
present. But since some excess melt is desired to “overfill” the mold, 25 gm should be an
adequate excess.
Pour the aspirin-containing melt into the chilled suppository mold in a steadystream,
moving from cavity to cavity. Slightly overfill each cavity to allow for contraction of the mix.
Chill in a refrigerator about 15 minutes, then shave off the excess fill, then place in an ice bath
for about an hour to permit maximum contraction; remove from the mold and
weigh six suppositories; i.e.,
Mold #:
6 Aspirin Suppositories weigh =
gm
Average weight of one suppository =
gm**
143
Package six suppositories in a “divided” suppository box and label:
Aspirin Suppositories, 325 mg
Include the following labels
NOT TO BE
TAKEN BY MOUTH
For Rectal Use
ONLY
**Note: the information obtained from these weight measurements now provides information such that
future batches of this formula in this mold could be made by weight by means of the following
calculations:
Average weight of one suppository (from 9.
gm
above) =
Weight of aspirin in one suppository =
0.325 gm
Difference in above = Weight of Cocoa Butter in
gm
each suppository
Clearly, by multiplying the number of suppositories to be made in any future batch by
0.325 gm aspirin/suppository and the number of grams of cocoa butter/suppository, one
could obtain the quantities of base and drug needed for melting, and pouring into the
mold without any further volume calibration of the mixing container.
Study Questions
What are the common alternative names for cocoa butter? Name three (3) such.
What may happen if the melt is not near the congealing point when pouring a formulation which
contains suspended material?
144
Why must pouring into the mold be continuous when using the fusion process?
Would you fill this formulation for a patient currently taking warfarin? (Check one):
Yes
No
Explain your choice.
What is the mechanism of action for ASA suppositories and where are they stored in the
pharmacy?
----------------------------------------------------------------------------------------------------------IX-C.
Aminophylline Suppositories, 0.5 gm
In this part of the exercise, three aminophylline suppositories will be made by a handrolling process in accordance with the following prescription:
Rx
Quantity needed in R x
Aminophylline
0.5 gm
gm
Cocoa butter, q.s. ad
2.2 gm
gm
M. ft. 1 suppository; d.t.d. No. 3
Label:
Aminophylline Suppositories, 0.5 gm
------------------------------------------------------------------------------------------------------------Procedure:
Weigh out the required amount of shredded (or grated) cocoa butter.
Weigh out the aminophylline and powder in a porcelain mortar.
145
Add an equal amount of the grated cocoa butter to the aminophylline
and knead with the pestle in the mortar until uniformly mixed.
Continue to add the remainder of the cocoa butter in geometric proportions
until all has been added and well mixed.
Knead until a cohesive, plastic mass is formed. Remove the mass from the
mortar and knead with the hands for a short time until the mass is plastic,
then form into a crude cylinder. If one desires, the mass may be kneaded
through a piece of filter paper.
Using a pill tile (ointment slab) and a small roller (or spatula), form a uniform cylinder
the diameter of the completed suppository. Excessive pressure will cause the
cylinder to split; insufficient pressure will cause the cylinder to be uneven or hollow.
Use starch as dusting powder if necessary.
Place the cylinder against a measuring device and mark off three segments
of equal length. Using a razor blade, carefully cut off the segments. If properly cut,
one end will become the base of the completed suppository.
Shape the remaining end of the segment to a tapered point.
Place in a suppository box and label with the product name and strength.
Include the following labels: “FOR RECTAL USE ONLY” and
“NOT TO TAKEN BY MOUTH”.
Study Questions
What are the therapeutic uses of aminophylline? Name three (3) such uses.
What two (2) chemical entities are combined to form aminophylline?
What two (2) strengths of aminophylline suppositories are commercially available and provide the
equivalent strength of theophylline?
What percent is theophylline to aminophylline?
146
147
General Study Questions
List four (4) general specifications that an ideal suppository base should meet. (Remington: The
Science and Practice of Pharmacy, 19
th
ed., p.
1592) a.
b.
c.
d.
2. The U.S.P. describes adult rectal suppositories as weighing about
rectal suppositories usually weigh
gm each. Infant
that of adult suppositories. (Remington: The
th
Science and Practice of Pharmacy, 19 ed., p. 1591)
From what suppository base are water soluble drugs more readily released in the body?
th
(“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7 ed.)
Fat soluble drugs are released more readily from what type of ointment bases?
th
(“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7 ed.)
148
149
The compression process is especially suited for: (“Pharmaceutical Dosage Forms and Drug
Delivery Systems”, 7
th
ed., for questions 5 and
6) a.
b.
What are two (2) disadvantages of the compression process?
a.
b.
Dr. Jones calls you to say that a 60 lb child is in his office suffering from nausea and vomiting. She
wants to write a prescription for Phenergan Suppositories™ but needs to know what strength she
should write. Knowing that the dose is 1 mg/kg and that Phenergan Suppositories™ are available in
12.5 mg and 25 mg sizes, which one would you recommend? SHOW ALL CALCULATIONS.
150
Product Evaluation
IX-A. Glycerin Suppositories
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect size
Incorrect container
Cracked suppository
Other
Points
Points
total points for product
*Results in zero points for the entire product.
151
Product Evaluation
IX-B. Aspirin Suppositories
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect size
Incorrect container
Cracked suppository
Not thoroughly mixed
End not shaved
Other
Points
Points
total points for product
*Results in zero points for the entire product.
152
Product Evaluation
IX-C. Aminophylline Suppositories
Label
Incorrect Sig
Type overs/erasers
Crooked label
No tape
Crooked tape
Wrinkled tape
Dirty/Fingerprints
Place incorrectly on container
*Incorrect label on product
No auxiliary label (if required)
Other
Product
Incorrect size
Incorrect container
Cracked (split) suppository
Hollow suppository
Improper shape
Other
Points
Points
total points for product
*Results in zero points for the entire product.
153
Laboratory #9 - Suppositories
Grade Sheet
Product Points
IX-A
IX-B
IX-C
Total Points
Laboratory Report
Points
Work Area unclean (-5 Points)
Late Completing Laboratory (-5 Points)
Report Turned in Late (-10 Points)
Total Points Earned
Signature of Instructor:
154
Laboratory No. 10
NAME
DESK No.
Date
PHARMACEUTICAL COMPOUNDING LABORATORY (80313-221-01)
STERILE PRODUCTS: PARENTERAL AND OPHTHALMIC PRODUCTS
Study Assignment and Background:
th
“Pharmaceutical Dosage Forms and Drug Delivery Systems”, 7 Ed., by Howard C. Ansel, et. al.
The purposes of this exercise are to become familiar with the:
preparation and packaging of pharmaceutical products which are sterilized by
thermal and membrane filtration methods; and
use of aseptic handling techniques in handling sterile products and utensils in a
laminar flow hood work station.
----------------------------------------------------------------------------------------------------------------X-A.
Ephedrine Sulfate Injection, 25 mg/mL
In making this preparation, an aqueous solution of a drug and added substances will be prepared
under non-sterile conditions in an ordinary laboratory environment, packaged in a rubber-stoppered
“serum vial” then sterilized in a steam autoclave at 121° C for 20 minutes exposure time at 15 lb/sq. in.
of pressure.
Prepare the following solution at your desk:
Note:
Ephedrine Sulfate
750 mg
Benzalkonium Chloride Solution, 0.015%
20 mL
Sodium Chloride Solution, 0.9% q.s. ad
30 mL
This solution is isotonic due to the presence of the ephedrine sulfate and
sodium chloride, disregarding the benzalkonium chloride solution.
Procedure:
Filter the solution through filter paper into a 30 mL “serum vial” which has been
well rinsed with distilled water; cap the vial with a rubber stopper and metal seal as
demonstrated in class.
Place you name IN PENCIL (ink will “blot” and become illegible in the autoclave) on
a stringed tag, affix the tag to the neck of the vial and submit for sterilization in the
autoclave.
When the vIal has been sterilized, place a label on it containing the following:
“Ephedrine Sulfate Injection 25 mg/mL
Contains:
Benzalkonium Chloride
Sodium Chloride 0.3%”
155
0.015%
Study Questions
The concentration of Benzalkonium Chloride in Preparation X-A. is 0.015%. Express this
concentration as:
a. ppm:
b. ratio strength:
mg-%
The isotonic sodium chloride solution used in Preparation X-A. is 0.9%. The sodium chloride
equivalent of KCl is 0.76, what % KCl would be isotonic with blood serum and similar biological fluids?
Express 121° C (the sterilization temperature in this exercise) as ° F.
156
Provide two (2) names, manufacturers and ratio strength of commercially available Benzalkonium
chloride that can be purchased over-the-counter?
Name
Manufacturer
5. Complete the following: Ephedrine Sulfate is
less
shorter
Ratio Strength
longer (check one) acting, but
more (check one) potent than epinephrine.
What is the mechanism of action of Ephedrine Sulfate and which type of adrenergic receptors does it
effect?
------------------------------------------------------------------------------------------------------------------X-B.
Sterile Phenobarbital Sodium, U.S.P. XX
The U.S. Pharmacopeia recognizes five distinct classes of sterile preparations for
parenteral use, one of which is described as:
“dry solids or liquid concentrates containing no buffers, diluents, or other
added substances, and which, upon the addition of suitable solvents, yield
solutions conforming in all respects to the requirements for Injections, and
which are distinguished by titles of the form, Sterile
.”
------------------------------------------------------------------------------------------------------------The product prepared in this part of the experiment is of this class in that dry, powdered
sodium phenobarbital will be placed in a “serum vial” and heat sterilized by dry heat at
160-170° C, then the vial will be sealed with the appropriate closure which has been
sterilized separately by steam sterilization. The stopper will be aseptically affixed to the
vial in a laminar flow hood.
Prepare the following:
Weigh 1.20 gm of sodium phenobarbital and place it in a dry 30 mL “serum vial”.
Temporarily seal the orifice of the vial with aluminum foil, affix a stringed tag with
your name on it and submit it for dry heat sterilization for 1 hour at 160-170° C.
After the vial has been heat sterilized, take it (with the aluminum foil cap still
in place) to the laminar flow hood in the Dispensing Laboratory.
157
Using demonstrated technique, remove the aluminum foil with sterilized forceps,
and place a rubber closure* in the orifice of the vial using the sterilized forceps.
Then place the metal sealing cap on the rubber closure and crimp it around the
closure, using the crimping pliers.
*Rubber closures will be provided to you in a sterile condition from previous processing in a
steam sterilizer. The rubber will withstand the temperatures of a steam sterilizer but is
degraded by the temperatures used (160-170° C) in the dry heat sterilization of the sodium
phenobarbital.
Label the finished vial with the following:
“Sterile Phenobarbital Sodium, U.S.P. XX 1.2 gm”
Note: At the time of use, the Sterile Phenobarbital Sodium prepared above would have to be
“reconstituted” with Sterile Water for injection, U.S.P., in order to obtain a solution of the drug for
parenteral use. If 20 mL of such solvent were added to the vial prepared above, the resulting
solution would have a concentration of 60 mg/mL.
Study Questions
The molecular weight of sodium phenobarbital is 254 and its formula is C12H11N2O3Na. The
molecular
formula for phenobarbital is C12H12N2O3. The vial of sodium phenobarbital prepared in
this experiment contains 1.2 gm of drug.
To how much phenobarbital is this quantity equivalent:
[Atomic weights: C = 12; H = 1; N = 14; Na = 23; O = 16]
Assume that 20 mL of Sterile Water for Injection were added to the contents of the vial prepared in
X-B. and that the resulting solution also has a volume of 20 mL. In such case, would the resultant
solution be hypotonic, isotonic or hypertonic? (Check one):
hypotonic
isotonic
hypertonic
Show calculations to prove your answer to Question 2 (above). (Sodium chloride equivalent of
sodium phenobarbital = 0.24)
158
th
According to page 1067, Remington’s Pharmaceutical Sciences, 17 edition, what are two (2)
general therapeutic uses of intravenous phenobarbital?
a.
b.
What two (2) types of seizures is parenteral phenobarbital indicated for?
----------------------------------------------------------------------------------------------------------X-C.
Atropine Sulfate Ophthalmic Solution, 1%
Solutions prepared from non-sterile ingredients under non-sterile conditions can be sterilized without the
use of heat by filtering the solution through a “membrane filter” whose pore size is smaller than that of the
pathogens which can be removed. These pathogens are bacteria, yeasts, fungi, and protozoans larger
than about 0.3 µ in diameter since the smallest pore size used in most filtration systems intended for
sterilization is 0.2 µ in diameter. Consequently, viruses are not removable by membrane filtration.
In this preparation, the solution will be prepared in the regular laboratory work area from non-sterile
ingredients, then filtered through a membrane filter in a device called a “Nalgene Filter Unit” in which the
sterilized filtrate is collected in a lower, pre-sterilized closed container with a sterile pouring spout. This
sterilized solution will then be transferred by aseptic means into sterilized dropper bottles in the laminar
flow hood work station.
Working in assigned groups, prepare the following:
Atropine sulfate
0.600 gm
Sodium chloride
0.460 gm
Benzalkonium chloride Solution, 0.015%
40.000 mL
Distilled water, q.s. ad
60.000 mL
Procedure:
Filter the prepared solution through a “Nalgene Filter Unit” containing a
membrane filter with 0.2 µ pore size using the procedure demonstrated in class.
159
Each student in the group should fill a 1/2 ounce dropper bottle by aseptic transfer
of the filtered solution from the “Nalgene Filter Unit” into the bottle performing the transfer in
a
laminar flow hood, using demonstrated techniques.
Label each bottle as follows:
“Isotonic Atropine Sulfate Solution, 1%
(contains 1:10,000 Benzalkonium Chloride)”
4.
Use the auxiliary label:
“NOT TO BE TAKEN BY MOUTH”.
Study Questions
What would be the ratio strength of the benzalkonium chloride in the finished product in X-C.?
If the sodium chloride were replaced with sodium nitrate in X-C, how many grams of sodium nitrate
would be needed to have the same effect on the solution’s colligative properties as are produced by
the sodium chloride?
[Sprowl’s Values:
V = 33.3 for NaCl;
V = 22.7 for NaNO3)
What effect on the eye would administration of this atropine sulfate solution have as
eye drops?
160
How would you counsel a patient with a prescription for these eye drops?
Describe the solubility of atropine sulfate in:
water:
alcohol:
glycerin:
Provide three (3) names and manufacturers of commercially available atropine sulfate (1%)
solution?
Name
Manufacturer
[ ] Brackets denote revised wording based on updates in professional terminology
161