Fundamentals of:
Pharmaceutics 1
Prepared by:
Dr. Heba Al-Saleh
Dr. Amani Al-Sakarneh
1
Detailed Course Description
Unit
number
Unit name
Unit content
• Definition of:
Pharmacy, pharmacist,
pharmaceutics,
Medication, controlled
Substances,
pharmaceutical dosage
forms, pharmaceutical
preparations.
• Pharmacist role in
health care
• Pharmacist
technician role in
health care
• Types of pharmacy
practice setting:
(community
pharmacy, non
institutional ,drug
stores, institutional
pharmacy such as
hospital pharmacies,
drug manufacturing,
medical
representation,
academic field ,
governmental
institution)
• Pharmacist and
Pharmacist relation
introduction
1.
2.
Pharmaceutical
ethics and
behavioral aspects
2
Time
needed
• Pharmacist and
Patient relation
• Pharmacist and
Community relation
• Pharmacist and
Physician relation
• Logos of Medical
profession
• Social and
behavioral aspects of
pharmacy
• General
pharmaceutical ethics
• Definition of
prescription.
• Types of
prescriptions and
criteria to dispense it.
• The parts of
prescription
• Abbreviations.
• Measures taken to
deal with any mistake
in any prescription
• Physical procedures:
(size reducing,
separation, Mixing
and homogenization
• Pharmaceutical
procedures that need
heat, cold like
(crystallization,
lyophylization,
drying, melting,
of pharmacy
3.
Dispensing and
Prescription.
4.
Physical
pharmaceutical
procedures
3
evaporation, boiling,
viscosity).
5.
6.
• Dissolving :
• Methods of dissolving,
and types of solvent
• Distillation
• Extraction
• Maceration
• Decoction
• Percolation
• Digestions
▪
Definitions.
▪ Routes of drug
administration.
▪ Pharmaceuticals
dosage forms.
▪ Pharmacokinetics (in
brief)
▪ Bioavailability,
Bioequivalence,
▪ pharmaceutical
equivalence.
Pharmaceutical
procedures which
need solvents
Biopharmaceutics
And
pharmacokinetics
Evaluation Strategies:
Exams
Percentage
Date
Mid Exam
40%
--/--/----
Final Exam
50%
--/--/----
4
Homework and
Projects
Discussions and
lecture
Presentations
10%
--/--/----
Teaching language:
• English
Teaching Methodology:
▪ Lectures
Text Book References:
1. Pharmaceutical practice , A.J. Winfield, R.M.E. Richards, 3d. edition,
2005, Churchill
Livingstone
2. Remington ,The science and practice of pharmacy 21st edition,2004,
Lippincott William &
Wilkens
3. British Pharmacopoeia 2008, British pharmacopoeia Commission,
TSO.
4. L V Allen, N G Popovich, H C Ansel, Ansel‟s Pharmaceutical dosage
forms & Drug Delivery Systems, 9th edition, 2nd Indian reprint, 2011,
Published by Lippincott Williams and Wilkins, Wolters Kluwer (India)
Pvt. Ltd., New Delhi.
5. The pharmacy technician work book & certification , Perspective
press ,2nd edition 2004,
Morton publishing company.
6. The Science of dosage form design, Edin burgh, 2002, New Yourk,
Churchill Livingston
5
CHAPTER 1
INTRODUCTION TO
PHARMACEUTICS
6
Definitions:
- Drug:
it is any substance or mixture of substances from animal, plant,
mineral sources, or synthetic compounds used in the diagnosis,
prevention of disease, or to relieve symptoms, ease pain or cure
disease.
- Pharmaceutics:
it is that part of pharmacy science that is interested in the study of
drugs for their physical properties, stops in manufacturing and
preparing different pharmaceutical dosage forms and factors that
effect to aim the best results when using this drug (medicine).
- Pharmaceutical dosage form:
we mean the pharmaceutical form of drugs which are dispersed to
the patient, to be administered in a certain way in order to get the
desired effect, example tablets, syrups, or ointments……..ect.
- Pharmaceutical preparation (pharmaceutical specialty):
this is ready prepared form, containing active constituents, and
prepared in its final form to be dispersed to the patients, these are
prepared in pharmaceutical forms.
- Poison:
any agent capable of producing a deleterious response in a
biological system, it may cause death.
- Crude drug: it is a crude substance obtained from animal, plant,
or mineral sources used in preparing drugs.
7
- Pharmacist: the person who is licensed to practice pharmacy
profession.
- Pharmacy:
it is the place designed and furnished to practice pharmacy
profession.
-Pharmacist role in health care :
A scope of the pharmacist work:
The pharmacist plays an important role in the community of
health care, and preserves high standards in the health care
system society, in supporting the doctors, nurses, and also other
health care staff , LIKE:
a- Working in public pharmacy or in private pharmacy: here his
major task is in dispensing the correct drugs (medicines) to the
patient, according to a written medical prescription, guiding
(directing) the patient in the correct way of drug administration,
in order to achieve the best results.
Also he should observe the effect of the drugs effect upon the
patient, also among his duties is to conduct health care
education and basic health care services such as first aids to the
public and dispensing simple drugs without prescriptions
(Over-the-counter drug)(O.T.C), also supporting medications and
appliances such as baby health foods and mother and baby
health care programs…..etc.
b- Working at pharmaceutical drug industry: there are various
fields of responsibility undertaken by the pharmacist in the
pharmaceutical firm. He supervises all the product processes. He
8
is responsible in the analysis and quality control procedures.
Responsible distributing and marketing the pharmaceutical
products, also he is responsible for the riser work and studies
carried in promoting, and improving and raising its standards.
c- Working at scientific medical promotion field: he works in the
field of advising medical, workers of their different specialties
about the pharmaceutical preparations that his drug company is
producing, specially the new products, explaining about their
property characteristics in a faithful truthful scientific manner.
d- Working at the academic teaching field: specialized
pharmacists holding higher education degrees (diploma), work in
the teaching profession of different pharmaceutical sciences. In
pharmacy faculties at the universities and at the colleges
(intermediate university colleges).
e- Working at the governmental establishments: here
pharmacists work at many field, as drug analysis, also they test
(check up) drugs, in monitoring, registering, also in the
inspection and supervision (control) pharmacies. Controlling the
situation of the profession to raise their scientific levels to reach
in better and fine higher standards. There are other fields so
many of them can work and share in, as in poison control
centers, analysis of drug food, and water…….etc.
9
The associate pharmacist should carry his responsibilities and
committed to the following instructions:
1- He should be committed to his job (task) specifically given to
him by the pharmacist according to the laws and legislations
governing the pharmacy profession.
2- He should wear the white lab coat and keep cleanliness and
tidiness of the pharmacy.
3- Treat the patient by respect, be nice to them and have
patience.
4- Make the patient feel secure and give him the advice and
guidance of correct usage of the medications.
5- He should stick to the official prices of the drug.
6- Obliged to adhere in the methods and known steps in
dispensing the medical prescription and labeling.
7- He should not compound or prepare any kind of medicine
without the direction of the responsible director (the
pharmacist).
8- He should be committed to the job (task) specified to him such
as, he should refuse to sell dangerous (unsafe) drugs.
10
Pharmacist technician role in health
care:
What does a pharmacy technician do?
•
•
•
•
•
•
Under pharmacist supervision, pharmacy technicians:
supply medicines to patients, whether on prescription or over the
counter
assemble medicines for prescriptions
provide information to patients and other healthcare professionals.
Pharmacy technicians also:
manage areas of medicines supply such as dispensing area
supervise other pharmacy staff
produce medicines in hospitals and the pharmaceutical industry.
•
•
•
Where do pharmacy technicians work?
Pharmacy technicians work in many different work environments. These
include:
Community pharmacies (sometimes called retail or high street
pharmacy) and hospitals. Most pharmacy technicians work in
community and hospital pharmacy
Pharmaceutical production or sales in the pharmaceutical industry
-Here are several types of pharmacy, and other places where a
trained pharmacist may work. This includes :
-Community Pharmacy
-Hospital Pharmacy
11
-Clinical Pharmacy
-Industrial Pharmacy
-Compounding pharmacy
-Consulting Pharmacy
-Ambulatory Care Pharmacy
-Regulatory Pharmacy
-Home Care Pharmacy
-Managed care pharmacy
-Research pharmacy
-Specializations in Pharmacy
Some pharmacists may specialize in a certain area of drug therapy with
a master’s degree or other continued learning. This helps them to gain
proficiency and recognition to practice in specialized fields. This may
include areas such as:
•
•
•
•
•
Oncology pharmacy
Nuclear pharmacy
Geriatric pharmacy
Psychopharmacotherapy
Personal pharmacy
12
•
•
•
•
•
Nutritional support pharmacy
Hospice pharmacy
Pediatric pharmacy
Pharmacy benefit manager
Poison control pharmacy
Each of these specializations is a type of pharmacy in its own right,
although such pharmacists usually practice in a hospital pharmacy.
Their unique knowledge base makes it possible for them to provide
medical information in particular relevant situations.
13
14
Chapter 2
pharmaceutical ethics and
behavioral aspects
of pharmacy
15
Relationship between the pharmacist and patients
Patients are more likely to open up and disclose information if
they trust their pharmacist or healthcare professional, and a better
quality of interaction may result in greater patient autonomy and
shared decision-making.
Also: discuss the relationship between:
-Pharmacist and other pharmacists
-Pharmacist and physician
* Pharmacopoeia:
Pharmacopoeia is considered as laws for drugs.
It is obligatory to the state which has published it. It is
implemented on pharmaceutical establishments and institutions in
all its departments according to the law of pharmacy professional
practice.
Pharmacopoeia is edited by a specialized committee, of scientific
officials, comprising group of pharmacists, and physicians, and
the editorial board is also responsible for the advancing the
advancing the pharmacopoeia, renewing, and adding to it the
latest information about new medicinal substance.
The pharmacopoeia is the major reference for preparations and
manufacturing drugs of different pharmaceutical dosage form.
Pharmacopoeia contains complete and sufficient information
especially about every single drug and is interested in different
methods of assays and analysis, to be sure about the purity,
quality, and validity for the usage of drug. Also it contains
16
physical and chemical properties of each chemical and drug
components to make it easier to identify and test for it.
In Egypt the first pharmacopoeia was published in Arabic
language, called Egyptian pharmacopoeia (P.E) there are so many
pharmacopeia published by most of the states of the world.
(WHO) world health organization of the united nation has
published the first united international pharmacopoeia in 1951 by
many different languages and the 2nd edition was published in
1967.
Most of the pharmacopoeia looks like the same in their contents
of information with simple differences in some substances found
in them.
It is important to know that pharmacopoeias do not mention trade
names but is concerned only with scientific names of drugs such
as generic names and chemical names.
* Some examples of pharmacopoeia:
1- British pharmacopoeia (B.P).
2- International pharmacopoeia (I.P).
3- European pharmacopoeia (E.P).
4- United states pharmacopoeia (U.S.P).
The pharmacopoeia which is primarily depended upon
(authoritative) in Jordan is the British pharmacopoeia which
comprises of two volumes; the 1st volume contains
comprehensive information about different medicinal substances.
The 2nd volume contains information about pharmaceutical dosage
forms, method of preparations, and analysis. And at the end of the 2nd
volume there is an alphabetical index for its easy usage.
The considerable number of drugs and of its different type shapes, and of
their trade names it was very important to have another reference book,
17
which contains enough information about drugs especially from
therapeutic point of view for pharmacists and physicians.
For these reasons the council of pharmaceutical society of great British
has published a reference book for these purposes which are called
Martindale extra pharmacopoeia which contains information of official
and nonofficial drugs and even drugs which have been omitted by the
B.P and drugs which have not been registered yet and which are under
research work and study. Also it contains other drugs registered in other
pharmacopoeias other than the B.P.
Logos of Medical profession
Logo of medicine is :
Logo of pharmacy is :
18
General pharmaceutical ethics
Pharmacists are health professionals who assist individuals in making
the best use of medications. This Code, prepared and supported by
pharmacists, is intended to state publicly the principles that form the
fundamental basis of the roles and responsibilities of pharmacists. These
principles, based on moral obligations and virtues, are established to
guide pharmacists in relationships with patients, health professionals,
and society.
I. A pharmacist respects the covenantal relationship between the
patient and pharmacist.
II. A pharmacist promotes the good of every patient in a caring,
compassionate, and confidential manner.
III. A pharmacist respects the autonomy and dignity of each
patient.
IV. A pharmacist acts with honesty and integrity in professional
relationships.
V. A pharmacist maintains professional competence.
VI. A pharmacist respects the values and abilities of colleagues and
other health professionals.
19
VII. A pharmacist serves individual, community, and societal needs.
VIII. A pharmacist seeks justice in the distribution of health
resources.
20
Chapter 3
Dispensing and Prescription
21
The prescription:
The process of drug dispensing is that part of pharmacy practice which
the pharmacist or associate pharmacist, comply to the order of the
physician for the treatment of the patient. And this order mostly is done
by a written form. But sometimes it will take other forms such as
verbally or by the phone. And in all these cases it is better to the
pharmacist to ask the doctor for a written prescription.
If it happens that the pharmacist cannot get a written prescription he
should take care and be very cautious, because at this point the
pharmacist is giving the drug to the patient to be used according to the
pharmacist direction.
The pharmacist should contact the doctor to uncover all the necessary
information concerning to an unclear prescription.
The pharmacist should be ready and willing to answer to any question
the patient may ask him, and should give the necessary advice and
consolation. Also he should advice and gives the necessary consultation
in case of dispensing medicaments without prescription (O.T.C) drugs.
and should be very careful and easier in as much as if he were dispensing
a written prescription.
The prescription can be defined it is a written order from the doctor
to the pharmacist to dispense certain medicaments to the patient in a
known quantity and of a specified mode of usage.
* A model of medical prescription:
Most medical prescriptions have a unified basic shape and are composed
of four major parts.
1- The superscription:
22
It is written( Rx) as it means(take this order) the origin of this symbol
represents, the plant Jupiter, as during the ancient times there was a brute
belief of gods upon the practice of medicine, and the people did not
believe in the necessities and activities of drugs.
A model of medical prescription
Dr. sahar gaith
date: 15/10/2018
General practitioner – 7th circle
Name of the patient: amani .q
age: 25 years old
Rx
Panadol 500 mg
20 tab
2 t.i.d
Rx means in Latin language (recipe) its meaning (take), and there are
some prescriptions such as in France instead of Rx the word (P) is
written and has the same meaning.
2- The inscription:
And it is the body of the prescription and consists the written names of
different medicines in the prescription and their amount (quantity). It
may be kind or more and the ideal types are that it should not be more
than three kinds of drugs.
In the previous model the inscription is:
Panadol
one kind of drug
Quantity
20 tab
23
3- The subscription:
We mean instructions (directions) from the doctor to the pharmacist, to
explain the procedure of dispensing; it may contain one of the following
information or all:
Strength of drug, pharmaceutical dosage form, how many times the
prescription should be repeated, the length of the time to be used, and
other instructions.
In the above model the subscription is:
500 mg =strength
Tab=tablets
4- The signature:
It is the information given to the patient how to use the drug.
In the above model
2 t.i.d (meaning two tablets, three times daily)
there are other information the prescription may contain these are very
important in order to be sure for the accuracy of the prescription.
a- Name and address of the doctor and his specialty.
b- Name and address of the patient and his age.
c- Date of the prescription written.
d- Stamp of the doctor and his signature.
Language of the prescription:
The prescription should be written in a very detailed form and known
language to the pharmacist, as in English or in Arabic. But most of the
times it is written by symbols and these symbols are from Latin language
and are known among the pharmacists and doctors in most parts of the
24
word, and this unifies the language of the prescription internationally,
and makes it easy for uniting in a short and simple manner.
The English language was depended upon in uniting the prescription in
the U.S.P and B.P while the European pharmacopeia still is dependent
on the Latin language and its short symbols, and also many countries are
using these symbols still now, and Jordan is one of these countries.
Also there are so many physicians who use the numbers to express the
uses of drugs such numbers are show in the following example:
Rx
Aspirin 30
Tab.
2x3 P.C
1- The superscription is: Rx.
2- The inscription is: aspirin 30.
3- The subscription is: Tab. (tablets).
4- The signature is: 2x3 P.C (meaning: two tablets three times daily after
meals (food)).
Try to mention every part of those prescriptions:
25
26
* The system of dispensing the medical prescription:
There should be a strict system in dispensing the medical prescription
inorder to be sure of its security, speedy, and of its precision during
dispensing process. There are general rules should be followed in
dispensing process. What so ever of any kind (type) of the prescription,
during the receipt of the prescription we follow the following rules:
1) Read the prescription carefully with attention and you should not
show any doubts to the patient or prescription holder about its
contents, so it may rise doubtfulness or untrusting in the doctor or in the
pharmacist, the pharmacist should not hesitate in asking an advice of any
of his colleagues if needed. And if the drug are not available in his
pharmacy, the prescription should be returned to the patient and guiding
him to the easiest way in getting the drug.
2) Check the dosage and be sure that it is appropriate for the
patient's age and if there is any doubt about its accuracy do not
complete the dispensing of the prescription until revised and confirmed.
And if the dosage may be dangerous or very little so that it may not be
useful do not hesitate in contacting the doctor who has written the
prescription in order to be assured about the dosage.
And if it was impossible to contact the doctor and there was no
indication that the doctor has written this dosage intentionally as if
drawing a line under the dosage, or written it by words (the figures) or
confirming it in the pharmacopoeia, and in this case matter he should
take care specially in the cases that the drugs were prescribed for
children and infants, and to be sure about the age, and calculate the
dosage accordingly.
3) The drug is given to the patient with explanations in a clear
manner and attaching a sticker tag (label) on the drugs packets
written upon it:
27
1- Name of the pharmacy and its address.
2- Name of the patient and his age.
3- Name of the drug and its dosage form.
4- Direction for the use.
5- Registration number in the prescription logbook, then dispensing to
the patient.
4) Register the prescription in appropriate logbook so there should be
two kinds of logbooks:
a- Ordinary prescription logbook.
b- Dangerous drugs prescription logbook.
Especially when it concerns with special prescription, is specified by
pharmacy practice law, which should be followed in its dispensing as it.
5) In the case when the prescription is to be returned to the patient
after dispensing it should be marked upon it in a way to show that it
has been dispensed, such as stamped by pharmacy's stamp.
* Types (kinds) of the medical prescription:
1- Ordinary prescription form.
These prescription are used for most kinds of drugs such as analgesics,
antibiotics, vitamins, antihypertensive drugs, antidiabetic drugs, cardiac
glycoside drugs,……….etc.
And are applied to all drugs that has been mentioned above, in case of
the shape, method of dispensing and may be returned (the prescription)
to the patient after dispensing, so there is no need in keeping it in the
pharmacy, also this kind of prescription are used for the sedative drugs
and used in the treatment of psychological disease, and in this case it
should be registered it in the ordinary registration logbook and stamped
28
in order to be known that it has been dispensed so there is no need in
repeating it.
2- Special prescription form.
This prescription has the same general form which was mentioned before
in addition to it has red ink writing of the phrase (special prescription)
and numbered with serial numbers keeps the physician a copy of it, and
during dispensing it should be registered in the dangerous drug
prescription logbook, and the prescription is kept in the pharmacy for
five years starting from the latest registration and keeping it for five
years and not returning back to the patient and giving him a copy of it in
case he wants a copy, and it is not to be repeated, or else the patient
should get a new prescription from the doctor in case of repeating the
drug, the pharmacist should be aware of the available of the medical
specification condition in the dangerous drug prescription which
are:
1- Should contain all the parts of ordinary prescription.
2- Should be numbered and stamped and have the phrase in red ink
written (special prescription).
3- Should be free from any scratch or manipulation.
4- The amount of the dangerous drugs should be written in numbers and
also in words.
5- Should be dispensed within three days.
6- Should contain an amount of drug not more than for two days.
7- Should contain only dangerous drugs and only one non-dangerous
drug.
8- Should be confirmed that such dangerous drugs are used only for
treatment.
29
Symbols of the medical prescription (abbreviations)
Latin symbol
Latin words
English words
Rx
Aa
Add
Ac
Aq
t.i.d.
Recipe
Ana
-------ante cibom
Aqua
-------
Take
Of each
Add
Before food
Water
Three times daily
b.d (b.i.d)
Susp.
Solv.
C
Aq.dest
p.m
Dil
Pot.
P.O
f.)Ft)
Fort
Phial
Fl
i.c
Emuls
Ovl.
M
bid die
Suspensiones
Solve
Cum
Desillatus
Post meridien
Dilutes
Potion
Per os
Fiat
Fortis
Phial
Fiuidum
Intercibos
Emulsion
Ovulla
Misce
Twice daily
Suspension
Dissolve
With
Distilled
After noon
Diluted
Potion
By mouth
Make
Strong
Bottle
Fluid
Between meals
Emulsion
Ovule
Mix
30
Arabic
words
‫تفضل‬
‫بالتساوي‬
‫اضف‬
‫قبل االكل‬
‫ماء‬
‫ثالث مرات‬
‫يوميا‬
‫مرتان يوميا‬
‫معلق‬
‫اذب‬, ‫حل‬
‫مع‬
‫مقطر‬
‫بعد الظهر‬
‫مخفف‬
‫جرعة‬
‫بالفم‬
‫حضر‬
‫قوي‬
)‫زجاجة(قارورة‬
‫سائل‬
‫بين الوجبات‬
‫مستحلب‬
‫بيضة‬
‫امزج‬
m.d
more dicto
As directed
En
Mitt
Ol.
O
Auri
Elix
Cap
Colon
neb.
Agit
aq.bull
Gtt
Liq
Lin
Lot
Tinc
Mist
Collyr
Ocul
Tabl
Past
Non.rep
Pulv
Cap.amylae
Ung
Amp
Ad
Enema
Mitte
Oleum
Os
Auristillae
Elixiria
Capsula
Collutorium
Nebula
Agitur
-------Gultae
Liquor
Linimentum
Lotio
Tincture
Mistira
Collyrium
Oculentom
Tabulatta
Pasea
Ne repeater
Puvis
Capsula amylae
Unguentom
Ampulla
Addantur
Enema
Send
Oil
Mouth
Ear drop
Elixir
Capsule
Nose wash
Spray
Shake
Boiling water
Drops
Liquid
Liniment
Lotion
Tincture
Mixture
Eye drops
Eye ointment
Tablet
Paste
Don’t repeat
Powder
Cachet
Ointment
Ampul
Up to
a.c
Cont
I.v
Anticibom
Contra
______
Before food
Against
Intravenous
31
‫حسب‬
‫االرشادات‬
‫رخصة‬
‫ارسل‬
‫زيت‬
‫فم‬
‫قطرة اذنية‬
‫أكسير‬
‫محفظة‬
‫غسول انف‬
‫رذاذ‬
‫ خض‬,‫رج‬
‫ماء مغلي‬
‫قطرات‬
‫سائل‬
‫مروخ‬
‫غسول‬
‫صبغة‬
‫مزيج‬
‫قطرة عينية‬
‫مرهم عيني‬
‫قرص‬
‫معجون‬
‫ال تكرره‬
‫مسحوق‬
‫برشامة‬
‫مرهم‬
‫امبوله‬
‫حتى يصبح‬
‫المقدار‬
‫قبل الطعام‬
‫ضد‬
‫في الوريد‬
S.C
p.c
a.m
Ss
I.m
q.m
s.o.s
Indies
q.d
q.h
o.d
q.n
Pil
Suppose
p.r.n
Garg
Q
Sol
q.s
Lev.
Mag.
______
Postcibom
Ante meridien
Semisse
____
quaque mane
Si opussi
Indies
quaert dic
quaque horae
Oomnidie
quaque nocte
Pilulla
Suppositoria
Prorenata
Gargarisma
Quaque
Solution
Quantum
sufficiat
-------Magnum
32
Subcutaneous
After food
Before noon
Half
Intramuscular
Every morning
If necessary
Daily
Four time daily
Every hour
Every day
Every night
Pill
Suppository
Occasionally
Gargle
Every
Solution
Sufficient quantity
‫تحت الجلد‬
‫بعد الطعام‬
‫قبل الظهر‬
‫نصف‬
‫في العضل‬
‫كل صباح‬
‫عند الضرورة‬
‫يوميا‬
‫ مرات يوميا‬4
‫كل ساعة‬
‫كل يوم‬
‫كل مساء‬
‫حبة‬
‫تحميلة‬
‫احيانا‬
‫غرغرة‬
‫كل‬
‫محلول‬
‫كمية كافية‬
Light
large
‫خفيف‬
‫كبير‬
Chapter 4
Physical pharmaceutical procedures
33
Physical process:
It consists a group of primary operations, in order that the pharmacist
needs to prepare the pharmaceutical dosage form in its final shape, so
that the patient can use it easily to get its desired therapeutic effect, and
the pharmaceutical process are classified to:
1- Mechanical pharmaceutical process, it consists (includes):
a- Partitioning.
b- Separation (isolation).
2- Physical pharmaceutical process, it consists:
a- plain physical process.
b- Physical process which needs cooling or heating.
c- Physical process which needs solvents.
*The following is a detailed demonstration for the above classification
of pharmaceutical process:
1- Mechanical pharmaceutical process:
34
First: partitioning:
It is an essential primary pharmaceutical process, in order to prepare
pharmaceutical dosage form, and it is aimed to decrease the size of the
used medicament in order to be useful (been fitting from it)
pharmaceutically.
(1)- Portioning the solid, hard particles and it is done by the
following method:
A) Cutting:
This operation needs a force to cut the medicaments to smaller pieces,
and this is done by using sharp instruments, these instruments differ,
according to the hardness of the medicaments such as liquor ice root or
leaves of thyme and for such operations the following instruments are
used:
a- laboratory scissors.
b- Hand cutter.
c- Scissors with parallel blades.
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B) Impact:
This method is used in partitioning the hard and dried objects and we get
finer product form the one before, EX. Used in partitioning, gum
Arabic, dried leaves of peppermints, we need to conduct this operation
in closed vessel (container) because after using process of impact on the
drug dust will be produced as irrelative odors, as plant charcoal, for this
operation the following instruments are used:
a- wooden hammer or stone hammer or iron hammer.
b- Pestle and mortar, and it will be made of iron or porcelain or wood
and we should take care about the oxidizing metallic salts and not
impacting in an iron mortar, and also metallic salts and not impacted in
a glass mortar.
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c- The mortar with a hanging pestle is used for continuous operational
impact.
d- Hammer mill is used in pharmaceutical industry for its strength and
capability in production
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hummer mill
C) Attrition:
This operation following the impact operation or cutting operation and
is aimed to get a very fine powdered medicament and the following
methods are used:
1- Levigation:
Is called direct attrition and carried by using a hard tangable mortar and
hard tangable. Pestle in order not to slip the materials to the sides of the
mortar and after this operation is following is usually sifting procedure
to get the required degree of fine powder.
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Here the mortar should be covered during the process of levigation for
materials having smoke (dust), such as lead oxide and digitalis leaves
and generate explosion such as potassium chlorate.
2-Rrasping:
Rasping with friction is done by placing the substance on the surface of
the sieve and is gently applied friction and this will let the powdered
substance pass through the holes of the sieves, and the finesse of the
powder is controlled by the diameter of the holes in the sieves, which is
used for sifting, EX. Lead carbonate and magnesium carbonate.
39
3- Crushing:
Here oil containing substances are used, such as Aniseed and Coffee, for
this either mechanical or hand operated mills are used.
4- Trituration:
Mortar and pestle are used for soft fatty (greasy) substances.
D) Combined attrition and impact:
Here two types of mills are used:
40
(1st) Ball Mill:
Here the partials of the substance meet the balls where the powder is
attrited (change the powder) and impacted when coming in contact with
each other (the balls).
(2nd) The Fluid Energy Mill:
When attrition and impact operation are combined together, the process
carried through the fast moving particle by each other, the particles
which are needed to be changed to finer powder particles.
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2- Partitioning of liquids and viscous (sticky) materials:
Here homogenizers are used where the liquid is distributed like very
small droplets forms, EX. Partitioning the water in the oil by using
emulsifying agent.
And for the viscous (sticky) materials we use mechanical or manually
operated kneading machines.
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Second: separation:
Is divided into:
(1) Separation of solid substances from each other and this is
done by one of the two methods:
a- choice and purification is aimed to get red of the foreign
substances and impurities and unimportant part from the drug.
-And done by:
1- Manually (by hand):
Ex. Separation of plants leaves from its flowers or removal of
pebble and sand from the seeds of lentils.
2- by water:
As light objects float on water surface or dissolution of
dissolution of some substances with water, and it is precipitated
or removed (get rid of) some of the shells, such as almond with
water.
3- By air:
Here the light objects are removed (get rid of) when they are
exposed to air.
b- Sieving (sifting): depend on this separating operation by using
different sized of sieves to separate objects, according to the
dimensions of their parts.
(2) Separating solid objects from liquids and liquids from
other liquids and is done by one of the following methods:
a- By decantation.
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Used to separate solid objects from liquids, depending on their
heaviness of weight, then the liquid is separated from the surface
of the precipitate found in the bottom of the vessel.
b- By expression.
This method is used to separate the liquids from the solid objects.
Here we need pressure to expel the liquid found in between the
particles (molecular) of the solid object as in the case of fruit
expression.
c- By centrifugation.
This depends on the characteristic of central expulsion force, to
separate solid objects from liquids, and liquids from other liquids,
a clear example of this is by separating the components of the
blood (R.B.C) and(W.B.C) from plasma by centrifugation.
d- By filtration.
It is aimed to separate solid objects from liquids. And for
filtration we use:
1- Funnels and different types of filtration papers or cotton.
2- Cloth filters such as the ones used in preparation of cheese or
for preparation of syrups and liquid extracts.
3- Glass and porcelain funnels, ex. Buchner funnels, which
depends on evacuation of air and filtration of large quantities in
shorter times depending on that (the vacuum), and sinter glass
filters and Pyrex filters and filters consisting of cellulosic fiber
filters, and Millipore filter which is made of cellulose acetate of
different dimensions, where we can separate bacteria from liquids
and it is used in drug industry, because it can withstand heat and
we can use it for several times.
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e- Clarification.
It is a method of isolating solid objects form liquids and is done
by adding chemical substances to liquids where it works by
attracting impurity particles to facilitate filtration, EX. For such
substances are kaolin, and talc, silica gel(used as clarifying
substances), also water of Eau de colon is clarified by using
magnesium.
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2- Physical pharmaceutical process and consists:
First: plain (pure) physical process and it means the physical
properties.
viscosity
It is defined, by the internal resistance or friction which is
produced in a liquid, resulting from the movements of the layers
of the adjacent liquid in relation to each other.
And it is a characteristic of liquids only.
Factors affecting viscosity:
1-Degree of temperature:
The relation is inversely between the viscosity and temperature
degree. Hence when there is an increase in the temperature
degrees, viscosity is decreased, that is because the increase of
temperature heats in the matter and heat is stored as energy and is
used as kinetic energy, by this energy it will overcome the
resistance present in between the molecules of the liquid.
2- The chemical bonds found in the matter:
As the force of attraction is increased between the layers of the
liquid, the viscosity is increased.
How do we measure viscosity?
Viscosity is measured by several instruments among them is the
viscometer, with a unite of measurement called (poise) its symbol
is (&) = Theta.
(&) Theta=g.cm (-1) sec (-1).
46
viscometer
There is an easy method to measure the viscosity by an
instrument which is called (the falling ball) and the principle
which this instrument depends upon this is:
Get the unknown viscose liquid and put it in a graduated vessel
(here we may use burette) in a standing upright perpendicular
position to the earth, and then we get a metallic ball of known
weight.
Then we drop the ball from the above into the vessel (here the
burette) in a free falling and when it (the ball) touches the surface
of the viscose liquid we start measuring the time in seconds (by
47
stop watch) and calculate the time it will take to reach to the
bottom of the vessel and the high of the viscose liquid is
measured by centimeters (cm) and by using the given formula
above we can calculate the viscosity of the unknown liquid.
&=g.cm (-1).sec (-1).
Why do we measure the viscosity?
We benefit from it in the process of the pouring of the liquids of
pharmaceutical dosage form.
The boiling point:
Boiling point is defined: which is the degree of temperature where
the vapor pressure of the liquid is equal to the atmospheric air
pressure.
Or it's also defined: it is that degree of temperature where the heat
kinetic (the kinetic energy) is capable in over coming the force of
the attraction found among the molecules of the liquid.
How do we measure degrees of boiling point?
We bring a vessel and fill in it some (or specified) volume of a
certain liquid (where its boiling point is to be determined) and dip
in the liquid a thermometer, and then we draw a curve between
the time and the temperature. We will find as the time goes by
(increase), the temperature degrees are increased until we will
reach to a certain point which the temperature degrees will stop
from increasing, although the time is passing by and this
temperature is the latent heat, the heat given to the liquid phase
and is consumed as an energy to change the liquid phase into
gaseous phase.
For that reason the temperature degree stopped (stayed constant)
then the temperature degrees will return back to be increased
48
again, because it will store the heat to utilize and benefit from it in
the process of breaking the bonds.
*Factor which affect the boiling point:
(1) - The pressure:
Is directly proportional between the pressure and the boiling
point.
As much as the external pressure is increased as much as the
boiling point is increased and the opposite is correct.
(As the external pressure is decreased the boiling point is
decreased).
Ex. When we want to boil an egg on top of a mountain and an
another egg at the sea level surface, we will find the egg on the
top of the mountain will boil faster than that at the sea level, that
is because the boiling point at the external pressure of the sea
level will be more and will take more longer time.
Example:
Atmospheric pressure
760 mm Hg
700 mm Hg
17 mm Hg
Boiling point in water
100c°
97.7c°
20c°
We will find the relation is directly proportional, the atmospheric
pressure and the boiling point, meaning" if the boiling point is
increased then atmospheric pressure is increased ".
(2)- Force of the attraction and the kind of the chemical bonds
formed to the matter.
Example:
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Diethyl ether[CH3CH2OCH2CH3]
Ethyl alcohol[CH3CH2OH]
Water [H2O]
Boiling point is 39.6c°.
Boiling Point is 78.8c°.
Boiling Point is 100c°.
- The forces between (diethyl ether) are the Vander vale and it is a
very weak force, so that it will break up easily.
- For (ethyl alcohol) some of it is Vander vale forces and the
remaining parts are hydrogen bond, for this reason the boiling
point of ethyl alcohol is more than the diethyl ether.
- For the water the bonds are hydrogen bond, and it is very strong,
stronger than the Vander vale force, for that reason the boiling
point will be more than the both mentioned above.
Note: the boiling points of the polar compounds are higher in
their boiling points than the non-polar compounds; this is because
in the polar compounds there is the force of attraction and the
direction of these forces among the bonds, while in the non-polar
compounds there is no (resultant) and no direction and it could be
overcome on these forces easily.
We benefit from the boiling point these cases:
1- To preserve some of the pharmaceutical dosage forms, which
contain evaporation able substances in certain degrees of
temperature and in cold.
2- Aerosols: we choose different kinds of propellants so that at
the normal atmospheric pressure they will have low boiling
points.
3- Sterilization: the substances of low boiling points could not be
sterilized by heat because of their low boiling point, they will be
evaporated (volatilize).
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The melting point:
Is defined: it is that degree of temperature which the substance at
its solid state is transferred (changed) to a liquid by heating.
*Factors affecting the melting point:
1- Type of the chemical bonds in the compounds
as much as the chemical bonds are stronger as much higher will
be the melting point.
Ex. Water melting point is: 273k°.
Benzene melting point is: 278k°.
Then the melting point for water is more than that for benzene
because the chemical bonds found among the molecules of water
is very strong and these are hydrogen bonding, and for the
benzene molecules are weak because they are of Vander vale
forces.
2- Effect of temperature on the melting point:
We bring a vessel and put the solid substance in it, we put the
thermometer and we expose it to the heat and start drawing a
curve between time and temperature, and at a certain degree of
temperature it will stay constant (stops rising) and at this point the
solid substance will start to change (transform) from the solid
state to liquid state.
And at this point the heat is stored to be breaking the chemical
bonds among the molecules of the solid substance and the
temperature degree will stay constant until the whole solid is
transferred (change) to a liquid state completely, after this, the
temperature again will start to rise.
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This curve is called the curve of temperature effecting on the states of
matter (the latent energy for melting) and is defined: is the heat required
to transform (change) one gram of the solid state to a liquid state.
*We can measure the melting point by:
1- Capillary method (by using simple air eyes to watch the (M.P).
2- Using kofler block.
3- Using a microscope.
4- The bent tube method to measure the melting point of waxes
and fatty matter.
Freezing point:
Freezing point is equal to the melting point for the same
substance, but they differ from each other in that, the freezing
point loses the heat while melting point gains the heat.
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PH (hydrogen ion concentration):
It is hydrogen ion concentration.
PH= -Log [H].
And for the acidity (hydrogen ion concentration) it has special
importance for the drugs it:
1- Effects on the activity of the drugs.
2- Effects on the stability of the drugs.
3- Effects on the degree of the solubility.
We measure the degree of acidity by using ph-meter (digital or
analog).
Example (1):
What is the acidity (pH) of a solution of HCL, when its
concentration is equal to 0.05%?
Note: the unit for hydrogen concentration is (mole/liter), m.wt-for
HCL=36.5?
Example (2):
What is the hydrogen ion concentration for a solution the pH = 2?
The density:
Equals mass/volume = density = gm/ml (gram/milliliter).
It is measured by the following methods:
a- Banme method is to measure the density of liquor, milk and
syrups.
b- Gaylussac to measure the density of alcohol.
c- Westphal method for all the liquids.
Measurement of degree of hardness:
53
It is the characteristics (properties) of viscose pharmaceutical
dosage forms such as suppositories, ovules and it is done by using
instruments for measuring the degree of hardness.
It is used to know the suitable (proper) conditions to store and
preserve such pharmaceutical preparation.
Measuring the degree of turning of the polarized light to the
left or right by using a polar meter.
Measuring the degree of light bending (refracting) by using a
refract meter.
Chromatography:
Is done by different methods, using paper chromatography, this
layer chromatography or by column chromatography.
By electrophoresis.
Measurement of friability:
Used to check (measure) the hard type pharmaceutical dosage
forms specially the tablets.
Degree of hardness
Disintegration:
We will study the above-mentioned methods of analysis in the
coming chapters.
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Second: - physical process which needs cooling or heating:
1) Evaporation:
- It is a process of removing (eliminating) of the liquid from a
solution by evaporation to get a concentrated liquid, thick and
most of the times the liquid which is evaporated is water or
alcohol or ether.
- The evaporation process is a primary process to the drying
process.
- The evaporating process needs heat to be completed.
* Aims (goals) of evaporating process:
1- To get a thick liquid as in the preparation of liquid extracts or
soft extracts.
2- To get a super saturated liquid as in the process of
crystallization.
3- To extract the active ingredients from the plant sources as in
the medicinal plants containing volatile oils.
* Factor which effect in the process evaporation:
1- Temperature degrees.
The amount of heat given to the process of evaporation should be
equal to latent energy needed for evaporation.
2- The pressure.
Hence increases the capabilities of evaporation.
And this is important for the substances which are damaged when
they are exposed to high temperature for long period of time, as in
the cases of vitamins, hormones, and antibiotics.
55
3- Type of the substances.
Some of the substances are affected by heat and moisture, which
is (heat and moisture), produced during the process of
evaporation, this problem is solved by decreasing the pressure.
4- The surface area exposed to evaporation.
As much as the surface area is larger (greater) the process of
evaporation will be faster.
5- Concentration.
As the solution is more concentrated the process of evaporation
will be less because:
a- It needs more heat to break the chemical bonds among the
molecules.
b- Because the concentrated solution or viscose(sticky) solution
retard the transference of heat from the bottom to above(top) and
then it will retard the evaporation process.
*The instruments used in the evaporation in the industries
(firms) are called (evaporator) there are three types of them:
1- Pan evaporator.
It is consisting of a vessel, its thickness is very little (fine) and
inside it the liquid is poured (putin) which is to be evaporated,
and from the bottom it is exposed to heat and from the above
(top) it is opened.
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*Its properties
a- Easy to use.
b- Cheap.
c- Simple and available.
d- Could be manufactured and it is easily cleaned.
* Its problems:
a- Its heat transference is not good and non-homogenous.
b- Probabilities of appearance of precipitants in the bottom of the
vessel are possible and this is because of its bad thermal
transference.
2- Cold film evaporator.
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This instrument is different from the previous one in that it is
connected to a tube which is put it from the above and it is cold,
and it the emitted vapor is collected and condensed, and then its
exposition to heat is decreased, but parts of the liquid is not
exposed.
3- Rot vapor.
It is consisting of a rounded flask in water bath, attached to
vacuum pump and a condenser.
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Its benefits advantages:
a-The source of heat is constant because it is from water bath.
b- During the evacuation the whole liquid is exposed to heat.
c- The air which is produced is collected through a vacuum pump
and then the pressure is decreased, (pressure = zero).
d- The vapor is collected and condensed in a condenser.
And for the evaporation in small scale we use what is called
(bath) and it is consisting of several types and the most important
ones are:
1- Water bath.
Used for substances (liquids) to evaporate while their boiling
points do not exceed more than 100°c and this method is used for
the substances which are affected by direct heat.
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2- Sand bath.
Here we use a layer of sand instead of water and is used to
evaporate the substances which their boiling points are greater
than 100c°.
3- Oil bath.
Here some amount of oil is used instead of water or sand to get
temperature degrees more than 300°c and there are different kinds
as the oil types used are different.
4- Saturated solution bath.
Here we use saturated solution with some salts, as solution of
potassium nitrate, where its boiling point reaches 115.2c° or
calcium chloride where its boiling point of saturated solution
reaches to 179.5c°.
* Desiccation:
This is a process where the water is separated from the solid
objects (substances) or gaseous or liquids and this is done by the
following methods:
a- Evaporation (direct heating).
b- Using solid substances which absorb the moisture, as silica or
calcium chloride.
c- The effect of the lowered pressure.
d- By expression (squeezing) mostly for some parts of the plant or
the fibers which contain the liquid.
e- Extraction by using another liquid (liquid separation).
Example of extraction:
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There is a substances which is dissolved in a liquid (ex. water),
what do we want to do is to separate the soluble substance which
is already is dissolved in water.
So we will place it in an instrument (separators funnel) and then
we add to it a volatile liquid to the water (it should be nonmiscible with water) this substances now will be dissolved more
effectively in the volatile liquid (ex. Ether), we will notice that
this substance is solublizes now in this ether and will leave the
water layer and we will separate this immiscible liquid from the
water, then we will evaporate this volatile liquid by exposing it to
the air in the hood.
What will remain behind alone are the substances which were
dissolved in ether.
f- Some gases could be separated from the water and other liquids
by passing it in a column containing sulphuric acid where the
gases will be reacted chemically with the acid and water is left
without gases.
*But the problem is that the taste of sulphuric acid will be evident
in it (gases).
Besides what have been mentioned there are other means of
dissection and there are:
a- Natural drying method.
By direct exposing the plant sun or placing it in the shade and
to a stream of air for the substances which are sensitive to sun,
such as the plants which contain (volatile oil) so these plants
are dried in the shade.
b- Artificial drying method.
1- Using ovens for substances which can withstand heat so
they will pass through a stream of- hot air.
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2- Using desiccation (by cooling desiccation) this method is
suitable for the substances which are damaged by heat.
3- Using substances which absorb moisture such as silica and
CaCl2.
The aims (goals) for the desiccation:
1- Increasing the stability of substances because it is:
a- Water media is a good fertile medium for bacterial growth.
b- Good media to take place for chemical reaction.
c- Enzymes which by degradation some substance so this
activity will be decreased by the absence of water.
2- To get solid substances from a group of other substances (a
mixture).
3- The dried substances will occupy lesser area and this is
important in storing and during shipments, it will cost less and
this is beneficiary in the process of importation.
4- It will make it easier in several pharmaceutical processes
such as milling and mixing.
5- Improve some of its physical properties from some
substances such as solubilization and pouring and flowing.
*Process desiccation:
The expression" dry" denotes that the substance is dry but
contains a certain proportion of moisture, and it will be in
equilibrium with the percentage of air moisture contain in a
certain temperature degree in a certain atmospheric pressure.
Example:
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It was found at a (20c°) degree of centigrade and at one
atmospheric pressure.
The air moisture content is (70-75%) this means that the
percentage of air moisture does not equal always (70-75%) for
all the substances.
Also the starch at (20c°) temperature at (1 atm) pressure, the
air content of moisture is (15%) and this different for different
nature of substances and this will specify the moisture content.
If we try to draw a curve between the moisture content with
time on a graph paper for a certain substance we will find in
the beginning it will be leasing and to decrease in moisture
content and then we will find that nearly stability and the
region which will be stabilized is called: equilibrium moisture
content, and it is the moisture content at the equilibrium and is
defined:
The amount of moisture that is present in the substance in the
case of equilibrium with the air moisture at a certain
temperature and certain atmospheric pressure.
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At the beginning the dilution is the elimination (removing) of
water molecules is very fast until it will reach to a value of
equilibrium after that if we continue in the process of desiccation it
will need a longer time to lose the moisture with its exposure to a heat
source more, and this will accelerate its damage when it comes in
touch (contact) to the air moisture so it will return to gain moisture
equilibrium.
Note:
We should not dry the substances more than it is needed because
every substance has its specific degree of desiccation.
*Factors that specify the moisture content at equilibrium
"factor effecting the desiccation":
1- The atmospheric pressure.
2- Temperature.
3- Type of the substance.
4- Atmospheric moisture content.
The substance which has a certain percentage of moisture differs
according to the difference of pressure and temperature and moisture
content.
Ex. Starch has moisture content (10-15%) at a certain temperature and
pressure.
Note:
EMC (equilibrium moisture content) differs from one substance to
other and also differs for the same substance so it depends on the
pressure, temperature and content of the substance.
* Dryers:
It means the instruments used for drying; we can classify the instruments
used for drying by several methods:
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1- According to the process of heat transference inside the machine is it
by conduction or radiation or by convection and this is classification is
followed by the companies.
2- According to the position of the substance in the machine, it is static
(non-movable) or movable.
3- According to the pharmaceutical dosage form of the substance, which
is wanted to be dried, is it solution or suspension, or solid substance and
this classification are followed in the pharmacy science.
a) Drum dryer.
The circular disc (drum) dryer is used for the solution and dilute
suspension.
* Its principle: the drum dryer consists of circular steel disc (drum) of
(0.75-1.5 meters) in diameter and (2-4 meters) in length.
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And is connected in a way to a heat source, mostly electrical and is
placed in a feeding pan, containing the solution or the diluted suspension
and in which the drum rotates, the liquid is applied to the surface and it
sticks to it because it is hot and spreads to a film which dries rapidly.
The dried product is scrapped from the surface of the drum by means of
a doctor knife in the form of flakes collect into another basin.
The drying rate can be controlled by adjusting rotation speed and
temperature of the drum.
But the problems are:
1- The heat transference is not uniform.
2- Source of heat is direct and hence the substances which are damaged
by heat we cannot use this machine.
Substances which can be dried by this method include milk products,
starch product, iron salts and suspension of kaolin or zinc oxide…..etc.
b) Spray dryer
It is a sprayer consisting of a valve containing a heating machine to heat
the air and there is also a place for entering of hot air in a horizontal
position and the instrument (which contain the substances) the atomizer
ejects in a form of spry containing the substances to be dried, and when
the hot air meats this spry it will dry the substance and this heat(energy)
takes the sprays moisture evaporates and the hot air will come down to
the bottom of the drying chamber in a circular (cyclone) way and from
the other end air will get out, and the air before leaving the machine it
will pass through a filter paper which will separate the dried solid
particles from the air.
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Which of them is better the spray dryer or the drum dryer?
1- Heat distribution is better.
2- There is no direct contact with the substance.
3- Size of the particles is uniformly about the same size.
4- Shape of the particles is in a spherical shape and better, where its
solubility is increased and better in flowing properties.
c) Try dryer (shelf).
The tray is an oven consisting of different trays layed down in layers and
the substance to be dried are placed on the trays (shelves) and the source
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of the heat is different, either from the bottom or from the top or from
the sides and the substance will remain constant in its place, the heat will
travel from the bottom to the top.
- Disadvantages:
1- The place where the substance is layed down is non-changeable.
2- Heat transference is bad.
3- We will not get the substances in a spherical shape but in the shape
which was placed down on the trays.
*This method is used for the solid substances as powder and semi solid
substances as pasts.
d) Fluidized bed dryer.
It is dryer for solids and semi solid substances are placed in it, where the
air is being heated and entered the machine through very narrow opening
in the bottom, hence the substances are forced by pressure and all are
directed to the bottom of the basin, and this bottom is consisting of a
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sieve, and the substance which is going to be dried should be
moisturized so the moisturized substance is bombarded (bumped) with
hot air (containing a great amount of kinetic energy) and this hot air will
raise the particles to the top and will break it and will give an energy to
the substance, where the substance will move to the top and will bump to
the filters found in the above which will pick up the tiny particles of the
substance.
Note:
The movement of the particles is resulted because of the air and not a
liquid for that reason it is called "fluidized".
Advantages:
1- Amount of the product is a large.
2- Shape of the particles is uniform and good.
3- Easy to operate and does not need to any effort.
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Disadvantages:
1- Amount of the powdered substance is mixed in a very tiny form
which will be attached to the machine and will pass in it.
2- Because of the friction static electrical charges will be produced on
the particles some times.
Lyophilization:
The substance which is to be dried should be a liquid or if it is solid it
should be dissolved.
This method of drying is used in the following cases:
1- For the substances which are destroyed by heat.
2- For the substances of low solubility.
3- In the case where the substance contains a rare active constituent.
Advantages:
1- No need to use high temperature.
2- Could be carried under sterile conditions.
3- Can get a uniform product which is very soluble in water.
Disadvantages:
1- Very expensive (high cost).
2- Capability of absorbing moisture is high so the products should be
kept in dry places and condition.
Ex. For substances kept and stored by lyophilization is (plasma
vaccines, meat).
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Distillation:
It is a process of separation where the condensed vapor which was
produced from vaporization of a substance and changing (converting)
it to liquid.
Aims (goals) of distillation:
a- Separation of liquids from each other or separation it from solid
substances (solid impurities).
b- Extraction some of the substances such as volatile oils from their
botanical sources as menthol.
c- Reusing (using again) the alcohol in a pure form.
d- Separating the volatile substances for other less volatile substances
depending on their boiling points.
* Types of distillation:
(a) Simple distillation:
Hence it is done in normal conditions and pharmaceutically used to
aim:
a- Purification and preparation of distilled water.
b- Re-purification of alcohol and separating the impurities from the
liquids.
Parts of the simple distillation apparatus:
It is composed of a heat source (flame) and two flasks, one of them is
to heat the mixture (No.1) and the second one is the receiver (No.2)
to collect the product, a condenser which passes through it a cold
water from a water source and which goes out heated (hot) because it
was exposed to hot vapor.
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The procedure:
The mixture is placed in flask (No.1) and gets heated, when it is
boiling water vapor which is hot is passed through the condenser,
where it is exposed to a cold surface, here the temperature is lowered,
then it will go from the condenser to the flask (No.2) in a cold
temperature, clear, free from impurities, some times to the flask
(No.1) is added few pieces of porcelain to regulate the boiling liquid.
(b) Fractional distillation:
This method is used to separate mixture of liquids differs one from
the other by their boiling points, and we use the previous instrument
1st evaporates the liquid with least boiling point, and is collected in
the receiver (flask No.2) then the flask (No.2) is taken away and we
use another flask instead of the prier one then we start collecting the
next liquid which has a higher boiling point then the 1st liquid and so
on.
This method is used to separate the component of the crude oil.
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(c) Distractive distillation:
This method is in the following cases:
a- To separate substances where their boiling points have high
temperature degree.
b- To separate substances which are destroyed during the general
distillation method.
c- To separate substances which are hard to be dispersed in water
such as volatile oils.
The plant material to be separated of its volatile oil in flask (No.2)
which exposed to water vapor which is generated from flask (No.1)
which is a separate flask, as it is show in the figure above, then the
water vapor is rising, taking with it the active constituents found in
the plant in flask (No.2) where it is exposed to the condenser which is
condensed in a form of liquid purified as shown in flask (No.3).
(d) Distillation under reduced pressure:
When decreases the vapor pressure of the liquid so in turn decreased
its boiling point, so it is used this method to separate the substances
which cannot withstand heat, then this method of distillation is used
for such kind of liquids which are effected by higher temperature
degree.
Fusion.
This is process of changing a substance (matter) from the solid state
to liquid state and it needs heat.
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Aims of the fusion:
a- Separation of solid objects from each other as impurities and is
done by fusing the matter which is needed and leaving the other one
in its solid state.
b- Mixing the medicinal matters with their solid solvents, during the
preparation of pharmaceutical dosage form as in the ointments, and
suppositories preparation.
c- Removing the water of the crystallization from the salts or matters
to preserve (keep) them as in calcium chloride (CaCl2).
d- Fusion helps in combing matters and formation of new
compounds.
Ex. Fe +S FeS
Sublimation.
It is the process of changing the matter from the solid state to the
gaseous state by heat without passing it to the liquid state,
And then these vapors are condensed by cooling, which we will
obtain the substance again in the solid state.
Sublimation is a distillation process for the solid objects, we will
benefit from it in the pharmaceutics (pharmacy) for the following
purposes:
1- Separating some volatile substances as it is the case in separation
of benzoic acid because it has the sublimation property.
2- Purification of some volatile matter as iodine, sulphur.
3- Crystallization of some volatile matter as mercury chloride
(HgCl2).
* Sublimation may occur at ordinary temperatures without heating,
specially the fast vaporization substances such as iodine, camphor
menthol.
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Crystallization.
It is defined as; it is process which aims to get (have) clean purified
crystals of the matter.
The aims (purpose):
1- To get a pure solid substance.
2- To improve some physical properties of the matter, as the
solubility, and the flow ability (pour ability) and mixing.
3- To get the substance in a certain form and a certain volume by
controlling the volume by method of easy mixing and fast cooling.
4- The crystallized substance is distinctive from the non-crystallized
by:
a- More stable.
b- Better shaped.
c- Better mixing.
Steps in obtaining crystals:
1- To obtain a solution super saturated and depends on the substance
by:
a- The evaporation.
b- Cooling.
c- Added chemical substance for the precipitation.
d- Changing the nucleolus degree of acidity (PH).
2-Forming nucleic (by scratching the glass or placing a thread or
glass balls.
3- Growth of the crystals is controlled by the fast mixing (shaking)
and cooling (difference of temperature degrees).
Types of crystallizers (instruments used for crystallization):
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1- Cooling crystallizer instrument, it depends on the difference in
temperatures degrees, where the instrument uses cooling process to
crystallizer it by cooling.
2- Crystallization instrument depending on evaporation, evaporating
crystallizer, or also crystallizer to obtain a saturated solution.
3- Vacuum crystallizer, an instrument for crystallizer uses air
vacuum.
The pressure here equal to zero and the temperature degrees are very
low and it depends on difference in temperature, its instrument
combines the two features (properties):
a- Evaporation.
b- Cooling.
Condensation.
Where the hot vapor is condensed during its exposure to cold surface
and step wisely is changed to a liquid and falls in a drop form, pure
devoid of impurities and this process is the major part in distillation.
Carbonization.
It is a process of changing the organic substance to carbon due to its
exposure to higher degree of heat as it is the case when sugar is burnt.
Cooling.
This process is aimed to:
a- Preserving the substances for longer time, ex. Insulin and vaccines.
b- Completing the distillation process as it is done in the part of the
condensation due to cooling.
c- Increasing the solubility of the substances fastally.
d- Extracting some of the substances such as the (yeasts).
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Chapter 5
Pharmaceutical procedures
which need solvents
77
Physical processes which needs solvents:
Consists of two processes the solution and extraction, the differences
in between the solution and the extraction:
Extraction
Solution
Extractions are a way to
Is the process of mixing solid
separate a
substances with liquids or liquids
desired substance when it is
with liquids or gases to get a
mixed with others.
uniform mixture the product is
The mixture is brought into
named (solution)
contact with a solvent in
which the substance of
interest is soluble, but the
other substances present are
insoluble.
*Both processes need solvent.
a) Solution.
This process is consisted of two parts.
One of them is called the solvent and the other one is called the
solute, and the products are classified by mixing the two parts
according to their nature as it is seen in the following table:
Nature of the Nature
solution
Pharmaceutical
solute
of the
dosage form
solvent
Solid
liquid
Complete
Solution
Solid
liquid
Partly(Suspension) Suspension
Liquid
liquid
Complete
Solution
Liquid
liquid
Partly(Emulsion)
Emulsion
Mucilaginous liquid
Partly
Mucilage
substances
Liquid
Gas
Partly
Aerosols
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* Steps of solubilization:
1- Dissociation of the solute (break up of solute-solute bond).
2- Transfer of the molecules of the solute among the spaces of the
solution and forms new bonds and may be hydrogen bonds or Vander
vale bonds, at the moment when the new bonds are stronger than
the bonds among the solvent alone and among the solute alone,
the substance (matter) is dissolved.
* But when the new bonds formed are weaker than the bonds among
the solvent alone and among the solute alone these new bond will
break up.
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* Types (kinds) of the solution:
1- Solutions are classified according to the nature of the solvent
and solute.
Solute
Solvent
Gas
Gas
Liquid
Solid
Gas
Liquid
Solid
Gas
Liquid
Solid
Gas
Gas
Liquid
Liquid
Liquid
Solid
Solid
Solid
Example
The air, O2 mixture of ether
and oxygen
Water with air or Br2 with Cl2
Vapor of I2 in air
Co2 in water
Alcohol in water
NaCl in water
H2 gas in Palladian
Mineral oil in paraffin
Mixture of gold and silver
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2- According to the nature of the solute:
a- Electronic solution.
These solutions are dissociated to ions or changed molecules and are
capable of delivering (passing) the electrical current and thus are:
1- Strong electronic solution.
2- Weak electronic solution.
b- Non-electronic solution.
These are solutions that consists of solute which is dissolved in a
form of molecules and are non-capable of delivering (passing) the
electrical current such as (sucrose in water).
3- According to the behavior and conduct of the solutions.
a- Ideal solutions: these solutions which do not show any change in
the characteristics of constituents (composition) when are mixed with
each other beside the dilution.
b- Non- ideal solutions (true solutions): these are solutions which the
characteristics and constituents (composition) are changed when
mixed with each other, ex. Giving off heat or gaining heat or decrease
or increase in the volume of the solution.
B) Solubility.
It is the number of the milliliters (ml) of the solvent which is capable
to dissolve (1 gm) of solute at temperature 20°c and at atmospheric
pressure of (1-atm).
And according to the definition of solubility we can classify the
solvent to:
1- Very soluble dissolves in less than (1ml).
2- Freely soluble dissolves between (1-10ml).
3- Soluble dissolves between (10-30ml).
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4- Sparingly soluble dissolves between (30-100ml).
5- Slightly soluble dissolves between (100-1000ml).
6- Very slightly soluble dissolves between (1000-10000ml).
7- Insoluble dissolves in more than (10000ml).
* Definition specific for titration or methods of expression for the
concentrations of the solutions:
Expression
Symbols
Definition
Molarity
M.C
Number of moles which
is dissolved in 1L
solution
Molality
M
Number of moles which
is dissolved in 1000g
solvent
Normality
N
Number of grams that is
equivalent of the solute
soluble in 1L solution
Mole fraction
X.N
Average of number of
moles soluble in
solution/sum of the
number of moles for
solute and solvent also
Percent by
% w/w
Weight of solute in
weight
grams in 100g of
solution
Percent by
% v/v
Volume of solute in
volume
milliliter in 100ml of
solution
Percent by weight
% w/v
Weight of solute in
in volume
grams in 100ml of
solution
Mole fraction
M.F
Number of moles of
one substance/number
of total moles=1
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Example:
We get three (3) substances number of moles of (A=10), and number
moles of (B=15), and number of moles of (C=25)?
1- 10+15+25=50
2- A= 10/50 =0.2
B=15/50=0.3
C= 25/50=0.5
3- 0.5+0.3+0.2=1
* Factor that degree of solubility depends upon:
1- Chemical composition:
The similarity in the chemical composition of both the solute and
solvent will help in the increase of the degree of solubility hence the
solubility of sucrose is increase in water due to the similarity in the
chemical composition of each other and also it is the same case for
the fatty matter and organic solvents, (like dissolves like).
2- Degree of acidity.
For each substance there is the optimum degree of acidity which
dissolves in (optimum pH), where the degree of acidity of the solvent
depends upon.
Ex. Alkaloids dissolves in acidic medium and does not dissolve in the
alkaline medium.
3- Degree of temperature.
Substances are divided into three parts according to their solubilities
with changes in temper degree:
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a- Substances where their solubility's are increased by increase in
temperature degree.
Ex. Sucrose.
b- Substances which are not affected their solubility's by increase or
decrease of temperature degrees.
Ex. Table salt (NaCl).
c- Substances where their solubility's are decreased by an increase in
temperature degree.
Ex. Calcium salts.
4- Combined solvents (co-solvency).
Where the solubility of some substances is increased when sharing
another solvent in addition to water the original solvent (co- solvent)
Ex. When preparing Gentian solution where we add alcohol to
dissolve Gentian violet, and then our original solvent (water) is added
to complete the required volume.
5- Forming complexes.
Where the solubility of some substances are increased when adding to
other substances which will chemically react with it and forming a
complex compound which is easily dissolved in the solvent (water),
when preparing iodine solution where (KI) potassium iodide is added
to form the complex compound as in the following equation.
KI+I2
KI3
* Factors that depends upon the rapid (quick) solubility:
1- Dimension of the substances (surface area contacted with solvent).
Where as much as the surface contact to the solvent is increased
between the solute and the solvent the (rate) (rapidity) of the
solubility is increased.
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2- Viscosity.
The solubility is decreased as the viscosity is increased.
3- Temperature degrees.
The increase in the temperature degrees will decrease the viscosity
and hence the rapidity of the solubility is increased.
4- Shaking and mixing.
Will increase the rapidity of solubility because the change of surface
contact between the solute and the solvent.
* Types of solvent used in pharmacy:
There are divided:
1- Either reaches to the patient (as it is considered a basic solvent in
pharmaceutical preparation).
2- Used only during pharmaceutical preparations.
* Conditions which must be available (present) in the first type:
a- Nontoxic and non-irritating.
b- Does not interfere with drug absorption process chemically inert.
*Conditions which must be present for the second type:
a- Not applicable for use.
b- Non-toxic to the worker preparing the drug.
c- Not expensive.
*Classification of the solvents according to the method of their
use:
1- Solvents used in the pharmaceutical industry.
a- Methyl alcohol. b- Ethyl alcohol.
c- Isopropyl alcohol.
d- Glycols.
e- Ethyl ether.
f- Chloroform.
g- Acetic acid.
h- Benzene.
i- Acetone.
2- Solvents used in the pharmaceutical dosage form.
Intended to be used internally:
a- Water.
B- Ethyl alcohol.
C- Glycerin.
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d- Propylene glycol (P.G)
e- liquid paraffin.
f- Olive oil and peanut and sesame oil.
3- Solvents used in the pharmaceutical dosage form.
Intended to be used externally:
a- Isopropyl alcohol.
b- Benzyl alcohol.
c- Butyl alcohol + ethyl alcohol + isopropyl alcohol.
4- Solvents used in Parentral.
a- water.
b- Ethyl oleate.
c- Sesame oil and olive oil.
d- Propylene glycol (P.G).
e- Ethyl alcohol and benzyl
alcohol.
Example of widespread used solvents:
1) Water:
Defect of water: good media for chemical and enzymatic reactions and
growth of bacteria, and the purified types are highly expensive.
Advantages of water: has no color and no odor, and easy to get it, less
coasty and chemically inert and is a good solvent for most of substances
and liquids.
2) Ethanol:
a- Solvent for alkaloids (the free type) and glycosides and resinous
substances.
b- Do not dissolve the gums, albumins and starch.
c- Most of the fixed oil are little soluble in it expect castor oil, it is
soluble in it.
- Important uses:
1- Antiseptic.
2- Co-solvent for drugs, ex. Gentian violet.
86
3- Cooling agent and rubefacient.
4- Used in liniments to facilitate the penetration of drugs in the skin.
3) Isopropyl alcohol.
- Boiling point degrees range from (80°c – 83°c).
- More toxic than ethyl alcohol, so it is not used in pharmaceutical
dosage forms, and not used internally so it is used for external
preparations, Ex. Lotion and cosmetics.
4) Glycerin.
It is considered as good solvents for the substances which are not
soluble in water, Ex. Phenol borax, but glycerin acts to dissolve gums,
starch and tannins.
Disadvantages (defects):
a- Preservative but less than ethyl alcohol by one half.
b- Moisturizing.
Uses in pharmacy:
a- laxative (mild).
b- Preservative.
c- Co-solvent.
d- Moisturizing (humectants).
e- Emollient.
f- Has a suspending activity (in pharmaceutical preparation).
- And differentiated from water it is sweet in taste viscous and derived
from carbohydrates.
5) Glycols.
Chemical properties are in between alcohols and glycerin.
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Uses: it is considered a toxic substance so it is not taken internally
expect (propylene glycols), and is used in externally preparation
especially in cosmetics.
Properties:
a- Absorbs water (moisture).
b- Water soluble.
c- Toxic.
d- Good solvent for gums and resinous substances and volatile oils.
Example of glycols:
a- (P.G) poly ethylene glycol.
b- Ethylene glycol.
c- Carbitol.
d- Diethylene glycol.
e- Propylene glycol (P.G) its chemical structure:
- Properties:
a- looks like glycerin in its physical properties but it is less viscous.
b- Missbile with water, alcohol, chloroforms and is not missbile with
fixed oil and light petroleum ether.
c- Preservative and could be used as a substitute for glycerin.
Propylene glycol (P.G) is more toxic than glycerin and (P.G) has the
ability as a preservative as the alcohol but glycerin has the half ability as
a preservative as alcohol.
d- Some of the drugs are stable in it as chlorophenicol, vit D,
progesterone, phenobariton, meaning we can use (P.G) as a solvent for
the above mentioned drugs.
88
But penicillin is not stable in (P.G).
6) Polyethylene glycol.
Are named by so many synonyms as macro gel, PEG, carbowax and is
used in the bases of suppositories.
The chemical composition, is a mixture of condensed of polymers
composed of ethylene oxide with water and its empirical formula is, n=
represents the number of the average molecular weight and it ranges
from (14-15) among the liquids, when, n= (15-50) nearly about, among
the solids and semisolids.
And we can get semisolid compound substances by mixing different
number of (n).
- Characteristics:
a- Missbile with water, alcohol, acetone and chloroforms.
b- Absorbs water and dissolves in it, easily missbile with liquids and
easily spreaded on the skin and easily removed.
c- Non-toxic, not irritant to the skin except in cases of skin
inflammation.
d- The ability to soluble; so many substances, Ex. Hydrocortisone,
salicylic acid, sulphur.
e- Stability during storage and very little incompatibility because it is an
inert substance.
f- Non-volatile.
g- Ability to form a demulcent base.
- Uses:
1- A bases for water soluble suppositories.
2- A bases for washable ointments.
7) Diethyl Ether:
Properties:
a- Volatile clear liquid.
89
b- Boiling point 34c°.
c- Inflammable.
d- Sweet taste and pungent.
e- Good solvent for oils (fixed oil) fats, alkaloids.
f- Less denser than water and also it is non-missbile with water.
- Uses:
1- It was used as inhalation anesthetic, but now days very little used in
this area because of the presence of better drugs and with less side
effect.
2- Pharmaceutically used in the preparation of collodions and it is not
used (the ether) externally made preparation because it is volatile and
also not used internally because it is irritant.
3- Used in the primary stages of extraction.
8) Chloroform.
It is a clear volatile liquid, has a characteristic odor, its boiling point is
(61c°) and its taste is sweet pungent.
And it is a good solvent for alkaloids and fats and it is preservative, and
it is denser than the water and not does not mix with it.
- Uses:
1- In the process of extraction.
It was used as inhalation anesthetic but nowadays not used for this
purpose.
Due to its high toxicity to the liver, kidneys and the brain, because it is
oxidized in the body to a toxic substance called (phosgene).
- Pharmaceutical preparation:
Ordinary (2.5ml/100ml).
D.S (double strength) (5ml/1000ml).
The water should be boiled to expel the oxygen which was dissolved in
water because oxygen changes to toxic substance (phosgene).
90
9) Acetic acid.
Glacial acetic acid means, concentrated acid.
The ordinary acetic acid it is a clear liquid volatile has a distinctive odor
and tastes acidic.
* Most of the times is used in the primary stages of extraction and is not
used as a solvent because it will react with other because it is an acid
and it is not inert.
10) Acetone.
Is a clear volatile liquid has a distinctive odor and used in the primary
steps of extraction to dissolve fats and resinous substances and enters in
the composition of paints and polish removers (eliminators).
11) Light petroleum.
Organic solvent consisting in a mixture of substances the most
important one is Hexane.
- Properties:
Very volatile and inflammable and does not mix with water.
- Uses:
Solvent for oils and fats but it does not dissolve the alkaloids.
12) Ethyl Oleate.
It is an ester produced by the reaction of the alcohol (Ethyl alcohol) with
Oleic acid.
- Uses:
Good solvent for the hormones and steroids and used efficiently as a
solvent for intramuscular injection, because it is less viscous than the
oils and easier to inject.
91
Its distention from the fixed oils.
1- It is does not congeal at lower temperature degrees.
2- Its injection is easier.
3- Absorption is easier.
4- The needle is easily cleaned from its traces (remains), and the
syringes.
13) Isopropyl Myristate.
It is also an ester produced by the reactions of isopropyl alcohol with
myrestic acid (14 carbon atoms).
- Properties:
1- less oily than the vegetable fixed oils and mineral oils (ex. Paraffin
oil) and mostly used as a substitute for them in the preparing of creams
and cosmetics.
2- It does not rancid because all the chemical bonds are saturated.
3- It dissolves so many hydrocarbons and waxes and fats, for that reason
it is used in the creams so it will soluble them more efficiently.
Note:
It is not used in parental due to its high viscosity.
14) Liquid paraffin (mineral oil).
It is a mineral oil obtained from petrol derivatives it consists of
hydrocarbon chains and it is a clear liquid non-volatile has a distinctive
odor and has a viscosity higher than the water, so it does not mix with
water and is not used much, although it is used in the preparations of
creams and ointments as a fatty and oily bases and its function, in the
ointments, is to facilitate the missability and giving the softness to the
preparation, so it is not used alone, but in combination with other bases.
* It should not be used in spays (nasal)…..etc.
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Because paraffin precipitates in the alveoli of the lungs, leading to acute
pulmonary infections and then to decrease (lesser) the defense line in the
body.
Note:
Solvents for sprays are water while solvents for aerosols are gas.
B- Extraction:
Extraction: is a process of obtaining an active constituent or a crude
extract from a plant or animal or from their solid or liquid components,
by employing a suitable solvent as alcohol or ether or chloroforms….
etc.. depending on the nature of the substance which is wanted to obtain
it.
* Factors depending upon to choose the suitable method of
extraction:
1- The nature of the substance, wanted to extract, where it is taken under
consideration its physical and chemical properties, such as its
solubility's, its degree of acidity(pH), capabilities of its volatilization
and its color and taste…….etc.
2- The preferred solvent and its availability, and achievement the
extraction goal by its employment.
3- The available, tools, (devices) and instruments in order to operate the
process of extraction.
4- The economic value of the substance wanted to obtain, by comparing
with the time and effort and the expenses for the extraction process.
* Factors depending upon in order to succeed the process of extraction:
1- The pre-treatment of the drug by sterilization or by removing the
impurities or by moistening, which will lead to obtain active
constituents, with good qualities and in a shorter time.
93
2- When temperature degrees are increased (in general) the rate of the
extraction is increased.
3- The presence of enzymes in the plant beside the active constituents,
accompanying, will hinder the process of extraction, so we should stop
(block) the action of these enzymes by heat or by precipitation, or
chemically to facilitate the process of extraction.
4- Mixing: will lead to increase the rate of extraction because it
increases the contact of the solvent with the surface of the drug.
5- The additive substances: will hinder the process of extraction or
changes the pH of the medium so it is preferred not to use them, only on
need, (when it is necessary).
6- The moisture content: This may lead to distinction of the wanted
substance to be distraction extracted, or getting substances with no
value.
7- Types (kind) of the solvent: hence, we should choose the solvent to
complete the process of extraction exactly, depending on the type of the
active ingredient, and the following conditions should be available:
1- Non-toxic if it was intended to be used internally.
2- Easy to remove by evaporation if it was intended to be used
externally.
3- Its boiling points should not be less than 30c or else it will be volatile.
4- Non-flammable.
5- With little viscosity which will facilitate the process of extraction.
6- Available and not expensive.
7- Will not cause to change in any of properties of active ingredient
(inert).
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* Methods of extraction:
1) Decoction.
This process is done by letting the drug to come in contact with the
liquid solvents and these solvents are in boiling temperature.
For a limit of time differs by different drugs to be extracted, where the
drugs is in divided portions are placed in a basin suitable for this
process.
With the required amount of the solvent (in most of the cease is water)
then it is heated slowly until boiling point, and heating is continued with
controlling on the temperature degrees for (15 minutes) in the cases
where the drug is in (a herbal form or flowers or leaves) and for (30
minutes) in the cases when the drug is in a form of (barks or root or
seeds).
After that the weight of the product is completed to the required weight
by adding boiling water, than it is filtered and the marc is expressed (is
squeezed) this process is applied usually to drugs that their active
constituents are not affected by heat of higher degrees(boiling), such as
extracting the (resinous products).
This method is not applied for the drugs containing volatile substances
such as essences and from another side, some of the substances are
dissolved by heat and then they will be precipitated by cooling and will
produce turbid solutions, such as the tannins.
* When using volatile solvents in the process of decoction we should
use puff up balloon supplied with condenser to avoid the lose of the
solvent using in this process (reflux condense).
2) Infusion.
This method is used in the drugs with thin tissues or in cases, which
contain active constituents that destroyed when, exposed to higher
temperature degrees of water for longer periods.
95
This process is applied by pouring boiling water on the divided portions
in a suitable manner which is placed in a basin which can stand with
heat with cover(lid), hence the basin is covered by the lid, and the
mixture is left inside for short period of time relatively this period may
reach to half an hour.
3) Digestion.
It is in between process by infusion and decoction hence the drug is
placed (which is wanted to be extracted its active constituents in a basin)
and added to it the solvent (most of the time is water) on a flame with
calm heat and left for a length of time longer than that we needed in the
process of infusion and shorter than we needed in the process of
decoction.
This method is used when active constituents is decomposed when
exposed to higher degrees of heat and also used to get the active
constituents from most parts of the plant.
4) Maceration.
We subject the crude drug to process of cutting and grinding and
changing to coarse powder or pieces then we place it in a basin with a
suitable size, we add to it solvent which will dissolve the substance
wanted (needed) to be isolated and we close the lid of the basin firmly
inorder not to evaporate the active constituent or the solvent.
And we leave it at room temperature for seven days, and to facilitate and
increases the rate of maceration, we shake the basin from time to time,
and we don't powder the drug in a fine powder, because it will make on
us harder during the process of clarification and purification.
* The addition and modification, which will help the process of
maceration:
1- Repeated maceration.
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2- Changing the solvents, Ex. For volatile oil of peppermint, (1st) we
macerate with water until the tissues are softened, we remove the
substances, which were dissolved in water, and then we macerate (2nd)
another time with alcohol.
3- Using heat.
5) Expression.
This is a process of mechanical pressure on parts of the drug, which is
juicy to obtain the juice, which contains the active constituents such as
expressing the lemon and oranges to get their juices.
6) Distillation.
Have been mentioned before in the process, which needs cooling and
heating.
7) Perculation.
This process is called the process of extraction by displacement and the
goal (aim, purpose) of this method is to extract greater number, which is
possible of active ingredient found with drug. By using the least amount
(least volume) of the solvent (or solvents).this process is carried out by
passing the liquid solvent slowly and uniformly (steadily) from above to
below (up to down) through powdered drug placed in a thick layer in a
perpendicularity form (position) in a basin called percolator.
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* How done this process?
Used for that a special instrument called percolator, which is in a conical
form, ends its narrow portion to bottom, facing the ground by a tube
equipped with a tap, and the size of the percolator differs according to
the amount of the powder to be percolated.
* Steps of the procedure:
1- The drug is cut to coarse or half fine (semi fine) powder, where the
drugs are levitated by caution in order to avoid any destruction may
appear on the active ingredients.
2- The powder drug is moistened with a suitable amount of the solvent
which is to be used, but not to form (make) a past, and most of the times
the powder is moistened with its half quantity of its weight with the
solvent, then the product is passed through a sieve containing wide
opening in order to remove any formed lumps.
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3- Then the mixture is set aside in a covered basin for (2-4) hours and
the powder is placed in the percolator perpendicularly, where the lower
part of it contains a small piece of cotton wool, and inorder to make the
substance of the powder to the solvent uniformly in all its parts, the
percolator is taped gently to its sides, then the surface of the powder is
strengthened, and covered by filter paper of circular shape or with a
circular metal with pores, or with washed sand or with pieces of broken
glass, then the tap is opened, here we will add the solvent on top of the
powdered drug until step by step, (gradually) the solvent will start
coming out of the tap, here the surface of the powder is covered by the
solvent of (2-3cm) above the powder, then the tap is closed and the
peculator is covered by a cover and let to maceration for a length of time
of several hours to several days, depending on the type of the drug and
strength of the solvent.
Then the tap(stop cock) is opened and the solvent stream(flow) is
arranged from the percolator in a slow drops with noticing (observing)
to keep the solvent on the surface of the powder in the percolator
constant (i.e. 2-3cm) so it should not dry out on the top.
And for this purpose the percolator is covered by an inverse vessel
looking like a funnel shape, and the rate of flow should be controlled in
order to get extracted solvent slowly containing a quantity of the active
constituents.
* Factors affecting the process of percolation:
1- The degree of powder fines.
The coarse powdered drug is hard to extract because of fast running of
the solvent through it, because of the presence of empty spaces among
the particles of the powder, which will not let the solvent for complete
extraction of the active constituents, and also the very fine powdered
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drug will not let among the particles of the powdered drug any spaces
for the solvent to pass through, and extract the active constituents.
So from the particle side view we will use powders with certain fines,
differs from one powder to another, and in the case of ipecac root the
powder is the half(semi) fine.
2- Moistening of the powder before placing in the percolator.
The purpose for that is to facilitate the percolation and it will make the
outer covers of the powder blown up(increases in size), which will help
the solvent to get inside the cells of the powder and then will facilitate
the extraction of the active constituent.
If the powder drug is placed in the percolator without moistening, the
enlargement of the powder (the cells) will hinder the passage of the
solvent among the particles and which will obstruct the percolators
percolation.
3- Maceration of the powder in the percolation before starting the
process of percolation (hours or days).
4- The rate of the flow of the solvent, as the rate of running is slower,
the extraction process is better.
5- The amount of the solvent to be extracted in general, it should be
continued in the percolation until exhaustion is completed from the
drug, and until the solvent coming out of the percolator is completely
free of the active constituents.
* And we can know that by the following methods:
a- Disappearance of the color of the liquid solvent coming out of the
percolator, for the colored powder.
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b- After evaporation to dryness, the extracted solvent coming out of the
percolator, leaving no residue.
c- The drug containing alkaloids could be tested by reagent specific for
alkaloids such as (Mayers), reagent will give a green precipitate, and
borherd reagent will give blackish red precipitate.
* Advantages of percolation:
1- Will extract great number of active constituent by little amount of
solvent.
2- The saturated solvent with medicinal drugs will not dissolve another
substance during its passage through the powder.
3- In the process of percolation there is no chance to loose any quantity
of the active constituent.
4- The renewing always with fresh solvents will help to extract
completely the active constituents presents in the drug and will renew its
ability for saturation.
* Steps in extracting oils and fats:
First: the fixed oils are extracted by:
1- Expression.
2- Percolation and maceration.
To expression may be:
a- Cold expression.
b- Hot expression.
There is an important note we should take it under consideration that is
to consider on what is left behind after expression.
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* Steps of expression process:
1- Pretreatment of the seeds before expression:
a- Removal of impurities.
b- Removal of seed coats scales from pistachio or peanut or removal of
hairs as in cotton seed.
c- Milling (grinding) the seeds or transforming it to paste or cutting it to
larger places.
2- We use in the process of expression electrical expresser, or by using
an ordinary expresser.
* Cold expressions: this method is used to preserve the nature
(character) of the oil.
Ex. Castor oil or olive oil in order to preserve the color, the taste, and
the odor.
* Hot expression:
- Advantages:
a- Faster and more completely done then the cold expression.
b- Before expression the drug is boiled with water, which will
precipitate the proteins and explode or break the cellular walls, which
may increase the rate of the process of expression.
- Disadvantages:
1- Due to storing the moistened seeds may lead to fermentation and this
process of fermentation with boiling (heating) will cause an increase of
the percentage of free fatty acids, and then will increase the problem of
rancidity.
2- Change of color and odor, the result of the presence of high
percentages of aldehydes and ketones and coloring agents which will
increase their solubility's in the oil at higher degrees of temperature
change of the color and odor).
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3- Stability (of the fixed oil) is decreased because of rancidity.
* Kinds (types) of solvents used in the extraction of fixed oils:
1- Pentane:
It consists a chain of five carbonate, one of its disadvantages is its low
boiling point and it is a gas (volatile) at the ordinary temperature.
2- Hexane:
It is better than pentane because it is cheaper and is available and its
boiling point is more than pentane.
3- Heptanes:
Its (B.P) is more than the first and the second one, we use it in cases
when extracting at higher boiling points.
4- Trichloro ethylene:
Characters: stable and non-volatile.
Disadvantages: hard to remove from solid substances in addition it is a
toxic.
5- Benzene:
Is an example of aromatic hydrocarbons.
* General principle:
These solvents are not used much and the reason is that these will
change the color of the fixed oils to darker color in addition these are
toxic and irritant.
6- Water missbile solvents:
Example (glycerin, propylene glycol), these have a disadvantage (its
activity) is decreased in the presence of water.
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Second: purification of the fixed oils.
And it is the process of the removal of impurities and it is done by the
following methods:
a- Filtration.
b- Centrifugation-central removal.
c- By hand (manually) removal of larger impurities.
Third: Refining oils.
It will improve the properties of the fixed oils. Such as the color, taste
and odor and stability.
* What are the impurities (pollutions) of the fixed oils?
1- The free fatty acids:
It will affect the stability and color of the oil, the typical method is to
remove them and it is done by natural and chemical equalization and we
use carbonates and bicarbonates of sodium (Na2Co3 and NaHCO3)
because these are weak bases and we do not use strong alkalis in order
at time of clarification will not make froth.
2- Phosphatide:
It will effect on the taste of the oils and we remove it by moistening.
3- Pigments:
These will effect on the color of the oil and we can remove them by
adding absorbing substances, which will absorb the pigments on their
surface as, activated charcoal and talc powder.
4- Substances causing odors:
We can get rid of them by distillation or by evaporation.
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* Extracting the volatile oils.
1- By distillation:
It is done by different methods, and the most important is:
a- Aqueous distillation: have we use plants that are not affected by heat.
b- Aqueous and vapor distillation: used for plants whether dry or fresh,
ex. cinnamon.
c- Direct vapor distillation: have we used this method when the plant is
fresh, ex. Peppermint.
2- By expression:
Here we use this method when the plant is capable of fermentation
because of heat, so we use the cold expression method.
3- The usual extraction:
Percolation or distillation.
For the extraction, we use the following solvents (Benzene and ether).
* Extraction of fats (Rendering).
How do we extract the fats?
1- By freeing the fat from the tissues by heating (in a free of air media)
or by using the vapor or an alkaline substance.
2- After the fat has been melted it is removed by cooling and then by
filtration.
Ex. Cod liver oil.
* Extraction liquid from liquid.
- The basic (essential) purpose:
1- Purification of the solid substance, ex. The antibiotic is (bacitracin),
from the liquid growth media, which the antibiotic is present in it, we
will add to it the solvent (Butanol), and then we add a precipitating
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agent to precipitate the antibiotic (Bacitracin) followed by its filtering
the perception.
* Factors depended upon for extraction:
- Liquid from liquid.
1- Distribution coefficient.
The substance to be extracted should have a distribution coefficient in
one direction toward one of the two solvent.
2- Surface tension.
Whenever the surface tension is larger between the two solvent then the
possibility of the substance to be transferred from one surface to another
is decreased.
3- Presence of impurities.
Will decrease the possibility of extraction.
4- Hydrogen ion.
Concentration-pH – the degree of acidity, ex. Alkaloid.
* How does the process of extraction is done?
The most important mechanism for the process of extraction is the
distribution, and is done from the region of higher concentration of the
substance to the least concentration region.
The ficks law for distribution average distribution = dm/dt.
The negative sign, indicator that the concentration in it has become over
the direction of the least concentration, meaning that the distribution is
carried from the region of higher concentration to the region of less
concentration.
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Chapter 6
Biopharmaceutics And
pharmacokinetics
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Biopharmaceutics.
Is the science that studies the relation among the sciences of physics,
chemistry, and biology and their applications on drugs or pharmaceutical
dosage form and effect on drug.
In order a drug to have its biological effect it should:
1- Be able to dissolve in the biological liquid.
2- Be able to move within this is fluid.
3- Be able to pass through the biological barriers.
4- Distributed to the wanted areas in the body.
5- Resist complexes of metabolism.
6- Be able to travel in enough concentration to the sites of their effect.
7- To have the wanted effect through the receptors or by other
mechanism.
The following figure represents the simple form for this chain of
complex events between drug administrations until to excretion.
The field that this relation is studied between the entrance of the drug
and absorption and distribution in the body and changes (metabolism)
and excretion the drug matter from the body is given the term
(pharmacokinetics).
* Bioavailability of drugs:
Bioavailability of drugs indicates the rate and extends of the drug
absorption; the rate of absorption is the rate that the drug is transferred
from the place of administration to the blood circulation system.
The indicators used to denote the rate of absorption is constant of
absorption (Ka) and time of maximum concentration and time of the
starting effect (T max).
1) Biological equivalence:
It is the term given on two pharmaceutical preparations for the same
drug matter and the same dosage, when they are almost equal in their
bioavailability (amount and time)
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Ex. If a person is given Panadol tab. 500mg.and after a time given
Revanin tab. 500mg. meaning of two different manufacturing firms, the
same drug but under different trade name.
We can say that the two drugs are bioequivalent when their
bioavailability look alike of the time and amount. Meaning if we draw a
graph of the concentration versis time for each of them and the largest of
absorption were close to each other at the same time.
Recent studies have proved that if given equal dosage of two drug
products containing the same active ingredient and of the same dosage
form for same patient, it is not necessary they have the same amount of
medicinal effect, and it was found also that the rate of drug efficiency
does not relate the active ingredients only but other factors as methods of
manufacturing of pharmaceutical preparation the excipients that it
contains molecular volume of active ingredients and other things.
2) Therapeutic equivalence:
It is the term given to two pharmaceutical preparations for the same
medicinal matter and of the same dosage so it is said they are
therapeutically equivalent if they give the same therapeutic results and
safety during its medicinal usage. The therapeutic equivalence is the
most important among the pharmaceutical equivalencies because the
goal of the using drugs is to get the best therapeutic results, which are
expected.
But because most of the time we can not measure the therapeutic effect
of the drugs, there is directly proportional activity between
bioavailability and therapeutic effect, so the measurement of the
bioavailability is considered one of the important support, that depends
the specific quality of medicinal products and its efficiency.
When we draw a graph of the log dose versis the response we find after a
while that the effect is constant because the response have been saturated
and if we increase the dose there will be a toxicity (toxic dose) and
through what have been mentioned we can specify therapeutic dosage.
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And the therapeutic equivalence may be changed because of addition of
excipients or during of manufacture, ex. During process of tablet
compression which may be different in two companies.
3) Chemical equivalence:
It is term given on two pharmaceutical preparations for the same drug
matter and at the same amount, when we apply on them the conditions of
physical and chemical analysis mentioned in the pharmacopoeia.
Ex. Phenobariton 50mg B.P, this sentences means that this drug has been
manufactured according to the British pharmacopoeia and this drug will
not enter the market unless we apply analysis which are found (mention)
in the pharmacopoeia and to be sure that they comply to the conditions
and those analysis has no relation with body, ex. Some analysis will
show the measurement of active ingredients found in the pharmaceutical
dosage form through solubility and absorption and these we have seen
that the term bioavailability is used to demonstrate the rate of absorption
of the drug from different pharmaceutical dosage form as it is
represented in the curve (concentration versis time) for given drug as in
the following:
And the data used in the bioavailability to specify:
1) Amount and percent of drug absorbed from a certain preparation.
2) The rate that the drug is absorbed.
3) The time that the drug stays in the tissue or biological liquid.
4) The relation between the amount of the drug found in the blood and
the therapeutic effect or the toxic effect.
* Factors used inorder to evaluate and compare the bioavailability:
1) Peak height concentration.
2) Peak time.
3) Area under the curve (A U C)(time_ blood concentration).
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* Pharmacokinetic.
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The reason of the usage of the drug in its pharmaceutical dosage form is
to have a certain therapeutic effect, so that we can specify the time of the
drugs effect the starting point, and drugs concentration in the body and
the time of its continuity (drugs activity).
So then starting the drugs usage, starts the process of absorption and the
drug reaches the required place where it will produce its effect through
bloods route, and most of the drugs are metabolized in the liver or the
spleen or the kidneys by different chemical process, such as oxidation
and reduction, splitting and removing of ammonia and combining with
enzymes…etc, and then the drug is excreted outside the body through
the kidneys or lungs or saliva…..etc.
It is known that the physical and chemical properties of the drug and
biological factors of the person using the drug have a great influence on
the therapeutic activity of the drugs.
So it is very important for each drug produced should be aware and be
acquainted on the procedures that happens on the body which are
absorption, distribution, and metabolism, and excretion, so the producer
would be able to produce a drug which keeps its concentration in the
body at the primary dosage (the starting dosage) and also the following
dosage on different suitable periods of time to have the required effect
with as little as possible of side effect.
Drug dosage and factors effecting upon it:
Drug dosage is defined that it is the sufficient amount to produce the best
therapeutic effect for a certain patient with the least dosage as possible,
and the amount of the drug which producer, generally, the required
effect for most of the patients, is considered the normal dosage for this
drug, and at the most it is the primary dosage for person receiving the
drug for the first time, and from that physician can increase or decrease
the following dosage, according to the need, for a drug to generate a
regular effect it should be absorbed and should be distributed in
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sufficient concentration to the receptor centers and to remain there for
sufficient period of time.
After specifying the concentration of the drug in the serum of the blood
on different periods (occasions), after administration it can be specified
the amount of the drug absorbed also it is possible to indicate the
average concentration of the drug in the serum of the blood which
represents the best concentration which gives the drugs effect upon the
patient, and this concentration is known as the minimum effective
* Absorption.
It is the process of transferring the drug from the place of administration
to the blood, were the absorption is concentrating on the solid
pharmaceutical dosage such as tablets, and capsules, where taken
through the mouth, where process of dissolving occurs then starts the
absorption process through the mucus membranes of the GIT and it
happens by the following ways:
a) Passive diffusion.
Where the molecules of the drug are transferred from the higher
concentration to the lower concentration, and it depends on the:
1- Size of the molecules.
2- Acidity of the medium.
3- Molecular penetration coefficient through the water_ oil barrier.
b) Active transport.
Where transferring the drug molecules by connecting with carrier which
does it transfers it to the other side of the membranes where it is left
there and so on.
And also transferring water soluble substances by protein or enzyme
carriers where the active transport process is done only in the upper part
of the small intestine, that is because of the enzymes and the carriers
their.
Example about substances absorbed by active transport:
1. Amino acids and drugs similar to it:
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a. L-dopa.
b. Methyldopa.
c. Tryptamin.
2. Salts of the iron and calcium and sodium.
3. Saccharids (sugars).
4. Some of the vitamins as (B12).
5. Pyramidines, which are nitrogenous bases like, halogenated
nitrogenous base used in the treatment of cancer.
c) Facilitated transport.
Mostly it needs a carrier and does not need for the presence of energy
and moves against the concentration, and example for the substances that
are absorbed by the facilitated transport:
1. Vit.B1 thiamin.
2. Vit.B2 riboflavin.
How diffusion is done through the lined barrier of the intestine.
The lining of the intestine is called (mucosa) and it is mucus membrane
and it is not continuous because of the presence of canals inside of it,
and it is noted that the drugs of low molecular weight with high
solubility in water mostly is absorbed through their canals found in this
membrane such as alcohol. While the drugs of higher molecular weights
and with some what higher solubility in oils are absorbed through
penetrating this membrane or by active and facilitated transports.
The low governing the absorption with passive diffusion is ficks first
law:
Dc/Dt= AD/h x C1-C2
Dc/Dt= average differences in concentration with times.
A= surface area available for absorption.
D= diffusion coefficient.
H= thickness of the diffusion layer wanted to penetrate it to arrived to
the blood.
C1- C2= difference in concentration between intestine and blood.
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As much as the surface area is increased and diffusion coefficient and
decrease the thickness of the layer wanted to penetrate to reach the blood
and increase the differences in concentration between the blood and
intestine it will increase the average differences in concentration with
time.
Distribution.
The blood starts the distribution after absorption process.
Factors that the absorption depends upon:
1. The physical and chemical properties of the drug, (molecular weight,
degree of ionization, distribution coefficient).
2. Blood supply to the tissue, as much the blood supply is large as much
the distribution is faster.
3. The combination with the proteins specially the (albumin) and this
effects the distribution of the drug.
Protein + drug
protein + drug complex.
This will be in complex form if the drug gets less in the blood stream for
any reason then the complex will compensate the decrease in the active
drug which is in a free state.
Goals or purposes of the binding drug with protein:
1. Transport of drugs is not soluble in water, such as steroid hormones,
and vitamins which soluble in oil.
2. Increase average of absorptions, specially the drugs that are ionizable
in the GIT.
The concentration of drugs in the blood stream is decreased when they
are bound to proteins, and then there would be a difference in the
concentration so it will be distributed it in faster way.
3. To get an even distribution of the drug inside the body.
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4. The free part of the drug is subjected (exposed) to the metabolism and
excretion, and for that reason the bound drug with the protein will
increase of its activity.
a) Methods of drug distribution.
It is the membrane of the blood capillaries- placenta and blood brain
barrier (B.B.B).
- Distribution of the drug through the membranes, and depends on:
1. The physical and chemical properties of the drug and its molecular
weight and its solubility in water and oils.
2. Blood supply.
3. The degree of acidity (pH): it is effect upon the alkaline and acidic
drugs.
a. Conditions of the drug which passes through the blood capillaries:
1- It should be water soluble and oil soluble, if it was completely oil
soluble it will be stored, and if it was ionizable it will not stored.
2- Molecular weight less than 500-600.
b. Distribution of the drug through the placenta:
Morphine- heroin, ethanol-nicotine, barbiturate, sulfonamides.
c. The drug that passes through the B.B.B should be oil soluble.
b) Distribution of the drug through the tissue is depended upon:
1) The physical and chemical properties of the drug: some of the drugs
are bounded irreversibly to the protein tissue such as (D.D.T), which is
bounded to the protein, and Tetracycline is bound to the bones.
2) Blood supply: as much as the blood supply is increased the
concentration of the drug is increased, in larger amount.
Some of the drug will get redistributed and its mean that the drug has
been distributed in the tissue it will reach to the blood stream, then it will
be distributed to other tissue. Then it will affect after 30 seconds (1/2
minute) because it reaches to the CNS as in (Thiopental Na) and it will
end after (1/2 hour) (30 minutes) because it will be concentrated in an
oily tissue because the drug of lipophillic type loves the oil.
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Excretion.
Consists of two processes the Excretion and Metabolism.
First: The Excretion.
This is process it's done through:
1) The urinary system (kidneys): it is the major organ to excrete, and
inside it occurs:
a. Filtration of the drugs by the kidneys it depends on the molecular
weight.
b. Reabsorption of the through the urinary tubules to the blood, which
depends on properties of the drug and the acidity of the urine.
c. The secretion which is carried from the blood to the urinary tubules
and it's an active transport.
Drugs of active secretion are (Salicylates, Furosemide, Indomethacin,
Thiazide, Quinine, Penicillin, and Dopamine).
2) Through the Gall Bladder:
It is carried through the interohepatic circulation.
Factors that depends upon the excretion through the gall bladder:
a. Molecular weight of the drug: and it is conditionals that the molecular
weight should be very high.
b. The chemical composition of the drug and its polarity.
c. Gender (sex) effect of secretion of the gall bladder.
Some of the drugs that excreted through gall bladder (Rifampicin,
Clomiphen, Clomid, Stilbesterol).
There are some of the drugs, which are stored in the gall bladder, and
then the activity of these drugs is prolonged.
3) Excretion through the lungs: here in this route is excreted the volatile
matters and gases, such as (Ethanol and Paraldehyde).
4) Excretion through the saliva: ex. Phenytoin, sulfonamides,
Phenobarbitone, Tolbutamide, Theophylline, Rifampicin.
And these drugs may have side effects in the tongue, like the metallic
taste, and this method is used to measure the concentration of the drugs.
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The drug, which is excreted through the saliva, may return to the
intestine then the saliva again meaning the drug is having an oral saliva
circulation.
The excretion of the saliva depends on:
a. Degree of avidity.
b. Distribution coefficient of the drug.
5) Excretion through the milk: for example, (Alcohol, Tetracycline).
Factors that depend the excretion of drugs through milk:
a. Degree of acidity.
b. Molecular weight intermediate too small.
c. Degree of solubility of the drug in fat.
6) Excretion through the skin: the drugs that are excreted through the
sweat, Ex. I2, Br2, Benzoic acid, Alcohol, and Salicylic acid.
7) Excreted through Gastrointestinal tract (GIT): what are excreted are
the ionized matters in the water, Ex. Amino glycosides.
8) Excretion of drugs through Genital organs: especially through the
secretion of the Genital organs, Ex. Cortisone.
Second: Metabolism.
It is the changing of the drug into another chemical form.
The purpose of metabolism is:
Chang the drug to another form of less active and more capable to be
excreted.
More active
Digoxin……….Digitoxine.
Phenobarbitone……….Primidone.
Prednisolone…………Prednisone.
Mechanism and the places where metabolism is carried (done):
1- The liver: is the major center of metabolism in the body, and inside
this organ is carried more than 90% of metabolism process, as it contains
a great amount of enzymes.
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2- There are some drugs are metabolized in the GIT, where in the
membrane of the GIT, which contains enzymes such as Aspirin,
testosterone, isoprenaline.
3- Metabolism by bacteria: Ex. (digoxin, L-dopa, Chloramphenicol, and
sulfadiazine).
4- Metabolism in the blood (the plasma): where enzymes are presents
specially Esterase s enzymes, which hydrolyze the ester compound like
(procaine, hexamethanium and Acetylcholine).
5- Metabolism in the lungs: as it occurs for the prostaglandin.
Metabolic reaction:
1. Constructive (constant).
2. Non-constructive (primary).
Example of non-constructive reaction:
1. Oxidation, Ex. Amphetamine, Ethanol.
2. Hydrolysis, Ex. Procaine, procaine amid, aspirin.
3. Reduction, Ex. Chloralhydrate, Chloramphenicol.
Most of the drug, which had non-constrictive reaction, will be reacted by
constrictive reaction.
Constrictive reaction: norepinephrene, morphine, which will bind to
glucouronic acid.
Factors which depends upon it the metabolism:
1. Places of metabolism.
2. Patients health status.
3. Personal differences.
4. Presence of other drugs, there are some drugs will increase the activity
of enzymes of the liver, so will be different.
Factors that depends on the length of time of activity:
1. To throw with the type of metabolism and excretion.
2. Redistribution.
Example. Barbiturate has a very short time effect, where the activity is
ended fast because of redistribution.
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* Methods of drug administration:
First: Parentral rout.
Where the drug is given directly to the blood stream, and does not need
previous process such as disintegration or absorption and differs by the
way of injection such as:
1) I.V injection: preferences of I.V inj.
1. Used this method in emergencies state.
2. This method is used in the prepared injection such as prepared
solution or powder to be solubilized and prepared during the use.
3. used in injections of nutrients in the cases where food could not be
taken by mouth.
4. Used when need to give solutions by intravenous infusion in large
quantities after operations to substitute body fluids and to return the
blood pressure to its normal state.
5. Most of the times these methods are used in hospitals.
2) Administration of the drug throw artery.
This method is not used usually because it is dangerous and the place of
injection is sunken (deep-seated) and its diameter is small and is used
with:
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a. Anticancer drugs: inorder to reach the drugs to the suffered organ
only, because anticancer drugs have too much side effect so we are
restricting these side effects.
b. To have peripheral effect: as in blood vessels dilators.
3) Intramuscular administration (I.M).
This method is used for the following cases:
1. If the absorption of a drug is very weak from the GIT such as
Gentamicin.
2. If the patient cannot take the drug through the mouth.
Ex. Phenytoin, diazepam, digoxin.
The absorption of these drugs from the GIT is better than through the
intramuscular (I.M) and the reason is that these drugs precipitate in the
place of injection because of the difference in the degree of acidity and it
is very poorly water soluble so its given by mouth or intravenously (I.V).
Factors depended upon the absorption of drugs through the muscle:
1. Blood supply: so it is noted that the absorption of drugs from the arm
is faster than the absorption through the thigh.
2. Degree of ionization of the drug and its solubility.
3. Volume of the injectable: most of the time it is 2ml and does not
exceed 4ml.
4. Osmotic pressure of the solution: sometimes we prepare hypertonic
intramuscular injection internally, inorder to make the absorption faster
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because the blood attempts to decrease the osmotic pressure to normal so
it dissolves better way.
5. Gender (sex) absorption of drugs differs between tow sexes, because
of the distribution of fat in females body is more than in males.
Note: we can give water suspension or oily suspension or water solution
in the muscle.
4) Subcutaneous administration (S.C).
The factors that influence the absorption from the muscle are the same
factors that effects the (S.C) , but here the blood supply is less, so the
absorption is slower than that of the (I.M), but how could it be improved
the absorption process:
1. Make massage and hence increase the blood supply.
2. Warm the place of the injection by heat.
3. Administer with the drug blood vessel dilators (vasodilator) drug.
* Size of the injectable: 1ml or less, and the place of the administration
is the upper part of the arm.
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* It would be better the solvent should not be a suspension or oily
solution because it will cause irritation and pain.
* It is not condition (requirement) but it is better to be equal to the
osmotic pressure of the blood because it does not reach to the blood
stream directly but first reaches the fatty tissue.
* For drugs used subcutaneously is insulin hormone.
5) Intradermal administration (I.d).
Injectable used for that is (0.1- 0.2 ml) volumes, and most of the times
should have the osmocity to be equal with the bloods osmocity and to its
aqueous solution.
* This method of administration is used for the diagnosis purposes such
as diagnosis of tuberculosis by BCG test and also checking for penicillin
sensitivity.
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6) Intra-cardiac administration.
This is method is not used unless in an emergency cases such as when
the heart stops beating.
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7) Intra-thecal.
Cases (situations) where it is used:
1. Used during anesthesia of the cerebrospinal area.
2. Used when sample from the cerebrospinal fluid is withdrawn, Ex. For
the analysis in the laboratory for meningitis.
3. Used to treat meningitis with streptomycin because it passes through
the barrier of blood brain barrier.
* Size of the injectable less than 20ml and osmotically equals to blood
osmotic pressure and the fluid of brain spinal cord.
8) Intra-articular.
This method is used in cases of rheumatic inflammation.
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Second: inhalations.
Absorption through the lung.
Characteristics:
a. The absorption occurs very fast because of great surface area of the
lungs and the blood supplies for the lungs are very high.
b. The drug does not metabolize in the liver because the drug does not
reach to the GIT.
* Some drugs are administrated and absorbed through the lungs:
1. General inhalation anesthetics, Ex. Halothan and ether.
2. Dilators of bronchioles such as Cortisone, Salbutamol.
3. Antihistaminic.
* Factors affecting depended upon the absorption through the lugs:
1. Surface area of the lungs.
2. Blood supply.
3. Degree of acidity.
4. Size of the molecules.
- If the size of the molecule of the drug is large about (20 micrometer) it
will affect the upper respiratory tract such as the throat and larynx.
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- If the size of the molecules are small about (0.6 micrometer) that the
drug will reach the alveoli in faster way, but easily to go out during the
exhalation when breathing.
5. Patient status: grown up (mater) patients need to longer dosages than
the older (senior) patients.
Third: drug administration through the eye.
This method is used inorder to give a local effect and not a systemic
effect, as in the following cases:
Anti-Glaucoma, local anesthetic, pupil dilators, antihistaminic,
inflammation of the eye…..etc.
Pharmaceutical preparations used through the eye:
Ointments, aqueous solution, oily solution, aqueous suspension, oily
suspension.
Factors depended upon the absorption trough the eye:
1. Solubility of the drug in the oils: if the drug is oily soluble, so it's easy
absorbable and passes to the cornea, as in Dexammethazone, it fast
absorbable because it is non-polar, while Dexammethazone phosphate, is
polar, so it is little absorbable.
2. Acidity of the lachrymal (tears) liquid: ph of the eye tears= 7.4 same
as the ph of the blood.
This is important for the stability of the drug if the ph of the drug is
different to that of the lachrymal liquid, then the drug will precipitate
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and will cause irritant of the eye, Ex. (pilocarpine) (which is an alkaloid
has a little alkalinity-high ph) used to treat Glaucoma, so we should take
care so that its ph should be same as that of the ph of the tears, and it can
be amended by the addition of the BUFFER solution.
3. Size of the drop: if the size of the drop will cause to decrease its
effectiveness because its increase drainage from the eye and to increase
time of contact between the eye and the drop we add substances and
thickening agents to increase the adhesives of the drug, Ex. Cellulose
derivatives (thickening agent), and Methyl cellulose, and Carboxyl
methyl cellulose.
4. Pharmaceutical form: it is known that the time of the contact of the
eye ointment with the eye is more than the other pharmaceutical liquid
dosage forms, but the drops are used more of them for following
reasons:
a. Because the aqueous drops have faster effect.
b. Because it mixes with the eye tears.
5. Health state of the eye: the infected eye increases the ability to absorb
drug more than the healthier eye.
6. Age and status of the patient: growing older will decrease the
absorption of the drug, Ex. It was found that the asthmatic patient when
given (Timolol) (is non-selective B- blocker) and it is eye drops and used
to decrease the eye pressure inside the eye ball in Glaucoma, it was
found that small amount of Timolol will pass to the blood stream and
lungs and the asthma patient case will be worsen, this is a very unique
case but to be on the safe side, Timolol will not be given to asthmatic
patient.
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Fourth:Intra-vaginal drug administration.
This is method it's used to treat locally as: the cases of contraceptives,
antifungal and antibacterial.
Ex. Dinoproston is one of the prostaglandin (PGF2OC) used to help in
hastening labour its characteristic is that it is locally used and has no
general side effects as oxytosine.
Pharmaceutical forms of intravaginal drug.
- Vaginal supposes (Tories).
- Vaginal tablets (called tablets because is manufactured by
compression) like Mycostatin (nystatin) - ointment.
- Creams.
- Douches.
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Fifth:Intranasal drug administration.
This method is used to give local effect such as in the case of steroids
anti decongestants.
Also used to give systemic effect such as ADH (anti diuretic hormone)
and until now it is under study and is used to treat Diabetes.
Characteristic of transport and absorption of drugs through the nose:
1. The absorption of the drug is fast and most of it will reach to the blood
stream.
2. The drug is not affected by metabolism.
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Sublingual or
Sixth:
administration
buccal drug
Examples of drugs given sublingual are:
1. Nitroglycen.
2. Isosorbid.
3. Tesfastrem.
4. Methyl testosterone 5- oxytosine.
Characteristics:
1. The drug does not metabolize in the GIT or the liver.
2. Fast drug absorption.
3. Very slow degradation so very long effect, except (isosorbid and
Nitroglycen) both are fast degradable.
The absorption of sublingual drug depend on the degree of acidity of the
drug and the acidity of the saliva, pH= 6.
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Seven’th: Rectal drug administration.
Here the drug is in suppository form or enema given through rectum, and
the drug is given to produce a local effect or a systemic effect as in the
(hemorrhoids) infection of the rectum or as a local, laxative, and for
systemic effect, analgesic for the joints, and as an antipyretics.
This method is used in the following cases:
1. If the patient cannot take the drug through the mouth.
2. If the drug irritant to the GIT or the drug is degradable in the GIT.
Note: there is a saying, if the drug is given through rectum, the
absorption through this part is the same as the absorption through the
GIT, although the blood supply for this part is high and the surface area
is small so the absorption process is little.
Principles that Governs the absorption through the rectum:
1. Solutions are absorbed faster from the suppository and also the
enemas are faster than the suppositories.
2. Absorption through the rectum is changeable more than through the
mouth, for reasons will be explained later.
3. The presence of dried lump of stool in the rectum will delay the
absorption.
4. Bases used in suppositories such as polyethelynglycol may cause
irritation and may lead to loss of the drug.
5. The absorption is carried through the simple transport and not active
transport.
6. This method is not suitable for irritant drugs, such as Tetracycline, and
penicillin.
* Why the absorption through the rectum is changeable?
It depends on the following factors:
1. The region that drug is given the suppository and its remoteness
(farmers).
2. Place of absorption of the drug.
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Factors that are depended upon the absorption through the rectum:
a. Kind (type) of the base used.
b. Period (time) of the drug which stays in the rectum.
c. Pharmaceutical form.
d. Presence of stool.
Good luck
Wish you all the best
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