Zarqa University
Faculty of Pharmacy
Physical pharmacy
Laboratory Manual
(1101220)
Second year
2019/2020
1
Course outline
No.
Experiment
General instructions and Laboratory Safety Rules
1
2
3
Pharmaceutical calculations and prescription labelling
Solubility
Solubilization of drugs (Complexation)
4
Solubilization of drugs (critical micelle concentration)
5
Preparation of Buffers
Midterm Exam
6
Determination of Buffers capacity
7
Liquid dosage forms / Pharmaceutical solution 1
8
Liquid dosage forms / Pharmaceutical solution 2
9
Liquid dosage forms / Pharmaceutical solution 3
10
Liquid dosage forms / Pharmaceutical solution 4
Final Exam
2
Laboratory Safety Rules
Safety is a very important requirement for work in chemical laboratories. Sometimes you will work with
toxic materials, flammable liquids and explosive compounds. If all important precautions are not taken into
consideration, hazardous accidents will occur.
The following rules are very important for your safety as well as the safety of other students. PLEASE read
them carefully and follow them in each laboratory period.
A. Laboratory Safety
Wear safety glass before performing the experimental procedure
Do not eat, drink or smoke in the laboratory
Know where to find and how to use safety and first-aid equipment
Consider all chemicals as hazardous unless you are instructed otherwise
If chemicals come into contact with your eyes or skin, wash immediately with water
and consult your instructor
Wear a white lab coat to protect your clothing
Never taste anything. Never directly smell the source of any vapor
Perform all reactions producing gases or unpleasant odor in the fume hood
Never point a test tube during heating toward yourself or your neighbor
Do not perform any chemical test without being instructed
Clean up all broken glassware immediately
Always pour acids into water and not vice versa
Avoid rubbing your eyes during your work unless you know that your hands are clean
When inserting glass tube or thermometer into stoppers, lubricate the tubing and the
hole in the stopper with grease or water
In case of an accident notify, your instructor immediately
Do not use flammable reagents (alcohol, acetone, and others) near open flame
Learn the location and use of fire protection devices
Do not work alone, always work in the presence of the laboratory instructor
3
B. Instructions for Laboratory Work:
Read the experiment carefully before coming to the laboratory
Report your results directly into your notebook or your data sheet. Do not write on
separate pieces of paper
Perform your experiment with full attention to avoid accidents
Never return reagents to the reagent bottle. Dispose excess reagent in the waste bottle provided by your
instructor
Throw all solids and paper to be discarded into waste paper basket
Never throw matches, filter paper, broken glass or any insoluble materials into the sinks.
Read the label twice before removing anything from the bench
Do not place reagent bottle stoppers on the desk, always hold them in your hand? Never exchange the
stoppers of different bottles
Leave reagent bottles on the shelf where you found them
Use only the amount of reagent specified in the procedure, avoid excesses
Whenever instructed to use water, always use distilled water unless instructed to do
otherwise
When weighing, do not place chemicals directly on the balance
Do not put hot objects on the desk top. Place them on a wire gauze or heat- resistant
pad.
At the end of the each lab. Period leave your glass ware clean and dry on the top of your bench
The following items have to be brought into every lab. Period
•
Dish towel
•
Calculator
•
Matches
•
Sponge for desk cleaning
•
Lab. Coat
•
Lab. Manual
• Eye goggle
4
Experiment no.1
Pharmaceutical calculations and prescription labelling
Aims and objectives
By end of this experiment the student will be:
• Learn how to perform main pharmaceutical calculation required for formulation
• Learn how to label pharmaceutical formulations and how to interpret pharmaceutical prescription
Introduction
Pharmacists are experts on the action and uses of drugs, including their chemistry, the formulation of
medicines and the way in which drugs are used to manage diseases.
Extemporaneous preparation is defined as a drug that is compounded in a pharmacy according to a
prescription (should only be used when manufactured medicines are not available).
Dosage forms are the means by which drug molecules are delivered to sites of action within the body.
There are three dosage forms available:
1. Solid dosage forms: tablets, granules, suppositories and lozenges
2. Liquid dosage forms: drops, gargles, mouthwashes, suspension and emulsions
3. Semisolid dosage forms: creams, gels, ointments and pastes
Labeling of dispensed medicines
Formula for Internal use
Formula for external use
It is the pharmacist responsibility to provide the patient with all information necessary so that the
medicine is used appropriately
5
Labeling of dispensed medicines has two main functions:
1.
To identify the patient with the contents of the container
2.
To insure that the patients have clear and concise information, which will enable them to use
their medicine in the most effective way
The information on the labels of dispensed medicines should be:
1. Accurate: the label should be checked immediately after writing and again prior to fixing to the
containers.
2. Legible: labels should be type written or printed.
3. Intelligible: the information should be very clear and arranged to avoid confusion
4. Adequate and relevant
Standard requirement for labeling:
Main label
1. The name of the patient.
2. Information about the medication has been dispensed
a. The name of the medicine
b.The strength of the medicine.
c. The quantity of the drug in the container
3. The instructions on how and when to use the medication
4. The date of dispensing and expiry date
5. The name and address of the pharmacy
6. Keep out of reach of children
Auxiliary label
Additional information specific to particular medications such as:
The storage conditions of medicine such as:
o Temperature
o Humidity
o Light
Warning or advisory labels such as:
o Shake well before use" for suspensions and emulsions
o "for external use only" for external liquid and semisolid preparations
o "May cause drowsiness" for drugs that cause sedation as a side effect
A batch number should be indicated if the preparation has been prepared extemporaneously or the
shelf life has been shortened e.g. diluted preparation
Additional legal requirements, e.g. "For animal treatment only" or veterinary prescriptions.
Shelf life
The time that a medicine can be kept before the potency has fallen to 90% of the original.
6
Expiry date:
It is usually calculated and expressed by the shelf life
Storing in a cool place means 8–15oC
Refrigerator means 2-8oC
Freshly prepared is defined in the BP as prepared no more than 24 hrs before use but there is no
indication when it should be discarded
Recently prepared is defined in BP as discarded after 4 weeks
Example of labeling
Capsules
Swallow whole with a drought of water
Creams
For external use only
Store in a cool place but do not freeze
Emulsions
Shake the bottle
Suppositories
For rectal use only
Not to be Swallowed
Keep in refrigerator
Nasal drops
For nasal use only
Ointments
For external use only
Gargles and mouth washes
Not to be Swallowed
7
Liniments and lotions
For external use only
Shake the bottle
Avoid application to broken skin
Prescription:
It is an order written by a physician, dentist or any other registered practitioner to a pharmacist to
compound and dispense a specific medication for the patient.
Parts of a prescription:
Date :
Name, sex and address of the patient
Superscription
Rx: recipe "you take"
Inscription
main part
Subscription
less frequent
Signature
"sig": label
Signature, address and registration number of prescribed
Handling of prescription:
1. Receiving
2. Reading and checking
3. Collecting the material
4. Weighing
5. Compounding
6. finishing
8
9
Latin term or phrase
Abbreviation
English meaning
Ante
Auris dextra
Auris laeva
Cibos
Emulsio
Hora
Hora somni
In dies
Inter Cibos
Injection
Laevo
a.
a.d.
a.L.
Cibos
Emul.
h.
h.s.
In.d.
i.c.
Inj.
L
Before
Right ear
Left ear
Food, meal
An emulsion
An hour
At bed time
Daily
During meals
An injection
Left
10
Linimentum
Liquor
Oculoutro
Oculus dexter
Oculus laevus
Omni
Omni hora
Omni mane
Omni nocte
Per os
Recipe
Lin.
Liq.
o.u.
o.d.
o.l.
Omn.
o.h.
o.m
o.n.
p.o.
Rx
A liniment
Solution
Each eye
Right eye
Left eye
Every
Every hour
Every morning
Every night
Orally by mouth
Take
Roman numerals commonly are used in prescription
Calculations for compounding and dispensing
Most of the calculations required for compounding and dispensing involve relatively simple arithmetic.
The welfare of patients depends on the accuracy of pharmaceutical calculations and so careless
calculations cost lives.
Working from a master formula
In extemporaneous dispensing, a list for the quantities and the names of the ingredients is provided on the
prescription. This list for the ingredients and their quantities is called "the master or source formula"
The master formula is obtained from reference sources such as British Pharmacopeias (BP), British
National Formulary (BNF) and United States Pharmacopeias (USP). The master formula lists the
ingredients for the total quantities greater than or less than the amount required to be prepared. The
formula must therefore be scaled down or scaled up as appropriate.
Dealing with percentage concentrations
Many pharmaceutical preparations consist of solution of solids in liquids, solutions of liquids in liquids,
admixture of liquids in solids or mixture of solids with solids. The proportions of the different
components of these systems are often expressed as "percentages". The item "percentage" in
pharmaceutical calculations should be qualified to indicate whether the solution is weight in volume
(w/v), weight in weight (w/w) or volume in volume (v/v).
11
Percentage weight in volume (%w/v):
indicates the number of grams of ingredient in 100 milliliters of product (NOT 100 ml of the vehicle as
water or alcohol)
Percentage weight in weight (%w/w):
Indicates the number of grams of ingredient in 100 grams of product (NOT 100 g of the vehicle as water
or alcohol)
Percentage volume in volume (%v/v):
Indicates the number of milliliters of ingredient in 100 milliliters of product (NOT 100 ml of the vehicle
as water or alcohol).
Example I
Calculate the amounts of the ingredients for 150 ml opiate squill linctus BP 1988.
Ingredients
Master formula BP
Scaled quantities
Squill oxymel
300
50 ml
Camphorated opium tincture
300
50 ml
Tolu syrup
300
50 ml
Total volume
± 900
± 150
Example II
Calculate the amounts of the ingredients for 200 ml Turpentine liniment BP 1988
Ingredients
Master formula BP
Scaled quantities
Soft soap
75 g
15 g
Camphor
50 g
10 g
Turpentine oil
650 ml
130 ml
Water
Up to 1000 ml
Up to 200 ml
In this example the volume of water can't be calculated because a combination of weights and volumes
are present in this formula.
Example III
Calculate the amounts of the ingredients for 60 g of Zinc oxide and calamine paste BP 1988
Ingredients
Master formula BP
Scaled quantities
Zinc oxide
3.75 g
7.5 g
Calamine
15%w/w
9g
Wool fat
7.5 g
15 g
White soft paraffin
Up to 30 g
28.5 g
12
Systems of weights and measures
There are three systems for weights and measures:
1. Metric system (SI)
2. Imperial System
3. Apothecary system
Units of weight
Metric system
Basic Unit
Kilogram (kg)
Imperial system
Pound (Ib) **
Apothecary
system
Grain (gr)
Name of unit
Gram *
Milligram
Microgram
Ounce
Grain
abbreviation
g
mg
mcg
Oz
gr
Scruple
Drachm
Ounce (Apoth.)
-
Relationship
0.001 kg
0.001 g
0.001 mg
1/16 Ib
1/7000 Ib
1/437.5 oz
20 gr
60 gr
480 gr
* 1g = 15.432 gr
** 1 Ib = 0.454 kg
Units of volume
Metric
system
Apothecary
system
Basic Unit
Liter (L)
Minim (m)
Name of unit
Milliliter *
Microgram
Fluid drachm
Fluid Ounce
(Apoth.)
abbreviation
ml
µl
Fl.dr.
Fl.oz
Relationship
0.001 L
0.001 ml
60 minims
480 minims
* 1 ml = 16.23 m
Methods
Give theoretical examples to apply in concepts demonstrated about how to do pharmaceutical calculation,
how to label pharmaceutical formulations and how to interpret pharmaceutical prescription
13
Report sheet (1)
Pharmaceutical calculations and prescription labeling
Student name:
Student No.:
Objectives:
1. How many grams of these ingredients should be used to prepare 60 g of the formula?
Ingredients
Zinc oxide
Calamine
Hydrous wool fat
White soft paraffin
12.5 parts
15 parts
25 parts
47.5 parts
2. If 1 fluid ounce of a cough syrup contains 20 g of sodium citrate, how many mg are contained in
10 ml?
3. Atropine sulfate capsule contains the following ingredients
Ingredients
Atropine sulfate
Codeine phosphate
Aspirin
1/200 gr
1/14 gr
5 gr
How many grams of codeine phosphate you need to prepare 4 capsules?
14
4. What mass of each ingredient is required to prepare 1 pound of cream
Ingredients
White wax
6.25 g
Mineral oil
30 g
Lanolin
1.25 g
Sodium borate
0.5 g
Rose water
12 g
5. Calculate the amount (in mg) of cetyl ester wax required to make 1 Ib of cold cream
Ingredients
Cetyl ester wax
White wax
Mineral oil
Sodium borate
Water
12.5 parts
12 parts
56 parts
0.5 parts
19 parts
15
Experiment no.2
Solubility
Aims and objectives
By end of this experiment the student will be:
• Able to determine the heat of solution of salicylic acid in distil water that accomplished by determining
solubility of salicylic acid in distil water at different temperatures and treating this data according to
Vant Hoff relationship
Introduction
Active pharmaceutical ingredients (APIs) classified into 4 groups on the basis of their solubility and
permeability known as the Biopharmaceutical Classification System (BCS) as shown in the Figure 1.
Figure 1. Biopharmaceutical Classification System (BCS)
Solution is a chemically and physically homogeneous mixture of two or more substances.
When an excess of a solid is brought into contact with a liquid, molecules of the former are removed from
its surface until equilibrium is established between the molecules leaving the solid & those returning to it.
The resulting solution is said to be saturated at the temperature of the experiment, and the extent to which
the solute dissolves is referred to as its solubility.
16
The extent of the solubility of a substance in a specific solvent is measured as the saturation concentration
where adding more solute does not increase the concentration of the solution. The extent of solubility ranges
widely, from infinitely soluble (fully miscible) such as ethanol in water, to poorly soluble, such as silver
chloride in water. The term insoluble is often applied to poorly or very poorly soluble compounds.
Factors affecting solubility
1. Temperature
The solubility of a given solute in a given solvent typically depends on temperature. For many solids
dissolved in liquid water, the solubility increases with temperature up to 100 °C. In liquid water at high
temperatures, (e.g., that approaching the critical temperature), the solubility of ionic solutes tends to
decrease due to the change of properties and structure of liquid water. The solubility of organic compounds
nearly always increases with temperature.
2. Pressure
For condensed phases (solids and liquids), the pressure dependence of solubility is typically weak and
usually neglected in practice.
3. Chemical structure
The chemical structure of the solute usually determines the solute major properties which can influence its
dissolution and bioavailability.The physical properties of the solute such as the crystalline state and
particle size are important in determining its solubility, so minor modifications in the drug molecules (e.g
salt formation or esterfication, micronization to decrease particle size and to increase the effective surface
17
area, and complexation with inert water soluble materials), are strategies that have been used to enhance
the aqueous solubility of these drugs.
4. Solvent: Like dissolve like
Quantification of solubility
Solubility is commonly expressed as a concentration, either by mass (gm of solute per kg of solvent, gm
per dL (100 ml) of solvent), mass concentration, molarity, molality, mole fraction or other similar
descriptions of concentration. The maximum equilibrium amount of solute that can dissolve per amount of
solvent is the solubility of that solute in that solvent under the specified conditions.
In this experiment you will determine the heat of solution of salicylic acid in distilled water. This will be
accomplished by determining solubility of salicylic acid in distilled water at different temperatures and
treating this data according to the Vant Hoff relationship:
Log S = (-∆H /2.303R) (1/T) + constant
Where:
S is the solubility in mole fraction
R is the molar gas constant (0.0821 L. atm /mol.֯ k)
T is the absolute temperature (K)
H is the heat of solution (Kcal/mol)
According to Vant Hoff equation, if you plot log S versus 1/T should yield a straight line with a slope of (∆H /2.303R).
Materials and Apparatus
• Salicylic acid
• Purified water
• 250 ml conical flask with stopper
• Funnel /filter paper
• 100ml graduated cylinder
• 250 ml Beaker
•
•
•
•
•
Volumetric flask 100 ml, 10 ml
Graduated pipit 1ml
Water bath with shaker at temperature
25°c , 50°c, 70°c
Uv-spectrophotometer
Cuvette
Methods
18
1. Determination the aqueous solubility of salicylic acid at 25◦C, 50 ◦C and 70 ◦C.
2. Weigh about 0.5gm salicylic acid in 100ml conical flask. Add 50ml distilled water to make an over
saturated solution.
3. Shake the above solution, in water bath, at the required for 30min.
4. filter to get rid of the excess (insoluble) salicylic acid
5. dilute the filtrate with distilled water (dilute factor 100)
6. Measure the absorbance of diluted salicylic acid at 310nm, using distilled water as solvent.
Note: repeat steps 1-6 at different temperature each time but at 50 ◦C weigh 0.9gm of salicylic acid and 2gm
at 70 ◦C.
19
Report sheet (2)
Solubility
Student name:
Student No.:
Objectives:
Results and discussion:
Temperature
K
Temperature
C
K
Absorbance
Concentration(M)
Solubility of salicylic acid
Mole fraction
1/T
K-1
Dilution
factor
Solubility of
S.A. mole
fraction
Log S
25
50
70
M.wt of salicylic acid =138gm/mol. Absorptivity of salicylic acid = 149.5m2/mol
Calculation and graph
•
Construct a plot of logS Vs 1/T then determine the heat of solution ∆H of salicylic acid in water
using Vant Hoff relationship and the constructed plot
•
Show example of your calculation.
20
21
Discussion
22
Experiment no.3
Solubilization of drugs
Aims and objectives
By end of this experiment the student will be:
• Able to determine the solubility of aspirin in distil water that accomplished by complexing agent sodium
citrate
Introduction
Solubilization is the process by which insoluble or slightly soluble drugs (BCS Class II) become more
soluble. Solubilization can be performed using one of the following methods:
1- Complexation
It defined the co-ordination of compounds, which results from donor acceptor mechanism between two or
more different chemical constituents.
2- Micellar solubilization
Surface active agents have ability to increase the solubility of insoluble or slightly soluble materials in
aqueous solutions through formation of micelles.
Surfactants are compounds that lower the surface tension of the liquid, the interfacial tension between two
liquids or a liquid and solid. Surfactants are amphiphilic molecules that contain the hydrophobic
hydrocarbon tail and hydrophilic head. Therefore, surfactant molecule contains both a water soluble and
water insoluble (or oil soluble) component.
A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous
solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent.
Micelle formation is essential for the absorption of fat-soluble vitamins and complicated lipids within the
human body. Bile salts formed in the liver and secreted by the gall bladder allow micelles of fatty acids to
23
form. This allows the absorption of complicated lipids (e.g., lecithin) and lipid soluble vitamins (A, D, E
and K) within the micelle by the small intestine.
3- Salt formation
Salt is formed from the reaction of an acid with a base. This simple chemical reaction Salt formation may
be used to alter the physicochemical, biopharmaceutical, and processing properties of a drug substance
without modifying its fundamental chemical structure. In general, the salts of a drug rarely change its
pharmacology; however, the intensity of response may be altered.
The solubility of acidic drugs or basic drugs may be enhanced through the addition of a basic or an acidic
substance respectively this is due to the ionization resulting in the salt formation which has higher solubility
in water.
In practice, the hydrochloride salts of basic drugs and the sodium salts of acidic drugs are the most common.
4- Cosolvency
Cosolvents are defined as water-miscible organic solvents that are used in liquid drug formulations to
increase the solubility of poorly water-soluble substances or to enhance the chemical stability of a drug.
Cosolvency, then, refers to the technique of using cosolvents; it is also commonly referred to as solvent
blending.
The use of cosolvents to prepare solution formulations of non-polar drugs is a simple and potentially
effective way to achieve high concentrations of drug. The primary disadvantages of cosolvency include the
potential for biological effects including: their general toxicity, target organ toxicity, tissue irritation and
the potential for drugs that have been solubilized using cosolvents to precipitate upon dilution with aqueous
fluids.
5- Heating
In endothermic dissolution type the solutes solubility is enhanced through heating of solution.
24
Materials and Apparatus
• Aspirin
•
Sodium citrate
•
•
•
•
Phenolphthalein
Purified water
250 ml conical flask with stopper
Funnel /filter paper
•
•
•
•
•
•
•
100 ml graduated cylinder
250 ml Beaker
Conical flask 250 ml
Graduated pipit 10 ml
25 ml Burette
Magnetic stirrer
Water bath with shaker at temperature
25°c
Methods
1. Take 7 clean conical flasks, place 1.5 gm of aspirin powder accurately weighed in each one
2. Add to each flask one of the following amount of sodium citrate where the first is considered as
blank.
3. Add to each flask 50ml of distilled water accurately measured.
4. Shake for 5 minutes; allow standing for 10minutes then filtering.
5. Discard the first 5ml of the filtrate.
6. Take 10ml of the filtrate and titrate with 0.1N NaOH using phenolphthalein as indicator.
25
Report sheet (3)
Solubilization of drug
Student name:
Student No.:
Objectives:
Results and discussion:
Weight of sodium
citrate (gm)
0
0.5
1
1.5
2
2.5
3
volume of NaOH
(ml)
Moles of aspirin in
10ml solution
Moles of aspirin in
50ml solution
Calculation and graph
1. Calculate the amount of aspirin solubilized in each 50ml H2O?
2. Plot the amount of aspirin solubilized versus the amount of sodium citrate added.
3. Determine the minimum amount of sodium citrate that gives maximum solubility of 1gm of aspirin?
4. Find the solubility of aspirin?
26
27
Discussion
28
Experiment no.4
Solubilization of drug
Critical Micelle concentration
Aims and objectives
By end of this experiment the student will be:
• Able to determine the solubility of cresole in distil water that accomplished by micellar Solubilization
• Able to Find critical micellar concentration
Introduction
Surfactants are molecules with well defined polar and non-polar regions that allow them to aggregate in
solution to form micelles. Non-polar drugs can partition into these micelles and be solubilized .
Depending on the nature of the polar area, surfactants can be
•
•
•
•
nonionic (e.g., polyethylene glycol, span , tween )
anionic (e.g., sodium dodecyl sulfate)
cationic (e.g., trialkylammonium),
zwitterionic (e.g., glycine and proteins).
Figure 1.
Surfactants display distinct behavior when interacting with water. The polar part of the molecule seeks to
interact with water while the non-polar part shuns interaction with water. There are two ways in which such
a molecule achieve both these states. An amphiphilic molecule can arrange itself at the surface of the water
such that the polar part interacts with the water and the non-polar part is held above the surface (either in
the air or in a non-polar liquid) as shown in Figure B above. The presence of these molecules on the surface
29
disrupts the cohesive energy at the surface and thus lowers the surface tension. Such molecules are called
‘surface active’ molecules or surfactants.
Another arrangement of these molecules can allow each component to interact with its favored environment.
Molecules can form aggregates in which the hydrophobic portions are oriented within the cluster and the
hydrophilic portions are exposed to the solvent. Such aggregates are called micelles. An example of a
spherical micelle is diagrammed above (illustration C).
Micelle formation
The proportion of molecules present at the surface or as micelles in the bulk of the liquid depends on the
concentration of the amphiphile.
At low surfactant concentration the surfactant molecules arrange on the surface. When more surfactant is
added the surface tension of the solution starts to rapidly decrease since more and more surfactant molecules
will be on the surface. When the surface becomes saturated, the addition of the surfactant molecules will
lead to formation of micelles. This concentration point is called critical micelle concentration.
Critical micelle concentration (CMC): is the concentration above which the micelles are formed
When surfactants are present above the CMC they can act as emulsifiers that will allow a compound that
is normally insoluble (in the solvent being used) to dissolve. This occurs because the insoluble species can
be incorporated into the micelle core, which is itself solubilized in the bulk solvent by virtue of the head
groups favorable interactions with solvent species.
It follows that measurement of surface tension may be used to find CMC. A graph of surface tension versus
log of concentration of surfactant added will appear as follows:
In this graph you can see three phases:
1. At very low concentrations of surfactant only slight change in surface tension is
detected.
2. Additional surfactant decreases surface tension
3. Surface becomes fully loaded, no further change in surface tension.
30
As shown above the technique for assaying CMC by measurement of surface tension is simple and
straightforward. A graph of surface tension versus log concentration is produced. The CMC is found as the
point at which two lines intersect; the baseline of minimal surface tension and the slope where surface
tension shows linear decline.
Materials and Apparatus
•
•
•
•
Du Noüy ring Tensiometer
7 Test tubes
Test tube rack
Dropper
Methods
1. Using the Du Noüy ring to determine the surface tension of each sample for the different
concentration included in the table.
31
1. Take a set of seven test tubes place in each test tube 10ml of the given concentration of potassium
oleate solution.
2. Place 10ml of distilled water in another test tube.
3. Using a dropper add drops of cresol to each test tube drop by drop cover each test tube and shake
well after each addition
4. Leave to equilibrate
5. Observe the produced solution of cresol in soap solution you are to observe the clarity or
turbidity of the solution
6. Continue addition of cresol drops as long as you have a clear solution the end point will be the
separation of cresol as a new phase
7. Record the end point which is the number of drops of cresol consumed before phase separation
8. Convert numbers of drops into volumes (ml) knowing that 1ml of cresol=22drops.
32
Report sheet (4)
Solubilization of drug (CMC)
Student name:
Student No.:
Objectives:
Results and discussion:
Soap concentration (M)
End point
Drops of cresol
Volume of cresol (ml)
0
0.01
0.05
0.1
0.2
0.3
Surfactant concentration
(M)
Surface tension (dyne/cm)
Capillary
Du noy
Pure water
Calculation and graph
1. Plot the X-axis (amount soap concentration (M)) Y-axis (volume of cresol consumed (ml))
2. Plot surface tension Vs log surfactant concentration
3. From the graphs determine CMC.
4. water surface tension is --------------33
34
Discussion
35
Experiment no. 5
Preparation of Buffers
Aims and objectives
By end of this experiment the student will be:
• Able to perform calculation required for preparation of buffer solution at variable pH value
Introduction
A buffer solution is an aqueous solution consisting of a mixture of a weak acid and its conjugate base or a
weak base and its conjugate acid. It has the property that the pH of the solution changes very little when a
small amount of strong acid or base is added to it. Buffer solutions are used as a means of keeping pH at a
nearly constant value in a wide variety of chemical applications.
Strong acids (e.g., HCl) and bases (e.g., NaOH) almost completely ionize in water:
Many acids and bases, however, do not undergo complete ionization in water. These compounds, then, are
called weak acids and bases.
The dissociation of a weak acid is described by the following reaction:
One can analyze the strength of a weak acid. This means that the amount of hydrogen ion released can be
determined. To do this, one can use the following expression:
Where Ka: acid dissociation constant.
36
The larger the value of Ka, the stronger the acid is. Because Ka values vary over a wide range, they are
usually expressed using a logarithmic scale:
Therefore acids with the lowest pKa values are able to dissociate in solutions of low pH, i.e. even where the
hydrogen ion concentration is high. Acids with higher pKa values dissociate only in solutions of high (more
alkaline) pH.
pH has been defined as the negative logarithm of the hydrogen ion concentration:
The Henderson-Hasselbalch equation provides a convenient way to think about buffers and pH:
The Henderson-Hasselbalch equation can be used to determine if an aqueous solution of a conjugate
acid/base pair is functioning as a buffer. The most convenient form of this equation is:
Example:
How would you prepare 10mL of a 0.02M acetate buffer, pH 4.30, from stock solutions of 0.05M
acetic acid (HAc) and 0.05M NaOH? pKa acetic acid = 4.76.
-
1. Use the Henderson Hasselbalch equation to find the ratio of A to HA.
-
pH = pKa + log [A ] / [HA]
-
4.30 = 4.76 + log [A ] / [HA]
-
-0.46 = log [A ] / [HA]
-
0.34673685 = [A ] / [HA]
37
2. Calculate the decimal fraction (part/whole) of each buffer component.
-
A = 0.34673685 / (1.00 + 0.34673685) = 0.34673685 / 1.34673685 = 0.257464441
HA = 1.00 / 1.34673685 = 0.742535559
3. Find the molarity (M) of each component in the buffer by simply multiplying the molarity of the buffer
by the decimal fraction of each component.
-3
MA- = 0.02M x 0. 257464441= 0.005149289 = 5.15 x 10 M
-2
MHA = 0.02M x 0. 742535559= 0.014850711 = 1.49 x 10 M
4. Calculate the moles of each component in the buffer. Moles = Molarity x Liters
-5
molesA- = 0.005149289M x 0.01L = 5.14929 x 10 moles
-4
molesHA= 0.014850711M x 0.01L = 1.485071.47 x 10 moles
5. Since this buffer is prepared by the reaction of a weak acid (HAc) with a strong base (NaOH), you must
determine the total moles of the weak acid component needed because the conjugate base is made in
situ.
-5
-4
-4
Total moles = 5.15 x 10 moles NaOH + 1.49 x 10 moles HAc= 2.00 x 10 moles HAc. This sum indicates
-4
-5
that, although in the buffer one only needs 1.49 x 10 moles HA, an additional 5.15 x 10 moles is needed
to generate the conjugate base in situ.
6. Calculate the volume of each stock solution required to make the buffer
Liters of stock = Moles of the buffer component / Molarity of the stock
-5
-3
LA= 5.14929 x 10 moles / 0.05 M = 1.03 x 10 L NaOH = 1.0mL
-4
-3
LHA = 2.00 x 10 moles / 0.05 M = 4.00 x 10 L CH3COOH = 4.0mL
➢ To prepare this buffer, one would use appropriately sized pipets or cylinders to measure and transfer 1ml
of NaOH and 4ml of Ac.Ac. to a 10 mL volumetric flask and bring the solution to volume with distil
H2O.
Materials and Apparatus
• Sodium hydroxide 2 N
•
•
•
•
Acetic acid 1 M
Distil water
Funnel
100 ml graduated cylinder
•
•
•
•
•
•
250 ml Beaker
Conical flask 250 ml
Graduated pipit 10 ml
Volumetric flask 100 ml
Dropper
PH meter
38
Methods
Prepare 100 ml buffer solutions of 0.3M acetic acid and sodium acetate of the following pH 4, 4.5, 5.5
and 5.7 values using 1M acetic acid and 2 N NaOH stock solutions, knowing that the pKa of acetic acid
is 4.75.
1) Measure acetic acid and sodium hydroxide exactly by pipit and transfer to volumetric flask 100 ml
2) Adjust the volume by distil water
3) Shake volumetric flask
4) Measure PH value by PH meter
39
Report sheet (5)
Preparation of Buffers
Student name:
Student No.:
Objectives:
Prepare 100 ml buffer solutions of 0.3M acetic acid and sodium acetate of the pH values equal to ---------------- using 1M acetic acid and 2 N NaOH stock solutions, knowing that the pKa of acetic acid is 4.75.
Calculation:
40
Experiment no. 6
Determination of buffer capacity
Aims and objectives
By end of this experiment the student will be:
• Able to determine buffer capacity for different buffer concentration
Introduction
The magnitude of the resistance of a buffer to pH changes is referred to as the buffer capacity β. It also is
known as buffer efficiency, buffer index and buffer value.
Van Slyke introduced the concept of buffer capacity and defined it as the ratio of increment of strong base
(or acid) to small change in ph brought about by this addition. For the present discussion, the approximate
formula, may be used
β=ΔB
Δ pH
Equation 1
In which delta Δ has it’s usual meaning, a finite change, and ΔB is the small increment in gram
equivalent./liter of strong base added to the buffer solution to produce a pH change of Δ pH.
 The buffer capacity calculated from equation (1) is only approximate. It gives the average buffer capacity
over the increment of base added.
 Van Slyke developed a more exact equation for calculation of buffer capacity β
β = 2.3 C
Ka[H3O+]
)Ka + [H3O+])2
 Where C is the total buffer concentration, that is, the sum of the molar concentrations of the acid and the
salt.
 A concentration of 0.05 to 0.5 molar is sufficient and a buffer capacity of 0.01 to 0.1 is sufficient.
In buffer solution If the concentration of the weak acid is equal to that of its conjugate base, the ratio of
these two components is one, and then Henderson-Hasselbalch equation reduces to
pH = pKa
When the pH of the solution is equal to the pKa of the ionizing group, the solution is functioning at
maximum buffering capacity (best buffer).
41
Aqueous solution functions as a good buffer when the pH of the solution is within approximately one pH
unit of the ionizing group’s pKa.
pH = pKa + 1
Buffers function as follows: when a strong acid is added, the H+ from that acid combine with a portion of
the anion to form undissociated acid, thereby removing most of the added H+ from the solution
H+ + A-
HA
When strong base is added part of the undissociated acid reacts to form anions
Base + HA
A- + Base-H+
42
Materials and Apparatus
•
•
•
•
•
•
Acetate buffer at PH =5 with concentration 0.1 m , 0.2 m
M HCL
M NaOH
250 ml beaker
10 ml pipit
PH meter
Methods
1- You are provided with 2 acetate buffers, pH=5. Each with different concentrations ; 0.1 M and 0.2 M .
2- Transfer 20 ml of each buffer into a 50 ml beaker.
3- Measure their PH befor either addition of acid or base
4- Add 0.2 ml of 0.1M HCl from the burette and determine the pH of the solution after each addition
5- Continue adding acid in until pH falls to about 1 pH units from your starting pH .
6- Plot a Curve of pH versus ml of HCl added and calculate the Buffer capacity
7- Then compare between two buffer which one has higher buffer capacity and why?
8- Repeat the previous steps , except add 0.1M NaOH
43
Report sheet (6)
Determination of buffer capacity
Student name:
Student No.:
Objectives:
Result and disscusion :
a) 0.1 M acetate buffer pH = 5
Amount of
acid
added
pH before
addition of
acid
pH after
addition of
acid
∆ PH after
acid addition
Buffer capacity
after acid
addition
pH after
addition of
base
∆ PH after
base addition
Buffer capacity
after base
addition
b) 0.1 M acetate buffer pH = 5
Amount of
base
added
pH before
addition of
base
44
c) 0.2 M acetate buffer pH = 5
Amount of
acid
added
pH before
addition of
acid
pH after
addition of
acid
∆ PH after
acid addition
Buffer capacity
after acid
addition
pH after
addition of
base
∆ PH after
base addition
Buffer capacity
after base
addition
d) 0.2 M acetate buffer pH = 5
Amount of
base
added
pH before
addition of
base
Calculation and graph
•
•
Plot a Curve of pH versus ml of HCl added and calculate the Buffer capacity
Then compare between two buffer which one has higher buffer capacity and why?
45
46
Discussion
47
Experiment no.7
Liquid dosage form
Pharmaceutical solutions 1
Aims and objectives
By end of this experiment the student will be:
• Able to prepare some oral aqueous pharmaceutical solutions by variable methods of preparation
Introduction
Solutions are “liquid preparations that contain one or more chemical substances dissolved in a suitable
solvent or mixture of mutually miscible solvents”. Because of a particular pharmaceutical solution’s use,
it may be classified as oral, otic, ophthalmic, or topical.
Advantages of Solutions
1) Therapeutic agents can easily be administered orally to individuals who have difficulty in swallowing,
e.g. elderly patients, infants.
2) The therapeutic agent is dissolved in the formulation and is therefore immediately available for
absorption. Providing the drug does not precipitate within the gastrointestinal tract, the bioavailability
of pharmaceutical solutions is greater than that of oral solid-dosage forms.
3) Taste-masking of bitter therapeutic agents may be readily achieved.
4) Homogenous therefore give uniform dose than suspension or emulsion which need shaking
Disadvantages of Solutions
(1) Bulky therefore difficult to transport and store.
(2) Unpleasant taste or odors are difficult to mask.
(3) Needs an accurate spoon to measure the dose.
(4) Less stable than solid dosage forms.
Stability of solutions
Both the chemical and the physical stability of solutions in their intended containers are important. A
solution must retain its initial clarity, colour, odour,taste and viscosity over its allocated shelf-life.
48
Additives
1-Buffers
Used to resist any change in pH
Examples of buffer salts used in pharmaceutical solutions include:
■ acetates (acetic acid and sodium acetate): 1–2%
■ citrates (citric acid and sodium citrate): 1–5%
■ phosphates (sodium phosphate and disodium phosphate): 0.8–2%.
2-Isotonicity modifiers
Solutions for injection, for application to mucous membranes, and large-volume solutions for ophthalmic
use must be made iso-osmotic with tissue fluid to avoid pain and irritation.The most widely used
isotonicity modifiers are dextrose and sodium chloride.
3-Viscosity enhancement
The viscosity of the formulation must be sufficiently controlled in order to ensure the accurate
measurement of the volume to be dispensed. Furthermore, increasing the viscosity of some formulations
may increase the palatability. Certain liquid formulations do not require the specific addition of viscosityenhancing agents, e.g.syrups, due to their inherent viscosity.
The viscosity of pharmaceutical solutions may be easily increased (and controlled) by the addition of nonionic or ionic hydrophilic polymers. Examples of both of these categories are :
■ non-ionic (neutral) polymers
Methylcellulose , hydroxyethylcellulose, hydroxypropylcellulose , polyvinylpyrrolidone
■ ionic polymers
sodium carboxymethylcellulose (anionic), sodium alginate (anionic).
4-Preservatives
Ideally, preservatives should exhibit the following properties:
■ Possess a broad spectrum of antimicrobial activity
■ Be chemically and physically stable over the shelf-life of the product
■ Have low toxicity.
49
Preservative used:
•
Alcohols
Ethanol is useful as a preservative when it is used as a solvent. It needs a relatively high
concentration (> 10%) to be effective.
Propylene glycol also used as a solvent in oral solutions and topical preparations. It can function as a
preservative in the range of 15 to 30%. It is not volatile like ethanol.
•
Acids
Benzoic acid and sorbic acid have low solubility in water. They are used in a concentration range
from 0.1 % to 0.5% and (0.05–0.2%). Only the non-ionized form is effective and therefore its use is
restricted to preparations with a pH below 4.5
•
Esters
Parabens are esters (methyl, ethyl, propyl and butyl) of p-hydroxybenzoic acid.
They are used widely in pharmaceutical products and are effective and stable over a pH range of 4 -8.
They are employed at concentrations up to about 0.2%. Frequently 2 esters are used in combination in
the same preparation
•
Quaternary Ammonium Compounds
Benzalkonium chloride is used at a relatively low concentration 0.002 to 0.02%. This class of compounds
has an optimal activity over the pH range of 4 to 10 and is quite stable at most temperatures. Because of the
cationic nature of this type of preservative it is incompatible with many anionic compounds.
5-Antioxidants
• Antioxidants are included in pharmaceutical solutions to enhance the stability of therapeutic agents that
are susceptible to chemical degradation by oxidation.
• Examples of antioxidants that are commonly used for aqueous formulations include: sodium sulphite,
sodium metabisulphite, and ascorbic acid.
• Examples of antioxidants that may be used in oil-based solutions include: butylated hydroxytoluene
(BHT), butylatedhydroxyanisole (BHA) and propyl gallate.
50
• Typically antioxidants are employed in low concentrations (0.2% w/w). Antioxidants may also be
employed in conjunction with chelating agents, e.g. ethylenediamine tetraacetic acid, citric acid, that act
to form complexes with heavy-metal ions, ions that are normally involved in oxidative degradation of
therapeutic agents.
6-Sweetening agents
Sweetening agents are employed in liquid formulations designed for oral administration to increase the
palatability of the therapeutic agent. The main sweetening agents employed in oral preparations are sucrose,
Sucrose has the advantage of being colourless, very soluble in water, stable over a pH range of about 4-8
and, by increasing the viscosity of fluid preparations, will impart to them a pleasant texture in the mouth. It
will mask the tastes of both salty and bitter drugs and has a soothing effect on the membranes of the throat.
Polyhydric alcohols such as sorbitol, mannitol and, to a lesser extent glycerol, also possess sweetening
power and can be included in preparations for diabetic use. The use of artificial sweetening agents saccharin
sodium and aspartame not required at a concentration greater than about 0.2%., in many formulations,
saccharin sodium is used either as the sole sweetening agent or in combination with sugars or sorbitol to
reduce the sugar concentration in the formulation.
7-Flavours and colorants
Flavours is often required to mask the taste of the drug substance . The four basic taste sensations are
salty, sweet, bitter and sour. It has been proposed that certain flavours should be used to mask these
specific taste sensations.
■ Usually a combination of flavours is used to achieve the optimal taste-masking property.
51
■ Certain excipients may be added to oral solution formulations, referred to as flavour adjuncts (e.g.
menthol, chloroform) that add flavour to the formulation but, in addition, act to desensitise the taste
receptors.
Colours : The selected colour should ‘match’ the flavour of the formulation, e.g. green with mint-flavoured
solutions, red for strawberry-flavoured formulations. Although the inclusion of colours is not a prerequisite
for all pharmaceutical solutions
Classification of Solutions According to Vehicle
Aqueous
1. Douches
2. Enemas
3. Gargles
4. Mouthwashes
5. Nasal washes
6. Juices
7. Sprays
8. Otic solutions
9. Inhalations
Sweet &/or Viscid
1. Syrups
2. Honeys
3. Mucilages
4. Jellies
Nonaqueous
1. Elixirs
2. Spirits
3. Collodions
4. Glycerins
5. Liniments
6. Oleo Vitamin
Aqueous Solutions
Aqueous solutions are homogeneous mixtures that are prepared by dissolving a solid, liquid or gas in an
aqueous medium (vehicle). this may be water, aromatic water or extracts.
Water
Water is used both as vehicle and as a solvent for the desired flavoring or medicinal ingredients.
Advantages: Tasteless, odorless, lack of pharmacological activity, neutral & very cheap
1. Purified Water
Must be used for most pharmaceutical operations and in all the tests and assays. Such water is prepared by
distillation, deionization or reverse osmosis. Ultraviolet energy, heat or filtration (Millipore filtration)
can be used to remove or kill the microorganisms present in the water.
52
2. Aromatic Waters
Aromatic waters are clear, aqueous solutions saturated with volatile oils or other aromatic or volatile
substances. Most of the aromatic substances in the preparation of aromatic waters have very low solubility
in water, and even though the water may be saturated, its concentration of aromatic material is still rather
small.
Aromatic waters may be used for perfuming and/or flavoring. Volatile oils solutions represent an
incompatibility problem of salting out. This occurs after the incorporation of a very soluble salt in their
solution. Aromatic water will deteriorate with time therefore:
• Should be made in small quantities
• Protected from intense light and excessive heat by storing in air tight, light resistant containers.
If they become cloudy or otherwise deteriorate; they should be discarded. Deterioration may be due to
volatilization, decomposition or mould growth.
Methods of Preparation of Solutions
(a) Simple Solution
(b) Solution by Chemical Reaction
(c) Solution by Extraction
Materials and Apparatus
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Potassium permanganate
Magnesium carbonate
Anhydrous citric acid
Syrup
Lemon oil
Talc
Sodium bicarbonate
Rose oil
250 ml Conical flask
Glass rod
Watch glass
Beaker
Hot plate
Magnetic stirrer.
Balance
Funnel /filter paper
Vacuum filtration flask
•
•
•
•
Mortar & pestle
Volumetric flask
100 ml Cylinder
Amber / transparent bottle
53
Methods
Formula (1)
Rx . 100 ml Potassium permanganate 0.2% solution
Ingredients
Master formula
Potassium permanganate
1g
Water up to
500ml
Scaled formula
100ml
Procedure
1. Weigh potassium permanganate in 50 ml beaker
2. Mix the crystals with small 50 ml of water using magnetic stirrer.
3. Pouring off the resulting solution into container Complete the volume to 100ml in the bottle.
Formula (2)
Rx 100ml Magnesium citrate oral solution USP
Ingredients
Master formula
Magnesium carbonate
15 g
Anhydrous citric acid
27.4 g
Syrup
60 ml
Lemon oil
0.1 ml
Talc
5g
sodium bicarbonate
2.5 g
Purified Water up to
350 ml
Scaled formula
100 ml
Procedure
1. Weigh citric acid on watch glass
2. Dissolve citric acid in 40 ml of hot purified water in Erlenmeyer flask
3. Weigh magnesium carbonate, dissolve in 30 ml purified water in another flask, then, add
slowly to citric acid solution and stir until it is dissolved.
4. Add syrup and mix.
5. Heat the mixed liquid to the boiling point.
6. Immediately add lemon oil previously triturated with talc.
54
7. Filter the hot mixture into bottle previously rinse with purified water
8. Add water to produce 100 ml
9. Allow mixture to cool.
10. Add sodium bicarbonate, shake to dissolve.
Formula (3)
Rx 100ml rose water
Ingredients
Master formula
Rose oil
2 ml
Talc
30 g
Purified water ad.
1000 ml
Scaled formula
100 ml
Procedure
1. In a mortar, triturate talc with rose oil & add little amount of water dropwise to make a paste.
2. Dilute the paste with the rest amount of water dropwise until it became pourable.
3. Transfer to a clean bottle and shake for 5 minutes.
4. Filter through a filter paper wetted with water in erlenmeyer flask 250 ml .
5. Transfer to 100 ml graduated cylinder and adjust the volume if necessary after filtration.
6. Transfer to a clean bottle and fix the label.
55
Report sheet (7)
Liquid dosage form
Pharmaceutical solutions 1
Student name:
Student No.:
Objectives:
Formula (1)
Rx . 100 ml Potassium permanganate 0.2% solution
Ingredients
Master formula
Potassium permanganate
1g
Water up to
500ml
Scaled formula
100ml
•
Pharmaceutical calculations
•
Label the product with direction for preparing 1 Litre of 0.0125% solution for use.
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
56
• Formula (2)
Rx 100ml Magnesium citrate oral solution USP
Ingredients
Master formula
Magnesium carbonate
15 g
Anhydrous citric acid
27.4 g
Syrup
60 ml
Lemon oil
0.1 ml
Talc
5g
Sodium bicarbonate
2.5 g
Purified Water up to
350 ml
•
Scaled formula
100 ml
Pharmaceutical calculations
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
• Formula (3)
Rx 100ml rose water
Ingredients
Master formula
Rose oil
2 ml
Talc
30 g
Purified water ad.
1000 ml
•
Scaled formula
100 ml
Pharmaceutical calculations
57
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
58
Experiment 8
Liquid dosage form
Pharmaceutical solutions 2
Aims and objectives
By end of this experiment the student will be:
• Able to prepare some types of Douches, Enemas, and gargles
Introduction
Douches
Solutions may be prepared from powders or from liquid solutions or liquid concentrates. In using liquid
concentrates, the patient is instructed to add the prescribed amount of concentrate (usually a teaspoonful
or capful) to a certain amount of warm water (frequently a quart). The resultant solution contains the
appropriate amount of chemical agents in proper strength. Douche powders are used for their hygienic
effects. A few douche powders containing specific therapeutic anti-infective agents
Enemas
Enemas are rectal injections
Retention Enemas
▪ A number of solutions are administered rectally for
▪ local effects (e.g., hydrocortisone) (e.g. anthelmintic property)
▪ systemic absorption (e.g., aminophylline), rectal administration minimizes the undesirable
gastrointestinal reactions associated with oral therapy.
▪ they may contain radiopaque substances for roentgenographic examination of the lower bowel.
▪ Retention enemas are used in small quantities (about 30ml) and are thus called retention microenema.
Evacuation Enemas
▪ Rectal enemas are used to cleanse the bowel.
▪ Are solutions of sodium phosphate and sodium biphosphate, glycerin and docusate potassium, and
light mineral oil.
▪ Starch enema may be used either by itself or as a vehicle for other forms of medication
• Mouthwash/Gargle:
Aqueous solutions for the prevention and treatment of mouth and throat infections, to reduce plaque,
gingivitis, dental caries and stomatitis can contain antiseptics, analgesics and/or astringents.
59
- Cosmetic mouthwashes may be formulated to reduce bad breath through the use of antimicrobial
and/or flavoring agents.
- They are usually diluted with warm water before use.
Material and apparatus
• Alum
• Boric acid
• Glycerin
• Starch powder
• Turpentine oil
• Phenol/ glycerin (16%w/w)
• Amaranth solution(1%w/v)
• Boiled water
• Distil water
•
•
•
•
•
•
•
•
•
250 ml Conical flask
100 ml Cylinder
Glass rod
Funnel /filter paper
Amber / transparent bottle
Balance
Beaker
Hot plate
Mortar and pistol
Methods
Formula (1)
Rx 100 ml cleansing douche
Ingredients
Master formula
Alum
2g
Boric acid
1g
Glycerin
20 ml
Purified water to
500 ml
Scaled formula
100 ml
Procedure
1. Measure 70 ml of worm water in a conical flask.
2. Dissolve alum, boric acid in the water with aid of glass rod till complete solution occurs.
3. Filter the resulting solution in in a conical flask.
4. Transfer to 100 ml graduated cylinder.
5. Wash flask of filtration by 20 ml water and transfer to the graduated cylinder and adjust the final
volume.
6. Transfer to a suitable bottle and fix the label.
60
Formula (2)
Rx 100 ml Starch enema
Ingredients
Master formula
powdered starch
3g
cold purified water
20 ml
Boiling water to
100 ml
Scaled formula
Procedure
1. Triturate 3 g. of powdered starch with 20 ml, of cold water to form a thin paste
2. Sufficient boiling water is added to make 100 ml. of enema.
3. Reheat to obtain a transparent liquid.
4. Cool and adjust to volume.
Formula (3)
Rx50 ml Turpentine enema
Ingredients
Turpentine oil
Master formula
5ml
Starch enema to
100 ml
Scaled formula
50
Procedure
1. Place of starch enema in 100 ml bottle.
2. Add turpentine oil dropwise with vigorous shaking after each addition.
3. fix the label with shake the bottle as auxiliary label..
Formula (4)
Rx 100 ml phenol glycerin gargle
Ingredients
Phenol glycerin (16% w/w)
Master formula
50 ml.
Amaranth solution (1%w/v)
10 ml.
Water to
1000 ml.
Scaled formula
100 ml
Formula for phenol glycerin (16% w/w)
Ingredients
Phenol
Master formula
16 g.
glycerin
84g.
Scaled formula
Total
5 ml
• Density of glycerin = 1.26 g/ml , Density of phenol = 1.06 g/ml
61
• Phenol and glycerin are mixed in a beaker. The beaker is warmed gently until is becomes a
solution.
Procedure
1. Accurately measure phenol glycerin and amaranth solution separately.
2. Mix amaranth solution with 20 ml of purified water and add phenol glycerin by continuous stirring
with glass rod.
3. Transfer this content to 100ml graduated cylinder and add sufficient amount of purified water to
produce final volume.
62
Report sheet (8)
Liquid dosage form
Pharmaceutical solutions 2
Student name:
Student No.:
Objectives:
• Formula (1)
Rx 100 ml cleansing douche
Ingredients
Master formula
Alum
2g
Boric acid
1g
Glycerin
20 ml
Purified water to
500 ml
• Pharmaceutical calculations
Scaled formula
100 ml
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
63
Formula (2)
Rx 100 ml Starch enema
Ingredients
Master formula
powdered starch
3g
cold purified water
20 ml
Boiling water to
100 ml
•
Scaled formula
Pharmaceutical calculations
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
Formula (3)
Rx50 ml Turpentine enema
Ingredients
Turpentine oil
Starch enema to
•
Master formula
Scaled formula
5ml
100 ml
Pharmaceutical calculations
50
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
64
Formula (4)
Rx 100 ml phenol glycerin gargle
Ingredients
Phenol glycerin (16% w/w)
Master formula
50 ml.
Amaranth solution (1%w/v)
10 ml.
Water to
1000 ml.
Scaled formula
100 ml
Formula for phenol glycerin (16% w/w)
Ingredients
Phenol
Master formula
16 g.
Scaled formula
Glycerin
84g.
5 ml
•
Pharmaceutical calculations
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
65
Experiment 9
Liquid dosage form
Pharmaceutical solutions 3
Aims and objectives
By end of this experiment the student will be:
• Able to prepare some types of medicated and simple syrup, elixir , and liniment
Introduction
Syrups
Syrups are highly concentrated, aqueous solutions of sugar or a sugar substitute that contain a
flavouring agent, e.g.cherry syrup, cocoa syrup, orange syrup, raspberry syrup. An unflavoured syrup
is available that is composed of an aqueous solution containing 65%w/w (85% w/v) sucrose.
The major components of syrups are as follows:
▪ Purified water.
▪ Sugar (sucrose) or sugar substitutes (artificial sweeteners).
Traditionally syrups are composed of sucrose (usually between 65 and 85%) and purified water.
▪ Preservatives. Preservatives are not required in syrups containing high concentrations of sucrose.
Conversely, in sugar-free syrups, syrups in which sucrose has been substituted at least in part by
polyhydric alcohol and in traditional syrups that contain lower concentrations of sucrose, the
addition of preservatives is required.
▪ Flavours. These are employed whenever the unpalatable taste of a therapeutic agent is apparent,
even in the presence of the sweetening agents.
▪ Colours. These are generally selected according to the flavour of the preparation.
It is important that the concentration of sucrose approaches but not quite reach the saturation
point, WHY?
• In dilute solutions sucrose provides an excellent nutrient for molds, yeasts, and other
microorganisms.
• In concentration of 65 % by weight or more the solution will retard the growth of such
microorganisms
•
A saturated solution may lead to crystallization of a part of the sucrose under conditions of
changing temperature.
66
Preparation of Simple Syrup
(a) Solution with heat
This is the usual method of making syrups in the absence of volatile agents or those injured by heat,
When it is desirable to make the syrup rapidly. The sucrose is added to the purified water or aqueous
solution and heated until dissolved, and then strained and sufficient purified water added to make the
desired weight or volume.
When heat is used in the preparation of syrups, there is almost certain to be an inversion of a slight
portion of the sucrose.
C12H22O11
Sucrose
2 C6H12O6
heat & acid
Invert sugar (dextrose and levulose)
Invert sugar
• Is more readily fermentable than sucrose
• Tend to darken in color
• Retard the oxidation of other substances.
• The levulose formed during inversion is sweeter than sucrose; therefore the resulting syrup is
sweeter than the original syrup.
• When syrup is overheated it caramelizes.
(b) Agitation without Heat
•
This process is used in those cases where heat would cause loss of valuable volatile constituents.
•
The syrup is prepared by adding sucrose to the aqueous solution in a bottle of about twice the size
required for the syrup. This permits active agitation and rapid solution.
c) Addition of a Medicating Liquid to syrup
• This method is resorted to in those cases in which fluid extracts, tinctures, or other liquids are added
to syrup to medicate it.
• Syrups made in this way usually develop precipitates since alcohol is often an ingredient of the
liquids thus used and the resinous and oily substances dissolved by the alcohol precipitate when
mixed with syrup.
• A modification of this process consists of mixing the fluid extract or tincture with the water,
allowing the mixture to stand to permit the separation of insoluble constituents, filtering & and then
67
dissolving the sucrose in the filtrate. This procedure is not permissible when the precipitated
ingredients are the valuable medicinal agents.
Preservation of Syrups
• The USP suggests that syrups be kept at a temperature not above 25°C.
• Preservatives such as glycerin, methyl paraben, benzoic acid and sodium benzoate may be added to
prevent bacterial and mold growth, particularly when the concentration of sucrose in the syrup is
low.
• The official syrups should be preserved in well dried bottles and stored in a cool dark place.
Non-aqueous pharmaceutical solutions
1. Alcoholic or hydroalcoholic solutions, e.g. elixirs and spirits,
2. Ethereal solutions, e.g. the collodions
3. Glycerin solutions, e.g. the glycerites,
4. Oleaginous soIutions e.g. the liniments, medicated oils, oleo-vitamins, sprays, and
toothache drops.
Advantages
▪ If the drug is not completely soluble or unstable in aqueous medium it may be necessary to use an
alternative non-aqueous solvent.
Elixirs
An elixir is a clear, hydroalcoholic solution that is formulated for oral use. The concentration of
alcohol required in the elixir is unique to each formulation and is sufficient to ensure that all of the
other components within the formulation remain in solution.
The typical components of an elixir are as follows:
■ Purified water.
■ Alcohol. Generally the concentration of alcohol is greater than 10% v/v; however, in some
preparations, the concentration of alcohol may be greater than 40% v/v.
■ Polyol co-solvents. e.g. propylene glycol, glycerol, may be employed in elixirs to enhance the
solubility of the therapeutic agent and associated excipients.
■ Sweetening agents.
■ Flavours and colours. All pharmaceutical elixirs contain flavours and colours to increase the
palatability and enhance the aesthetic qualities of the formulation.
68
Incompatibility of elixir:
♦ Alcohol precipitates water soluble substances e.g. tragacanth, acacia agar and many inorganic salts
from aqueous solutions.
♦ If an aqueous solution is added to an elixir, a partial precipitation of ingredients may occur. This is
due to the reduced alcoholic content of the final preparation.
Liniments
Liniments are alcoholic or oleaginous solutions or emulsions of various medicinal substances intended
to be rubbed on the skin. Liniments with an alcoholic or hydroalcoholic vehicle are useful when
rubefacient, counterirritant, or penetrating action is desired; oleaginous liniments are employed
primarily when massage is desired. By their nature, oleaginous liniments are less irritating to the skin
than alcoholic liniments.
Liniments are not applied to skin areas that are broken or bruised because excessive irritation might
result.
All liniments should bear a label indicating that they are suitable only for external use and must never
be taken internally. Liniments that are emulsions or that contain insoluble matter must be shaken
thoroughly before use to ensure even distribution of the dispersed phase, and these preparations should
be labeled shake well. Liniments should be stored in tight containers.
Rubefaciant
A substance for external application that produces redness of the skin e.g. by causing dilation of the
capillaries and an increase in blood circulation.
Counterirritant
A medicine applied locally to produce superficial inflammation in order to reduce deeper
inflammation
Materials and apparatus
•
•
•
•
•
•
•
•
•
•
Sucrose
Compound orange spirit
Syrup
Talc
Ethanol
Iron Ammonium Citrate
Cherry syrup
Camphor
Methyl salicylate
Arachis oil
•
•
•
•
•
•
•
•
•
Distil water
250 ml Conical flask
Glass rod
Beaker
Balance
Funnel /filter paper
Mortar & pestle
100 ml Cylinder
Amber / transparent bottle
69
Methods
Formula (1)
Rx 50gm simple syrup B.P. 1980
Ingredients
Master formula
Sucrose
667gm
Purified Water up to
1000gm
Scaled formula
50gm
Procedure
1. Heat water with sucrose on hot plate 200-250 ºC until clear solution
2. Filter when it is hot using cotton.
Formula (2)
Rx 50ml aromatic elixir N.F. 1980
Ingredients
Master formula
Scaled formula
Compound orange spirit
12ml
0.6ml (12 drops)
Syrup
375ml
Talc
30gm
Alcohol
240ml
Water up to
*Compound orange spirit
Orange oil
2.4ml
Lemon oil
0.6ml
Coriander oil
0.24ml
Anise oil
0.06ml
1000ml
50ml
Procedure
1. Use 0.6 ml of orange spirit and add to them 12ml alcohol and mix well in Erlenmeyer flask
2. Add syrup portion wise with vigorous shaking
3. Add water potion wise until completing volume to 50ml
4. Add talc and shake.
5. Filter using filter paper wetted with alcohol
70
Formula (3)
Rx 60 ml iron ammonium citrate syrup
Ingredients
Iron Ammonium
Citrate
Master formula
5g
Water
2.5 ml
Cherry syrup q.s.
60 ml
Scaled formula
Procedure
1. Powder Iron Ammonium Citrate in a glass mortar.
2. In a beaker, put 2/3 amount of vehicle.
3. Sprinkle Iron Ammonium Citrate in small amounts in water to avoid formation of undissolved mass. Stir
after each additionand filter if necessary through cotton wool wetted with water.
4. .Add the Iron amm. citrate solution as dropwise to the contents of the syrup beaker with
continuous mixing the mixture with glass rod
5. Transfer to a graduated cylinder and fix the final volume
6. Transfer to a clean bottle and fix the label
Formula (4)
Rx 10ml camphor and methyl salicylate liniment
Ingredients
Master formula
camphor
20gm
Methyl salicylate
40ml
Arachis oil up to
1000ml
Scaled formula
10ml
Procedure
1. Mix camphor and methyl salicylate in the final container
2. Add arachis oil and shake
71
Report sheet (9)
Pharmaceutical solutions 3
Student name:
Student No.:
Objectives:
Formula (1)
Rx 50gm simple syrup B.P. 1980
Ingredients
Master formula
Sucrose
667gm
Purified Water up to
1000gm
•
Scaled formula
50gm
Pharmaceutical calculations
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
72
Formula (2)
Rx 50ml aromatic elixir N.F. 1980
Ingredients
Master formula
Scaled formula
Compound orange spirit
12ml
0.6ml (12drops)
Syrup
375ml
Talc
30gm
Alcohol
240ml
Water up to
1000ml
50ml
• Pharmaceutical calculations
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
Formula (3)
Rx 60 ml iron ammonium citratesyrup
Ingredients
Iron Ammonium
Citrate
Master formula
5g
Water
2.5 ml
Cherry syrup q.s.
60 ml
Scaled formula
• Pharmaceutical calculations
73
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
Formula (4)
Rx 10ml camphor and methyl salicylate liniment
Ingredients
Master formula
camphor
20gm
Methyl salicylate
40ml
Arachis oil up to
1000ml
•
Pharmaceutical calculations
•
Labeling
Scaled formula
10ml
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
74
Experiment 10
Liquid dosage form
Pharmaceutical solutions 4
Aims and objectives
By end of this experiment the student will be:
• Able to prepare linctuses, glycerites , and liniment
Introduction
Glycerites
Are solutions or mixtures of medicinal substances is not less than 50% by weight glycerin. Most of glycerites are
extremely viscous and some of them are of a jelly-like consistency.
The advantages of glycerin in these preparations are:
[1] A valuable solvent, being composed of a polar and non-polar groups, it has a wide range of solvent power.
[2] Its sweet taste.
[3] Has a preservative action.
[4] Stable.
[5] Miscible with water and alcohol, thus liquid glycerites can serve as stoke solution
which may be diluted with water or alcohol.
Linctuses
linctus is a viscous preparation, usually prescribed for the relief of cough. It normally consists of a simple
solution of the active agent in a high concentration of sucrose, often with other sweetening agents. This
type of product, which is also designed to be administered in multiples of 5 mL, should be sipped slowly
and not be diluted beforehand. The syrup content has a demulcent action on the mucous membranes of the
throat. For diabetic use the sucrose is usually replaced by sorbitol and/or synthetic sweeteners.
Spirits
Spirits are alcoholic or hydroalcoholic solutions of volatile substances. Generally, the alcoholic
concentration of spirits is usually over 60%. Because of the greater solubility of aromatic or volatile
substances in alcohol than in water, spirits can contain a greater concentration of these materials than
75
the corresponding aromatic waters. Spirits may be used pharmaceutically as flavoring agents and
medicinally for the therapeutic value of the aromatic solute. For medicinal purposes, spirits may
be taken orally, applied externally, or used by inhalation, depending upon the particular
preparation. When taken orally, they are generally mixed with a portion of water to reduce the
pungency of the spirit.
Materials and Apparatus
•
•
•
•
•
•
•
•
•
•
•
Benzoic Acid solution
Chloroform spirit
Lemon syrup
Simple syrup
Starch
Benzoic acid
Distil water
Phenol
Glycerin
Methyl salicylate
Olive oil
•
•
•
•
•
•
•
•
•
•
•
Codeine Phosphate
Compd. Tartarazine solution
250 ml Conical flask
Glass rod
Beaker
Balance
Funnel /filter paper
100 ml Cylinder
Amber / transparent bottle
Hot plat
Thermometer
Methods
Formula (1)
Rx50 ml Scar Phenol ear drops BPC
Ingredients
Master formula
Phenol glycerin
20 ml
Glycerin to
50 ml
Scaled formula
Procedure
1. Phenol and glycerin are mixed in a beaker. The beaker is warmed gently until is becomes a
solution.
2. Add glycerin with continuous mixing the mixture with glass rod
3. Transfer to a graduated cylinder and fix the final volume
4. Transfer to a clean bottle and fix the label
76
Rx phenol glycerin
Ingredients
Phenol
Master formula
160 g.
Glycerin
840 g.
Scaled formula
• Density of glycerin = 1.26 g/ml
• Density of phenol = 1.06 g/ml
Formula (2)
• Rx25ml Methyl salicylate liniment Bp.
Ingredients
Methyl salicylate
Master formula
25 ml
Scaled formula
Olive oil to
100 ml
25 ml
Procedure
1. In a mortar, mix methyl salicylate with ½ amount of olive oil by using the pestle.
2. Transfer to a cylinder, and complete to final volume with the oil.
3. Transfer to a clean bottle, fix a label.
Formula (3)
Rx50 ml Codeine Linctus, Paediatric B.P.C.
Ingredients
Codeine Phosphate
Compd. Tartarazine
solution
Benzoic Acid
solution
Chloroform spirit
Master formula
Scaled formula
0.3 g
1 ml
2 ml
2 ml
Water
2 ml
Lemon syrup
20 ml
Simple syrup to
100 ml
50 ml
Procedure
1. Codeine phosphate is weighed and taken in a conical flask.
2. Water is added to the flask, heated gently to dissolve.
3. Color, benzoic acid solution and chloroform spirit are added one at a time and
77
4. mixed thoroughly after each addition.
5. Lemon syrup is added and mixed. Syrup is added and mixed.
6. Transfer to a clean bottle and fix the label.
Formula (4)
Rx50 mlStarch Glycerite USP
Ingredients
Master formula
Starch
100g
water
200mL
Benzoic acid
2g
Glycerin
700mL
Scaled formula
50 ml
Procedure
1. Heat glycerin to 120-1240C (check the temperature with a thermometer).
2. Make suspension of the starch and benzoic acid in the calculated amount of water.
3. Add aqueous suspension to the heated glycerin after reaching the assigned temperature, and stir with
a glass rod in cross lines until translucent jelly-like mass is produced. We stir in cross lines to
prevent the formation of air bubbles.
4. Leave to cool then Transfer to a clean bottel and fix the label.
78
Report sheet (10)
Pharmaceutical solutions 4
Student name:
Student No.:
Objectives:
Formula (1)
Rx50 ml Scar Phenol ear drops BPC
Ingredients
Master formula
Phenol glycerin
20 ml
Glycerin to
50 ml
Scaled formula
Rxphenol glycerin
Ingredients
Phenol
Master formula
160 g.
Glycerin
840 g.
•
Scaled formula
Pharmaceutical calculations
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
Formula (2)
79
• Rx25ml Methyl salicylate liniment bp.
Ingredients
Methyl salicylate
Master formula
25 ml
Scaled formula
Olive oil to
100 ml
25 ml
•
Pharmaceutical calculations
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
Formula (3)
Rx50 ml Codeine Linctus, Paediatric B.P.C.
Ingredients
Codeine Phosphate
Compd. Tartarazine
solution
Benzoic Acid
solution
Chloroform spirit
Master formula
Scaled formula
0.3 g
1 ml
2 ml
2 ml
Water
2 ml
Lemon syrup
20 ml
Simple syrup to
100 ml
•
Pharmaceutical calculations
•
Labeling
50 ml
80
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
Formula (4)
Rx50 mlStarch Glycerite
Ingredients
Master formula
Starch
100g
water
200mL
Benzoic acid
2g
Glycerin
700mL
•
Scaled formula
50 ml
Pharmaceutical calculations
• Labeling
Main label
Name of patients:- --------------------Name of preparation :-------------------Dosage Form:--------------------------------Strength:------------------------Production date:--------------------- expiry date:-------------------Instruction:----------------------------------------------Uses:-----------------------Auxiliary label
81