PRINCE SATTAM BIN
ABDULAZIZ UNIVERSITY
COLLEGE OF PHARMACY
DEPARTMENT OF PHARMACEUTICS
AL-KHARJ
KINGDOM OF SAUDI ARABIA
Laboratoual
LABORATORY MANUAL CUM LOGBOOK
PHARMACEUTICS III
PHT- 322
LEVEL VI
Name of the student:___________________________________
Course Co-ordinator
Student ID No:_______________________________________
Dr. Mohammad Javed Ansari
ACADEMIC YEAR
1439-1440
 This manual will serve only as model
type.
 The content of experiment or
experiment
partially
or
fully
substituted depending upon the
availability
of
chemical
and
instrument.
 There may be more than the
prescribed experiments to explore
the understanding of theory topics.
 The content used is reproducible
only after permission from the
supervisor.
 The product prepared is only for
laboratory use and research.
 During
experiment
all
the
participants have to follow strict
GMP/ GLP rules to avoid occurrence
of any untoward incidence.
DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL PHT 322
Page 2
DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL PHT 322
Page 3
Introduction & grading policy
Principles and techniques involved in this course deal with the formulation,
preparation, and evaluation of solid dosage forms. The following main subjects will
be
covered:
pharmaceutical
powders
including
physical
properties,
flow
characteristics, preparation of bulk and divided powders, tablets design and
manufacturing, effervescent granules, capsule preparations, evaluation and
manufacturing, and suppositories dosage forms including preparation and
evaluation.
GRADING
Contents
Experiment / discipline
Laboratory Record
Lab Exam
Viva/ synopsis
Total
Grades
5
5
10
5
25
Week
Every week
Every week
13-14
13-14
NECESSARY INSTRUCTIONS
1.
All students must complete all laboratory assignments. If a lab is missed, the
reason for the absence must be discussed with the instructor and a
makeup lab arranged attend the same in free time by discussion with concerned
supervisor.
2.
3.
Submit the home work whenever instructed for the same.
The content of experiment or experiment partially or fully substituted
depending upon the availability of chemical and instrument.
There may be more than the prescribed experiments to explore the
understanding of theory topics.
4.
DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL PHT 322
Page 4
CONTENT OF LABORATORY EXPERIMENTS
Weeks Experiment
1
2
3
4
6
AIM:- Evaluation of flow properties of
the powder
7
AIM:- Preparation of effervescent granules
8
AIM:- Capsule dosage forms filling and
evaluation
9
AIM:- Preparation of tablet dosage forms
(granules)
AIM:- Evaluation of granules (sieve
analysis)
AIM:- Evaluation of Tablets.
12
Signature of
instructor
AIM:- Preparation and dispensing of
compound powders
AIM:- Preparation and dispensing of
powders for topical / external
applications
AIM:- Preparation and dispensing of
powders with special problems
11
Lab Record (5)
AIM:- Preparation and dispensing of
simple powder
AIM:- Preparation and dispensing of
potent powders
5
10
QC/Lab
discipline (5)
AIM:- Preparation of granules
Suppositories.
Note: All grading should be accompanied by signature of Lab instructor.
Note 2: Lab record must be checked on or before next experiment. (Late submission means
losing 1 grade/day)
Note 3: Final Lab exam (10) + viva/ synopsis/ other activities/ (5)
DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL PHT 322
Page 5
Lab Indiscipline (-5)
EXPSt Name/ID
DATE:
Late
Attendance
entry
(-1)
No lab
coat
(-1)
SECTION:
Dirty
Lab
Dirty
Glass
Indiscipline Workplace
wares ((-1) (-1)
1)
DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL PHT 322
Page 6
DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL PHT 322
Page 7
EXPDATE-
EXPDATE-
EXPDATE-
EXPDATE-
EXPDATE-
EXPDATE-
1 – Attendance; 2 - Late entry; 3 - No lab coat (-1); 4 - Lab Indiscipline (-1); 5 - Dirty Workplace (-1); 6 - Dirty Glass wares (-1)
STUDENT
NAME/ ID
DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL PHT 322
Page 8
EXPDATE-
EXPDATE-
EXPDATE-
EXPDATE-
EXPDATE-
EXPDATE-
1 – Attendance; 2 - Late entry; 3 - No lab coat (-1); 4 - Lab Indiscipline (-1); 5 - Dirty Workplace (-1); 6 - Dirty Glass wares (-1)
STUDENT
NAME/ ID
PHT 322,382 SECTION
Experiment 1
Student Name:
Student ID:
AIM:- Preparation and dispensing of simple powder
Theory:
Simple powders are oral powders containing one ingredient only which are weighed, and
dispensed as undivided (bulk powder in large container) or divided (wrapped in individual
papers in divided doses) to be taken once, twice or thrice as prescribed by physician.
Undivided oral powders (bulk powder) are usually non-potent medicaments, such as antacids,
where the accuracy by which the patient measures the dose is not critical. These are supplied in
large container with spoon to administer the dose.
Divided powders are generally potent powders where dosage accuracy is very importance;
therefore every dose should be individually weighed, packaged and dispensed for the use by
patient.
In this experiment, you are supposed to prepare and dispense antacid powder such as magnesium
hydroxide or any alternative powder such as magnesium oxide, magnesium carbonate. As an
antacid, magnesium hydroxide is dosed at approximately 0.5–1.5 g in adults and works by
simple neutralization, where the hydroxide ions from the Mg (OH)2 combine with acidic H+
ions produced in the form of hydrochloric acid by parietal cells in the stomach to produce water.
Procedure:
1- Reduce the particle size of powder if it is crystalline / granular by grinding it in mortar and
pastels.
2- Pass the powder through appropriate sieve.
3- Weigh the calculated amount and pack in suitable size of container
4- Lable the container for appropriate dosage.
Directions:
Indication:
Home Work
Discuss advantages and disadvantages of powders as dosage forms.
PHT 322,382 SECTION
Experiment 2
Student Name:
Student ID:
AIM:- Preparation and dispensing of potent powders
Theory:
Potent powders are powders with relatively lower therapeutic doses such as milligram or
microgram doses. For instance potent drugs like fentanyl, alprazolam, risperidone evoke a given
response at low concentrations, while a drug of lower potency such as paracetamol, ibuprofen etc
evoke response only at higher concentrations. Thus Potency is a measure of drug activity
expressed in terms of the amount required to produce an effect of given intensity.
The potency depends on both the affinity and efficacy. Affinity is how well a drug can bind to a
receptor (Fast/strong binding = higher affinity) [D]. Efficacy is the ability a drug to initiate a
response at the cellular / tissue level (Effect, E). Increasing drug concentration [D] increases
effect E until at sufficiently high concentrations it can no longer be increased by raising [D] and
asymptotes to a maximum Emax. The Emax is the maximum possible effect for the agonist. The
concentration of D at which E is 50% of Emax is termed the half maximal effective
concentration and is abbreviated [D]50, or more commonly EC50. The term "potency" refers to
the [D]50 value. The lower the [D]50, the less the concentration of a drug is required to produce
50% of maximum effect and the higher the potency.
Therapeutic doses of potent powders are low enough to weigh and dispense accurately using
dispensing balances without dilution. Therefore dispensing of potent powders should be done by
using sensitive balances or dispensing balances after aliquoting (weighing sufficient quantity of
mixture of inert material and required dose of potent drug).
Before aliquoting, you need to calculate the total amount of inert material needed to be mixed
with the total dose of potent drug. Once both powder and inert material is calculated and
weighed, these must be mixed by geometric dilution (mixing and doubling technique) followed
by aliquot weighing, dividing, and packaging individual doses to be used by patient.
First of all, least weighable quantity (LWQ) is calculated for the balance using this formulaLeast weighable quantity (LWQ) = 100 x Sensitivity of balance / permissible % error
Secondly, find out the factor (factor = LWQ / quantity or dose of potent drug requested ͌ full
number). Thirdly multiply this factor with dose of drug and LWQ to find amount of potent drug
and the diluent to be mixed together. Finally, divide mixture total weight by the factor in step 2
to get amount to be weighed for one dose.
PHT 322,382 SECTION
Experiment 2
Student Name:
Student ID:
In this experiment, we are going to learn how to dispense 2 mg of Atropine Sulfate (5 doses,
SOS). It is used as cholinesterase Inhibitors in case of organophosphates, carbamates poisoning
Procedure:

Use protective equipment such as gloves, face mask, lab coat and safety glass during
handling of potent drugs.

Reduce the particle size of powder if it is crystalline / granular by grinding it in mortar
and pastels.

Pass the powder through appropriate sieve.

Calculate the amount of potent drug (all doses plus one extra dose to take care of losses
during weighing and packaging).

Weigh the calculated amount of potent powder taking care of LWQ. (LWQ = 100 x
Sensitivity of balance / permissible % error (generally 5% error is allowed)

Note that total dose of potent drugs should be > LWQ of balance, if it is less then find out
weighing factor, weighing factor = LWQ / single dose of potent powder (total dose to be
weighed with accuracy is = single dose x weighing factor)

Calculate the amount of diluent required (= total drug dose x weighing factor)

Weigh calculated amount of inert powder (diluent such as lactose, glucose etc) previously
grounded and sieved (if necessary).

Mix total dose of potent powder (x gram) with approximately equal amount of diluent (x
gram) in the mortar by gentle trituration.

Add approximately double amount (2x grams) of diluent in the mixture (mortar) now and
triturate gently.

Add approximately double amount (4x grams) of diluent in the mixture (mortar) now and
triturate gently.

Repeat this procedure until you finish all diluent.

Prepare weighing paper of suitable size (folded and marked)

Weigh single dose of mixture containing 2 mg of atropine sulfate (x / 2 = total mixture /
total drug) and pack it.

Repeat this until you prepare all requested doses.

Pack all doses in suitable size envelope with complete labelling.
PHT 322,382 SECTION
Experiment 2
Student Name:
Student ID:
Home Work
Write briefly about potent powder, aliquoting and geometric dilution.
If sensitivity of a balance is 0.001g and permissible error in the weighing is 5%, then calculate
the least weighable quantity of the balance. Also calculate potent powder and diluent to be
weighed if dose is 5 mg.
If sensitivity of a balance is 0.001g and permissible error in the weighing is 4%, then calculate
the least weighable quantity of the balance. Also calculate potent powder and diluent to be
weighed if dose is 10 mg
PHT 322,382 SECTION
Experiment 3
Student Name:
Student ID:
AIM:- Preparation and dispensing of compound powders
Theory: Compound powders are powder mixture that contain more than one active ingredient. It
can be dispensed as divided powder (individual doses in wrappers or sachet) or as a bulk
powder.
Divided compound powders:
Compound aspirin powders
Aspirin
Paracetamol
300 mg
150 mg
Compound antacid powders
Omeprazole
Sodium bicarbonate
20 mg
1680 mg
Compound oral rehydration powder
Sodium chloride
Sodium citrate
Potassium chloride
Glucose
3.5 g
2.5 g
1.5 g
20 g
Undivided (Bulk) compound powders
Compound antacid powders
Sodium bicarbonate
12.5 g
Magnesium carbonate 37.5 g
Calcium carbonate
37.5 g
Bismuth carbonate
12.5 g
Compound powders are prepared by weighing and grinding every component separately
followed by mixing them in ascending order of weight or amount.
Aim: Prepare and dispense two doses of compound oral rehydration powder.
Compound oral rehydration powder
Sodium chloride
Sodium citrate
Potassium chloride
Glucose
3.5 g
2.5 g
1.5 g
20 g
Procedure:
1- Calculate the amount of each component needed for the total doses.
2- Calculate and add 5% excess of each component to take care of losses during mixing and
dividing the doses.
3- Weigh each component and grind gently in mortar to reduce the particle size of powder if
it is crystalline / granular. Keep each component separately.
4- Add each component in mortar in ascending order of their weights and mix or blend by
gentle trituration.
5- Weight sufficient amount for single dose if it is divided powder or weigh the total
quantity to be dispensed if it is bulk powder.
6- Label it properly with all required information
Compound oral rehydration powder
Pharmaceutical Ingredients
Quantity
Sodium chloride
3.5 g
Sodium citrate
2.5 g
Potassium chloride
1.5 g
Glucose
20 g
Quantity for
5
% TOTAL
required dosage
Excess
Home Work
Discuss briefly about low osmolarity oral rehydration salts.
PHT 322,382 SECTION
Experiment 4
Student Name:
Student ID:
AIM:- Preparation and dispensing of powders for topical / external applications
Theory: Powders for topical or external applications are very finely divided simple or compound
powder mixtures prepared and supplied in bulk (multi-doses), therefore these are also known as
bulk powders / undivided powder.
There are several kind of bulk powders.
Dusting Powders:
These are locally applied nontoxic very finely divided bulk powder dispensed in sifter-top
packages. Dusting powders are applied to various parts of the body as lubricants, protectives,
absorbents, antiseptics, antipruritics, astringents and antiperspirants.
Medical dusting powders:
Used mainly for superficial skin conditions, should be free from pathogenic microorganisms.
Talc and kaolin are generally used as diluents because these are chemically inert. However, since
such ingredients are readily contaminated with pathogenic bacteria, these must be sterilized by
dry heat method(160 °C for 2 hours) before their use.
Surgical dusting powder:
Used in body cavities and also on major wound or burns and umbilical cords of infants, therefore
surgical dusting powders must be sterilized. They usually contain sterilize able diluents such as
cornstarch which is also absorbable. Therefore starch containing bulk powders are also called as
absorbable dusting powders. It was used in the past to prevent surgical gloves from sticking.
However,it is no longer used as may cause foreign body reaction (starch granuloma),powderfree gloves are used instead.
Insufflations: - These are finely divided bulk powders dispensed into an insufflator (powder
blower) intended to be insufflated / introduced into body cavities such as the ears, nose, throat,
tooth sockets and vagina.
Dentifrices: - Dentifrices are very finely divided bulk powder for dental applications.
These powders generally contain detergent, mild abrasive and an anticariogenic agents.
Douche Powders: - Douche are completely soluble powders intended to be dissolved in water
prior to use as antiseptics or cleansing agents for a body cavity such as vaginal, nasal, otic or
ophthalmic.
Oral bulk powders:
Bulk powders are generally locally applied external powders, however, some antacid and
laxative powders can be supplied as bulk compound powders without diluent, whereas external
bulk powders generally contains diluents like Talc, Starch, magnesium oxide etc.
Aim: Prepare and dispense dusting powder.
Corn starch
Light magnesium oxide
or
Talc
Calcium Carbonate
98 g
2g
99 g
1g
g
Send 10 g
Sig.: To be used as lubricant / skin protectant
Procedure:
1. Powdered all the ingredients.
2. Weigh the required quantity of all the ingredients with 5-10% excess to take care of
losses.
3. Mix them in ascending order of their weight.
4. Pass the mixed powder through a sieve no.85 or higher.
5. Transfer the powder in sifter top containers to protect it from atmospheric contamination.
Pharmaceutical Ingredients
Quantity
5 % Excess
TOTAL
Home Work
Discuss about types of bulk powders
PHT 322,382 SECTION
Experiment 5
Student Name:
Student ID:
AIM:- Preparation and dispensing of powders with special problems
Theory:
Preparation and dispensing of powders with certain features such as volatile nature, hygroscopic
nature, non-crystalline gummy nature, eutectic mixtures etc. require special techniques, control
and attention.
Volatile Substances
The loss by volatilization may be prevented or retarded by use of heat-sealed plastic bags or by
double wrapping with a waxed or glassine paper inside of a bond paper.
Hygroscopic powders
Some powders become moist when exposed to air because of affinity for moisture in the air. Salt
(NaCl), Sugar (Sucrose), CaO, NaNO3, and CuO. therefore these may be prepared as divided
powders by adding inert diluents such as magnesium carbonate, kaolin, lactose. Doublewrapping is desirable for further protection.
A- Should be made in a granular form to decrease the exposed surface to air.
B- Should be packed in aluminum foil or in plastic film packets
C- Should be mixed with light magnesium oxide to reduce the tendency to damp
D- Should be mixed with adsorbent materials such as starch, talc, kaolin etc
Note: some hygroscopic materials are used as desiccants (adsorb moisture from atmosphere and
keep the environment dry). Eg Silica gel, activated charcoal, calcium sulfate, calcium chloride,
and molecular sieves (typically, zeolites). Silica gel is a granular, vitreous, porous form of silicon
dioxide made synthetically from sodium silicate.
Note: Some hygroscopic substance are used as humectant (absorb moisture from environment to
keep things moist). Humectant is the opposite of a desiccant. It is often a molecule with several
hydrophilic groups capable of making hydrogen bonding with water molecules. eg Glycerin used
in pastes to prevent it from drying.
Deliquescence powders
Extremely hygroscopic powders that absorb large amount of moisture form air and liquefy due to
absorption of moisture hence these cannot be prepared satisfactorily as powder preparation. Eg
NaOH, KOH, MgCl2, CaCl2, CaCl2.6H2O, FeCl3 etc.
Efflorescent powders
Crystalline substances containing water of crystallization loose their water of crystallization at
exposure or during storage and change to powder (reduced weight) or sometime liquefy ( the
liberated water of crystallization convert the powder to a paste or to a liquid). Eg.
Na2SO4.10H2O, Na2CO3.10H2O, FeSO4.7H2O. Alum (KAl(SO4) 2· 12H2O), moohydrates of
atropine sulfate / citric acid /codeine phosphate etc.
A-Use anhydrous form of the compound
B-Treat it in a manner similar to hygroscopic powders
Eutectic Mixtures
Some powder materials such as phenol, camphor, menthol, thymol, antipyrine, phenacetin,
acetanilid, aspirin, salol and related compounds may liquefy when mixed in mortar even at
ordinary temperatures. Such mixture are called as eutectic mixtures.
A-Such powders should be supplied separately. or
B-Inert adsorbent such as starch, talc, kaolin are added to prevent dampness of the powder
These powders must be triturated individually with some inert diluent / adsorbant material
followed by gentle mixing with each other.
Explosive mixtures
Oxidizing agents (ex. Pot. Salts of chlorate, dichromate, permanganate and nitrate- Sod.
Peroxide- silver nitrate and silver oxide) explore violently when triturated in a mortar with a
reducing agent ( ex. sulfides- sulfur- tannic acid- charcoal).
Solution:
A- Comminute each salt separately.
B- Subject to a minimum pressure.
Gummy powders
Some non-crystalline powders are gummy in nature and tend to reagglomerate / resist grinding,
hence cannot be powdered normally using trituration in mortar and pestle. However, these may
be powered by addition of a volatile solvent which help in size reduction of gummy material and
can be easily removed by vaporization. This techniques is called as pulverization by Intervention.
Eg Camphor with addition of alcohol or other volatile solvent can be reduced readily to a fine
powder. Similarly, iodine crystals may be comminuted with the aid of ether.
Aim: Prepare and dispense 0.5 g of camphor powder (4 doses)
Procedure:
1. Weigh the required quantity of the camphor with 20-25% excess to take care of losses.
2. Triturate it after adding few drops of alcohol or other volatile solvent.
3. The pulverized camphor is readily recovered as the solvent evaporates.
4. Divide the doses and pack in suitable wrapper.
5. Labe and dispense the medicine.
Indication: supplied as cream, lotion or liniment with menthol 0.5% each.
It is used topically as rubefacient/counter-irritant medication. It is also used in liniments as a
counter-irritant for fibromyalgia, neuralgia, and similar conditions. In dermatology, when it is
applied as lotion (0.1 to 3%), it is an anti-pruritic and surface anesthetic (when applied gently, it
creates a feeling of coolness). By vapor inhalation it is used as cough suppressant and
decongestant.
Home Work
Classify the powders using different classifications.
PHT 322,382 SECTION
Experiment 6
Student Name:
Student ID:
AIM:- Evaluation of flow properties of the powder
THEORY:Evaluation of flow properties of powder are of great concern to pharmacists as several
pharmaceutical processes require free flowing powders. Such requirements include the following:

Dusting powders must be free flowing to facilitate delivery through the sifter caps
and to be evenly applied to the body.

Powder preparation such as mixing and blending will be homogenous if it has got good
flow. Poorly flowing cohesive powders are difficult to blend uniformly.

Flow behavior play critical role in fill capsules and Tablet production as it directly
effects the weight (content uniformity).

Powders that are too fluid are difficult to han d pack into capsules.
Flow properties of powders can be evaluated by measuring angle of repose or using its bulk
and tapped density (Carr’s index & Hausener ratio).
1. Angle of repose is evaluated by using flow meter or funnel and paper (variable diameter/
Petri dish (fixed diameter)
2. A quantity of powder such as Lactose is allowed to flow through a funnel, whose tip is
adjusted at 2 cm form a horizontal surface beneath, so that the apex of the heap just touch
the lower tip of the funnel.
3. Base of heap is marked / circled.
4. Height of the heap / the distance between the horizontal surface and the lower tip of the
funnel is also measured (h in mm).
5. Powder is removed and diameter d of the formed circle is measured to calculate radius r
(r = d/2)
6. Angle of repose is calculated and tabulated. angle of repose (Ø) = Tan-1 h / r
Angle of repose measurement
Observation Table:Powders
Lactose
Lactose
Lactose
Average
Height of heap (h)
Radius (r)
h/r
Relationship between angle of repose and powder flow
Angle of Repose (θ)
Flow
< 25
Excellent
25–30
Good
30–40
Passable
> 40
Poor
Angle of Repose (Ø)
Compressibility test of powders of granules
To evaluate compressibility of granules or powder, tapped density apparatus is used. Where
definite amount (100 g) or volume (250 ml) of these materials are tapped for definite time (100
times or until there is no change in the volume is occurred).
Powders
Bulk volume
(Vb)
Tapped volume
(Vt)
% Compressibility
= 100 *(Vb-Vt) / Vb
Hausener Ratio
= Vb / Vt
% Compressibility
= 100 *(ρt- ρb) / ρt
Hausener Ratio
= ρt / ρb
Lactose
Lactose
Lactose
Average
Or
Powders
Lactose
Lactose
Lactose
Average
Bulk density
(ρb)
Tapped density
(ρt)
Home Work
Discuss the importance of flow properties of powders and mention method of evaluation of flow
property.
PHT 322,382 SECTION
Experiment 7
Student Name:
Student ID:
AIM:- Preparation of effervescent granules
THEORY:-Granules are aggregations of fine powders in uniform spherical mass of about 0.2- 4
mm. These may be defined as a dosage form composed of dry aggregates of powder particles
/APIs, with or without other ingredients.
Granules are prepared by granulation which is one of the common technique of Particle size
enlargement such as Wet granulation, dry granulation, palletization, extrusion-spheronization
and slugging (A process of combining small particles into physically stronger & larger
agglomerates in order to minimize powder segregation, handling hazards and improve flow
behavior and compression of poorly flowing powders thereby improving homogeneity / content
uniformity of the materials or products (powders, tablets and capsules).
Types of Granules
Regular granules:
Granules of drug and other additives such diluents, disintegrants, glidants etc (intermediate
product in tablet manufacturing)
Coated granules:
Specialized granules containing film of polymeric material in order to control the release of the
drug after swallowing. Used in capsules dosage forms.
Effervescent granules
Specialized granules containing medicament mixed with ingredients that causes effervescence
when added to water. These usually contain mixture of acids (citric, tartaric acid) and base
(bicarbonate soda) that causes effervescence due to release of carbon dioxide. The effervescent
granules are popular in use due to the pleasant taste of carbonated solution, thus these are used
for formulation of obnoxious, bitter, bad taste APIs. These are also useful for children and elder
patients who cannot swallow tablets or capsules. Effervescent granules are frequently used as
urinary alkalizers, antacids, heartburn, flatulence etc. Therapeutic doses of API may be added in
the effervescent base. If the dose of the medicament is 0.5 g, then the finished product should
contain 4.5 of the effervescent salt mixture to each teaspoonful (5 g)
Preparation of Effervescent granules:
Effervescent base is a mixture of acid (citric acid) and alkali (sodium bicarbonate).
Tartaric acid is generally blended with citric acid as citric acid is too sticky to be manipulated.
Thus addition of tartaric acid produces a chalky friable granules.
It has been found that citric acid monohydrate and tartaric acid used in the ratio of 1:2,
respectively, produces a powder with good effervescent properties. The amount of sodium
bicarbonate to be used may be calculated from the reaction which occur when the granules come
in contact with water. The reaction equation between citric monohydrate and sodium bicarbonate
is given below: Setting up a proportion to determine the amount of sodium bicarbonate that will
react with 1 gm of citric acid or tartaric acid:
C6H8O7.H2O + 3 NaHC03 + 4 H20 = Na3C6H5O7
210
+
3C02
3 x 84
One mole of citric acid (MW = 210) reacts with 3 moles of sodium bicarbonate (MW = 84)
1/210 = X / 3 x 84
X = 1.2 g
So One gram of citric acid reacts with 1.2 g of sodium bicarbonate.
C4H606 +
150
2 NaHC03 + 2 H20 = Na2C4H4O6 + 2C02
2 x 84
One mole of Tartric acid (MW = 150) reacts with 2 moles of sodium bicarbonate (MW = 84)
1/150 = X / 2 x 84
X = 2.24 g
So One gram of Tartaric acid reacts with 1.12 g of sodium bicarbonate.
Considering a 1:2 ratio of citric acid and tartaric acid a total of 3.44 g of sodium bicarbonate (1.2
g + 1.12*2 g) will be required to react with a mixture of 3 g of acids (1 g citric acid + 2 g tartaric
acid).
Since it is desired to leave a small amount of the acids unreacted to enhance palatability and taste,
2.24 g + 1.2 g= 3.44 g, only 3.4 g of sodium bicarbonate will be utilized. Therefore, the ratio of
the effervescent ingredients is 1 : 2 : 3.4 for the citric acid : tartaric acid : sodium bicarbonate.
Rx
Ingredients
Quantities (g)
Citric acid
1
Tartaric acid
2
Sodium bicarbonate
3.4
Methods of preparation of effervescent granules
 Wet methods.
 Dry method / Fusion method
Wet Method:
1- Finely powder all of the ingredients and pass each separately, thorough sieve No. 60.
2- Mix the powder homogenously in a porcelain dish or mortar.
3-The powder mixture is massed with 95% ethanol to produce dough.
4-The dough is passed through desired sieve. Sieve No. 10 (2000 µm), Sieve No. 20 (840 µm)
5-The obtained granules are dried in hot air oven at 40 °C for 4 hours.
Dry method or Fusion Method
In the fusion method, the one molecule of water present in each molecule of citric acid acts as
the binding agent for the powder mixture.
1. Before mixing the powders, the citric acid crystals are powdered and then mixed with the
other powders of the same sieve size to ensure uniformity of the mixture.
2. Powder mixture is placed on a suitable dish in an oven at 34 to 40 °C.
3. During the heating process, an acid resistant spatula is used to turn the powder.
4. The heat releases the water of crystallization from the citric acid, which, in turn, dissolves
a portion of the powder mixture, setting the chemical reaction and consequently releasing
some carbon dioxide.
5. This causes the softened mass of powder to become somewhat spongy, and when it has
reached the proper consistency (as bread dough), it is removed from the oven.
6. Molten mass is passed through a sieve to produce granules of the desired size.
7. The granules are dried at a temperature not exceeding 50 C and are immediately placed in
containers and tightly sealed.
Home Work
Discuss the composition and application of some commercial effervescent powders.
PHT 322,382 SECTION
Experiment 8
Student Name:
Student ID:
AIM:- Capsule dosage forms filling and evaluation
Capsules are solid dosage form in which one or more medicaments are enclosed in a watersoluble, biodegradable shell made up of gelatin.
Advantages of capsules for oral administration
1. Easy to swallow due to their smooth and slippery nature
2. Easy to handle and carry.
3. Can mask the unpleasant taste, colour and odour of drug using tasteless shell.
4. Better bioavailability than tablets and faster onset of action than tablets.
5. The shells are physiologically inert and easily and quickly digested in the gastrointestinal tract.
6. The shells can be opacified (with titanium dioxide) or coloured, to give protection from light.
TYPES
HARD GELATIN CAPSULES
Hard gelatin capsule is also referred as “dry filled capsule” (D.F.C.) as their shell is hard and
consist of two sections BODY & CAP, used for filling dry materials in body capsule.
SOFT GELATIN CAPSULES
Soft gelatin capsules are a case produced from a single piece of gelatin, rather than two halves
attached together. They are used for solutions not based on water, as this would dissolve the
gelatin, but for oil based solutions. The active ingredients is dissolved in the oil-based solution,
and once the capsule is ingested, it dissolves within the body, releasing the drug. The soft gelatin
capsule is manufactured and filled using the same machine as part of a single process, and some
have the brands or dosage strength printed on then.
FILLING OF HARD GELATIN CAPSULES
1. Automatic
2. Semi-automatic
3. Manual
A hand operated gelatin capsule filling machine consists of the following parts : 1. A bed with 200-300 holes.
2. A capsule loading tray
3. A powder filling tray
4. A pin plate having 200 or 300 pins corresponding to thenumber of holes in the bed and cap
holding tray.
5. A lever handle
6. A Cam handle
7. A plate fitted with rubber top.
Size of capsules
MANUAL FILLING
1. Done by opening the capsules and dragging the body of the capsule into bulk powder.
2. Use spatula to level the filling.
3. Put the cap over body and close.
WEIGHT AND CONTENT UNIFORMITY TEST
Weight variation
Wcapsule – Wemptied shell = Wcontent
20 capsules labeled amount or average amount, ±10%
Content uniformity
The amount of active ingredient should be within the range of 85% to 115% of the label amount
for 9 of 10 capsules, with no unit outside the range of 70% to 125% of label amount.
1. Uniformity of weight: This test is to be done on 20 capsules.
Method:

Weigh an intact capsule.

Open the capsule without losing any part of the shell and remove the contents as
completely as possible. Weigh the shell.

The weight of the contents is the difference between the two weightings.

Repeat the procedure for further 19 capsules selected at random.

Determine the average weight.

Compare the average weight to the table below, to determine the % deviation permitted.

Report the results based on passing criteria
PASSING CRITERIA
Average weight of
% deviation
% deviation
capsule content (mg)
allowed
allowed
Less than 300
10 (for 18 capsules)
20 (for 2 capsules)
300 or more
7.5 (for 18 capsules)
15 (for 2 capsules)
Caps. No.
Wt. Of intact
Wt. Of the empty
capsule
shell
Wt. Of the content
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Σ=
Comparison at %
deviation
Home Work
Discuss the quality control test of capsules.
PHT 322,382 SECTION
Experiment 9
Student Name:
Student ID:
AIM:- Preparation and evaluations of tablet dosage forms
Theory:
Tablets are unit dosage form prepared by compression powdered / granulated medicine.
substances into a discoid shape by means of dies and punches.
Tablets usually consist of several materials in addition to the medicament that they deliver to
the patient. These components / tablet excipients have specific functions and names.
I- Diluents, Bulking agents, Fillers: Inert substances used to increase the volume of the
active ingredient making the handling and compression easy .
Soluble: eg Lactose, sucrose, mannitot sorbitol.
Insoluble: eg Calcium sulfate, calcium carbonate, dicalcium phosphate, tricalcium
phosphate starch
2 - Binders or Adhesives- Polysaccharides polymeric materials used to bind the powder together to
make them as cohesive paste. Binders may be added as dry powder or in solution form.
Gum Acacia / Tragacanth mucilage
Glucose syrup
Starch mucilage
Cellulose derivatives
10-20%
25-50%
5-10%
3-10%
3- Disintegratents: Materials that help tablet break up into small particles in the gastrointestinal
tract. Eg. Starch 5-10%, Modified starch (Sodium Starch Glycolate 2-5%), cellulose derivatives
(cross-linked carboxymethyl cellulose 2-4%), and Cross-linked polyvinylpyrrolidone (crosspovidone 24%).
Disintegrants are added into tablets in two portions. One half is added to the powdered components
before the wet granulation process. Second half added to the finished granulation just prior to
compression.
4-Glidants Materials that improve the flow characteristics of granulation. Example:- Talc
5-Lubricants: Materials that reduce the friction between the tablet edges and die wall during the
ejection cycle. They are usually added at the very last step before compression. They present on
the granules surfaces and in between them and the Parts of the tablet press. Magnesium stearate,
stearic acid, talc.
7-Anti- adherents: Are materials used to prevent tablet sticking to the faces of the punches
and die walls. Example: Talc.
8- Other components: These are coloring agents, flavors, sweeteners and adsorbents. etc.
AIM:- To prepare and dispense 20 tablets each containing 650 mg of sodium bicarbonate.
Sodium bicarbonate
500 mg
Acacia mucilage
q.s (25%)
Acacia powder
3%
Magnesium stearate
Talc purified.
1%
1%
Procedure
1. Acacia mucilage is prepared by dissolving 5gm of powdered acacia in 10 ml. of water and
stirring until the acacia is dissolved then complete to 20 ml warm water.
2. Sodium bicarbonate mixed with powdered acacia.
3. The pervious mixture moistened with the acacia solution.
4. Wet mass is pressed through a sieve Adding granulation liquid to make dough then passing
the dough through appropriate like Sieve No. 10 (2000 µm) or Sieve No. 20 (840 µm),
sieve Sieve No. 40 (420 µm)
5. Granules are dried at temperature not exceeding 60°C and sieved to remove powder and
small granules.
6. Granulation is transferred to the hopper of tablet machine adjusted for compression of
tablets having calculated final compression weight.
Home Work
Discuss the quality control test of the tablets..
PHT 322,382 SECTION
Experiment 10
Student Name:
Student ID:
AIM:- Evaluations of granules
Theory
Granules are evaluated in the similar manner as the powders such as flow properties by Angle
of repose, bulk density / tapped density (Carr index / Hausner ratio), moisture content etc.
Size range / size distribution of powders / granules are also very important parameter to
evaluate as it can affect the quality of the finished products (tablets or capsules). It is
evaluated by sieve analysis / Size separation, which separate particles based on their sizes
like coarse powders from fine powder by set of sieves.
Procedure for Size separation and Sieve Analysis
1. Weigh 100 gm of the dried granules or coarse powder available in laboratory.
2. Arrange the sieves on a mechanical sieve shaker with largest sieve on the top and
smallest at bottom.
3. Place the granule/ powder on the top sieve and shake for 15 minutes.
4. Weigh each fraction of the powder left on the sieves.
5. Fill the observation table
Observation table:Table: Lab measurement data for particles size analysis
Sieve Opening
Mass of granule
Retained on Each
Sieve, W (g)
% of Mass
Retained on
each Sieve
Cumulative %
Retained on the
sieve
Cumulative %
passed
Calculation
% of granule retained on the sieve
R = Mass retained on sieve / Total Mass
Cumulative % of granule retained on the sieve
Amount of granule retained in each sieve + Amount retained in the previous sieves
% of granule passed through the sieve
100 - Cumulative % of granule retained on the sieve
Home works:
Classify the size of powders / granules based on their accumulation / passage from a particular
sieve number.
PHT 322,382 SECTION
Experiment 11
Student Name:
Student ID:
AIM:- Evaluation of Tablets
Unofficial Tests : Appearance, diameter, Thickness, Hardness and Friability Test
Official Tests: weight variation, content uniformity, disintegration, dissolution.
Tablet hardness
The tablets must be hard enough to withstand mechanical stress during packaging, shipment, and
handling by the consumer. It is measured by subjecting the tablet to an increasing load along its
radial axis until the tablet breaks or fractures.
Oral tablets normally have a hardness of 4 to 8 or 10 kg; however, hypodermic and chewable
tablets are much softer (3 kg) and some sustained release tablets are much harder (10-20 kg).
Determination of Tablet Hardness using Monsanto / Pfizer / Erweka hardness tester.
Tablet Type
Hardness 1
Hardness 2
Hardness 3
Mean Hardness
Very hard tablets (due to more compression force or more amount of binder in granules ) would
fail in disintegration test.
Friability Test: Measure the ability of the tablet to withstand handling and transportation.
Friability is the tendency of tablets to powder, chip, or fragment during handling and
transportation. High friability (> 1%) affects the elegance, appearance, weight and content.
Procedure : Roche Friabilator

Take 20 tablets de-dust and weigh them (Wi)

Place tablets in friability drum , and run for to 4 min at a speed at 25 r.p.m.

Remove tablets, de dusted and re- weigh (Wf).

Note: If any tablet break in the test then batch is rejected .
Friability is expressed as a percentage loss in weight : Friability = 100 (1 - (Wi/Wf ) )
Official Standards(U.S.P.)
Weight variation test:
The weight of a tablet is determined by the depth of the die cavity, bulk density of granules or
powder, and flow behavior. Even with a proper granulation having uniform flow, a volume fill is
not as accurate as a fill based on weight. Therefore, tablet weight variations must fall within
certain specifications established by the BP or USP.
BP
80 mg or less.
80 mg to 250mg.
250mg or more.
USP
130mg or less
130mg to 324mg
More than 324mg
Limit.
10%
7.5%
5%
Weigh accurately 20 tablets individually and calculate the average weight .
Calculate the percent deviation in weight.
The tablets meet the USP test if no more than 2 tablets are outside the percentage limit and no
tablet differs by more than 2 times the percentage limit.
Uniformity of Dosage Units : Content Uniformity
Analytical determination of tablet content by UV or chemical test is required if the tablets are
potent ( 50 mg or less; 50% or less API).

30 tablets are randomly selected for the sample

At least 10 of them are assayed individually (9 of 10 tablets must contain not less than
85% or more than 115% of the labeled drug content). (10th tablet may not contain less
than 75% or more than 125% of the labeled content).

If these condition are not met, the tablets remaining from the 30 must be assayed
individually, and none may fall outside of the 85 to 115% range.
Tablet disintegration :
Disintegration is an essential attribute for tablets intended for administration by mouth , except
those intended to be chewed before being swallowed and except some types of sustained release
tablets. It is tested by observing complete disaggregation of granules / powders from the tablets.
Disintegration does not imply complete solution of the tablet or even its active constituent
.Complete disintegration is defined as that state in which any residue of the tablet remaining on
the 10 mesh screen of the test apparatus is a soft mass having no palpably firm core.
Disintegration is a (guide for an optimum tablet formula) and (as an in-process control test to
ensure lot-to-lot uniformity).
Procedure:
1.
Place one tablet in each of the six tubes of the basket , add a disk to each tube
2.
Operate the apparatus , using water maintained at (37+2) o C . as the immersion fluid
unless another fluid is specified in the individual monograph .
3.
At the end of the time limit specified in the individual monograph , left the basket from
the fluid ,and observe the tablets : all of the tablets have disintegration completely . if one or two
tablets fail to disintegrate completely , repeat the test on 12 additional tablets : not less than 16 of
the total of 18 tablets tested disintegrate completely .
Limits:
Uncoated USP tablets (disintegration time 5 min (aspirin tablets)), but majority of the tablets
have a maximum disintegration time of 30 min. ii. Enteric coated tablets are not to disintegrate
after 1 hr in simulated gastric fluid. The same tablets are then tested in simulated intestinal fluid
and are to disintegrate in 2 hrs plus the time specified in the monograph.
II)
Tablet dissolution :
The dissolution rate of the drug from the primary particles / granules of the tablet is the
important factor in drug absorption and for many formulations is the rate-limiting step.
Therefore, a dissolution time is more indicative of the availability of a drug from a tablet than the
disintegration test. Even though this is an important parameter to measure.
Place the stated volume of dissolution medium in the vessel of the apparatus specified in the
individual monograph, assemble the apparatus, equilibrate the dissolution medium to 37 + 0.5 o
C and remove the thermometer. Place one tablet in the apparatus, and operate at the specified
rate of the monograph. At the time specified, withdraw a sample and perform the analysis as in
the monograph. Repeat the test with additional tablets.
Unless otherwise specified in the individual monograph and the requirements are met if the
quantities of active ingredient dissolved from the tablets tested conform to the accompanying
acceptance table.
ACCEPTANCE TABLE
Stage
Number
S1
6
S2
6
S3
12
Tested
Acceptance Criteria
S1: Each Tablet is not less than Q + 5%
S2:Average of 12 tablets (S1+S2) is equal to or greater than Q, and no unit is less than Q-15 %
(85% of labelled claim)
S3: Average of 24 tablets (S1+S2+S3) is equal or greater than Q and not more than two tablets
are less than Q-15% (85% of labelled claim) (no tablets are less than 75% of labelled claim)
Values for t50% , t90%, and the percentage dissolved in 30 min are used as guides.
The value for t50% is the length of time required for 50% of the drug to go into solution.

Rapidly dissolving: ≥ 85% in ≤ 30 minutes

Very rapidly dissolving: ≥ 85% in ≤ 15 minutes
Home works:
Mention different types of evaluations of tablets.
PHT 322,382 SECTION
Experiment 12
Student Name:
Student ID:
AIM:- Preparation and Evaluation of suppositories.
Theory :A suppository is a solid or semisolid mass intended to be inserted into a body orifice (e.g. the
rectum, Vagina, Urethra) to provide either a local or systemic therapeutic effect. Once inserted, a
suppository either melts at body temperature or dissolves (or disintegrates) into aqueous
secretions of the cavity. Rectal suppositories are useful when oral administration is inappropriate,
as with infants, debilitated individuals, comatosed patients, and patients with nausea, vomiting
and gastrointestinal disturbances .Some drugs may cause irritation to the G.I.T. tract.
The fusion method is the principal way of making suppositories commercially and is primarily
used when cocoa butter, PEG, an d glycerin-gelatin are used as suppository bases.
Cocoa butter, (Theobroma oil) has a melting point range of 30-36°C and so readily melts in the body.
It liquefies easily on heating also sets rapidly when cooled.
Glycerol-gelatin bases are a mixture of glycerol and water stiffened with gelatin. The commonest is
Glycerol Suppositories Base BP, which has 14% w/w gelatin, and 70% w/w glycerol. In hot climates
the gelatin content can be increased to 18% w/w.
Polyethylene glycols (Macrogols) can be blended together to produce suppository bases with varying
melting points, dissolution rates and physical characteristics. Drug release depends on the base
dissolving rather than melting (the melting point is often around 50°C).
Suppositories can be prepared non-medicated as soothing or emollient, or medicated containing some
therapeutic agents.
Displacement value of medicine are amount of drugs that displaces one part of base in the molded
suppository. It depends on the density of the drugs therefore light drugs like zinc oxide have high DV
of 4.
Eg. Prepare non medicated suppository. Take average weight of 5 suppository (e.g 5 g)
Prepare 5 medicated suppository (1 g each)
with 10 % w/w of drug and 90% w/w
suppository base.
Practical weight of prepared medicated suppository is 6 g.
Base present is 90% of 6 g suppository = 5.4 g
Drug present is 10% of 6 g suppository = 0.6 g
Base displaced by 0.6g of drug = 5.4 - 5 = 0.4g
DV = 0.6 drug / 0.4 base = 6/4 = 1.5
Prepare 8 suppositories of 1 g each containing 0.3 g of drug (DV is 3).
Total amount of drugs required = 8 x 0.3 mg = 2.4 g
3 g of drug displaces 1 g of base
So 2.4 g of drug will displace = 2.4/ 3 = 0.8 g of base.
Therefore amount of base required = 8- 0.8 = 7.2 g
Procedure:
1.
Calculate and weigh the required amount of suppository base.
2.
Melt the base in china dish by putting in hot water bath.
3.
Add the powdered drug and mix thoroughly.
4.
For glycerol-gelatin base, first dissolve the gelatin by soaking in water over water bath.
5.
Add calculated amount of glycerin previously weighed in a tared crucible and
on a water bath until gelatin dissolves and a constant weight is obtained.
6.
Add the drug in cooling bases (re heat if required).
7.
Pour the hot mixture in the suppository mold.
8.
Put the mold in the fridge for 30 minutes.
Amount of ingredients (g)
Formula
Cocoa butter
C.B.
G.G.
Glycerin
Gelatin
PEG 400
PEG 4000
Water
9.7
Drug
0.3
7
1.4
1.3
0.3
PEG 1
6
3
0.7
0.3
PEG 2
3
6
0.7
0.3
PEG 3
4.5
4.5
0.6
0.3
Home works: Write down evaluation parameters of suppositories.