Ajman University of Science & Technology

Faculty Of Pharmacy & Health Sciences

.………………….

LABORATORY MANUAL FOR

DOSAGE FORM-I

Central Committee
Department of Pharmaceutics

…………………..
2000 - 2001
 Dear Students,

The central committee of department of pharmaceutics,

Faculty of Pharmacy and Health Sciences, is pleased to introduce
to you the Laboratory Manual of Dosage Forms I (700213). The
manual covers experiments deal with the principles discussed in
didactic lectures. These experiments employ fundamental
principles of pharmaceutics required to design and prepare
physically and chemically stable solid dosage forms and be
acquainted with official quality assurance methods that ensure
their therapeutic safety and efficacy. The central committee set
this manual for all the branches to ensure the uniformity of
student outcome.

Best Regards

Central Committee
Department of pharmaceutics,
Faculty of Pharmacy and Health Sciences

2
 Table of Contents

Part Content Page

No. no.
Part 1 Trituration and Aliquot
Exp.(1)  Trituration method 6
 Liquids Aliquot Method 7

Part 2 Powders
Exp. (1)  Introduction 9
 Determination of angle of repose of powders

Exp. (2) A. Preparation of Divided Powders 15

B. Preparation of Dusting powders
C. Preparation of 50g compound magnesium
trisilicate oral powder BP.
D. Preparation of oral re-hydration salts B.P.

Exp. (3) Particle Size Analysis 18

 Microscopy
 Sieving

Part 3 Granules
Exp. (1)  Introduction 25
 Preparation of Effervescent Sodium Citra tartarate
granules
Exp. (2)  Preparation of Effervescent Pot. Citra Tartarate 29
granules
Exp. (3)  Preparation of Dried dibasic sodium phosphate 30
granules
Exp. (4)  Preparation of Sulfate citra Tartarate effervescent 30
granules

Part 4 Tablets
 compressed tablet 32
Exp. (1) Preparation of 80 tablets of Aspirin using Direct 35
Compression Method

3
 Exp. (2) Preparation of 80 tablets of Aspirin U.S.P using 36
Slugging Method
Exp. (3) Preparation of 100 tablets of Chewable Antacid tablets 38
using Wet Granulation Method
 Evaluation of Tablets 39
Exp. (1) A) Unofficial tastes: 39
-Determination of tablet hardness
- Measurement of Friability
Exp. (2) B) Official standards : 44
- Determination of Weight Variation
- Determination of Content Uniformity
Exp. (3) - Tablet disintegration 47
- Tablet dissolution

Part 5 Capsules
Exp. (1)  Introduction 50
- Preparation of Ephedrine Sulfate and Phenobarbital
Capsules
Exp. (2) - Preparation of Analgesic Cachets 56
- Preparation of Atropine Sulfate Capsules
Part 6 Suppositories
Exp. (1)  Introduction 58
 Calibration of the mould (using Oily Base )
 Calculation of displacement value of solid
medication in suppositories ( using C.B. bases )
 Preparation of Iodoform suppositories
Exp. (2)  Preparation of Glycerogelatin bases ( Aqueous 64
Base )
 Calibration of Suppository Molds with
Glycerinated Gelatin Base

Exp. (3)  Preparation of suppositories using glycerogelatin 66

bases
- Preparation of Ichthammol Suppository
- Preparation of Boroglycerin Suppository
- Soap glycerin Suppositories

Exp. (4)  Macrogol Bases ( Carbowaxes Bases ) 69

-Preparation of paracetamol suppositories
APPNDIX Latin Abbreviations

4
 Part 1

Trituration and Aliquots

5
Experiment (1) :

Trituration method:

Trituration is a dilution of a potent drug powder with an inert diluent powder,

usually lactose, in a definite proportion by weight. We can then remove a weighable
portion (aliquot) of the mixture containing the desired quantity of substance to
maintain an acceptable range of accuracy.
Lactose is the most commonly used diluent in solid dosage form pharmaceuticals
such as powders, tablets and capsules. Some of the reasons included its extremely
low incidence of side effects, ready availability, and low cost.

 Preparation of absorbable dusting powder :

Rx
Corn starch 98 g
Light magnesium oxide 2g

Send 20 g
Sig. : to be used U.D.

Procedure :

1- Pulverize starch and magnesium oxide to fine powders , and pass through a
90-mesh sieve.
2- Triturate the two powders ( starch over magnesium oxide ) in a mortar with
pestle, using geometrical dilution method .

use : As lubricant for surgical gloves.

Calculation :

Because of mechanical losses during preparation , you have to calculate for

25% excess so , instead of preparing 20 g , you will prepare 25 g , the total amounts
in the prescription is 100 g , so, multiply each ingredient by a factor of (25/100).

6
Liquids Aliquot Method:

This technique is similar to the trituration method but employs liquid rather
than solid diluents. It is used only when the product to be dispensed is a liquid. A
weighable quantity of drug is dissolved in a calculated volume of a suitable solvent,
usually water or ethanol. Then, an aliquot of the solution containing the desired
amount of drug is removed.

A. Preparation of Amaranth solution using liquid Aliquot method :

Use the liquid aliquot method to prepare, label and dispense the following
prescription.

Rx
Amaranth 0.0075%
Aqua Dist. q. s ad. O. i

Sig: Put 1 tsp in baby's formula p.r.n.

Calculation :

Amaranth _____________________g (to be weighed on Rx balance)

Distilled water q.s. ______________ml (volume of solution)
Aliquot volume _________________ml
Distilled water q.s. ______________ml (to prepare final Rx product)

B. Preparation of strong sodium Salicylate mixture BPC:

Rx
Sodium Salicylate 0.5 g
Sodium metabisulfite 0.05g
Double strength chloroform water 26.25 ml
Water ad. 50 ml

Note : Because of the limitation of the prescription balance you should use Aliquot
method to accurately deliver sodium bisulfite (dissolve 0.2 g of sodium bisulfite in 4
ml of water and use 1 ml for the prescription.

7
 Part 2

Powders

8
Introduction :

The word "powder" refers to a chemical or mixture that is solid in physical

state. In compounding, "powder" refers to a dosage formulation that is solid in
physical state. But the formulation may be composed of only the active drug or may
be a mixture of the active drug and other ingredients. Powders offer some unique
advantages:

 each dose can contain a different amount of active drug

 can be administered easily to infants and young children who cannot swallow
tablets or capsules
 drug will have a rapid onset of action since disintegration is not required
 can be applied to many body cavities such as ears, nose, tooth socket, throat
 drugs tend to most stable as a solid
 can be made into many different dosage formulations (capsules, tablets,
powders for reconstitution, dusting powders, bulk powders, powders for
inhalation, etc.)

Pharmaceutical powders are formulated to be exist as fine particles. The powders

are then smooth to the touch and nonirritating to the skin. Powders generally range
from 0.1 to 10 micron in size. The size of the particles are often expressed as a
number which corresponds to the mesh screen size of a sieve. The screen size
indicates the number of openings in the mesh screen per inch. For example, a # 40
sieve has 40 openings per inch in the screen mesh. Particles that can sift through that
mesh are said to be "40 mesh" size.

Below is a list of mesh sizes and the size of the mesh opening in millimeters
(1/1000 of a meter) or microns (1/1,000,000) of a meter. Of coarse there is a
correlation between the size of the mesh opening and the particle size of the sifted
powder. As the opening becomes smaller, so will be resulting particle size. Most of
the particles of a sifted powder will have approximately the size as the mesh
opening.

9
 Mesh Opening Size
Mesh Size
millimeters microns
Number
2 9.52 9520
4 4.76 4760
8 2.38 2380
10 2.00 2000
20 0.84 840
30 0.59 590
40 0.42 420
50 0.297 297
60 0.250 250
70 0.210 210
80 0.177 177
100 0.149 149
120 0.125 125
200 0.074 74

The USP 24/NF19 uses descriptive terms to define powder fineness. The table
below shows the correlation their classification

Description Term Mesh Opening Size (microns) Mesh Size Number

Very Coarse > 1000 2 – 10
Coarse 355 -1000 20 – 40
Moderately Coarse 180 – 355 40 – 80
Fine 125 – 180 80 – 120
Very Fine 90 - 125 120 - 200

A good powder formulation has an uniform particle size distribution. If the

particle size distribution is not uniform, the powder can segregate according to the
different particle sizes which may result in inaccurate dosing or inconsistent
performance. A uniform particle size distribution insures an uniform dissolution rate
if the powder is to dissolve, an uniform sedimentation rate if the powder is used in a
suspension, and minimizes stratification when powders are stored or transported.

Reducing the particle size of a powder will result in an uniform distribution of

particle sizes. The process of reducing the particle size is called comminution. In
extemporaneous compounding, there are three methods of comminution:

10
  Trituration is the continuous rubbing or grinding of the powder in a mortar
with a pestle. This method is used when working with hard, fracturable
powders.

 Pulverization by Intervention is used with hard crystalline powders that do

not crush or triturate easily, or gummy-type substances. The first step is to use
an "intervening" solvent (such as alcohol or acetone) that will dissolve the
compound. The dissolved powder is then mixed in a mortar or spread on an
ointment slab to enhance the evaporation of the solvent. As the solvent
evaporates, the powder will recrystallize out of solution as fine particles.

 Levigation reduces the particle size by triturating it in a mortar or spatulating

it on an ointment slab or pad with a small amount of a liquid in which the
solid is not soluble. The solvent should be somewhat viscous such as mineral
oil or glycerin. This method is also used to reduce the particle size of
insoluble materials when compounding ointments and suspensions.

Classification of Powders :

 Bulk Powders:

Bulk powders are non potent and can be dosed with acceptable accuracy and
safety using measuring devices such as the teaspoon, cup, or insufflator. This
practically limits the use of orally administered bulk powders to antacids, dietary
supplements, laxatives, and a few analgesics. Many bulk powders are used topically.

 Divided Powders :

Divided powders or charts are single doses of powdered medicinal individually

wrapped in cellophane, metallic foil, or paper. The divided powder is a more
accurate dosage form than bulk powder because the patient is not involved in
measurement of the dose. Cellophane and foil-enclosed powders are better protected
from the external environment until the time of administration than paper-enclosed
powders. Divided powders are commercially available in foil, cellophane or paper
packs.
All drugs are reduced to a fine state of subdivision before weighing , the weighed
powders are blended by geometric dilution or mixing in ascending order of
amount.

 Dusting Powders :

11
 Dusting powders are fine medicinal (bulk) powders intended to be dusted on the
skin by means of sifter-top containers. A single medicinal agent may be used as a
dusting powder; however, a base is frequently used to apply a medicinal agent and to
protect the skin from irritation and friction. Bentonite, kaolin, kieselguhr,
magnesium carbonate, starch, and talc are used as inert bases for dusting powders.
Powder bases absorb secretions and exert a drying effect, which relieves congestion
and imparts a cooling sensation. All extemporaneous dusting powders should be
passed through a 100-200 mesh sieve to ensure that they are grit free and will not
further mechanically irritate traumatized areas.

 Douche Powders :

Douche powders are used to prepare solutions that cleanse the vagina. Most
douche powders are used for their hygienic effects, but a few contain antibiotics.
Douche powders are prescribed as a matter of convenience for the patient, since a
powder is more portable than a bulky solution. The formula is developed so that a
teaspoonful or tablespoonful of powder dissolved in a specified volume of water
provides the desired concentration. The pH usually ranges from 3.5 to 5 when the
solution is prepared. Feminine bulb syringes or fountain syringes are used for
vaginal irrigation. Since many of the ingredients are volatile (e.g., menthol, thymol,
and volatile oils), douche powders should be packaged in glass jars with a wide
mouth. Some commercial douche powders are available in metal foil packets, which
contain the proper amount of powder for a single douche. Many douches are also
available as prepared unit of use solutions in disposable applicators.

 Insufflations:

Insufflations are extremely fine powders to be introduced into body cavities. To

administer an insufflation, the powder is placed in the insufflator, and when the bulb
is squeezed, the air current carries the fine particles through the nozzle to the region
for which the medication is intended. All extemporaneously compounded
insufflations must be passed through a 100 mesh sieve. Pressurized packages
provide an elegant approach to the administration of insufflations.

 Powder Sprays:

In contrast to dusting powders, powders dispensed under pressure will deliver

targeted and uniform application at the desired site. Also, in an aerosol container
medicated powders may be maintained in a sterile condition. The powder particles
must be a definite size range to prevent clogging of the valve orifice and to provide

12
uniformity of application. In general, powders that are to be packaged as powder
sprays must not contain particles greater than 50 microns if they are to be sprayed
successfully.

Experiment (1)

 Determination of angle of repose of powders

In this procedure we will measure the flow characteristic of some powders of

pharmaceutical interest. And study the effect of glidents on the flow characteristics
of various powders.

Procedure :

1- A quantity of powder 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 .

2- Mark the base of heap.

3- Remove the powder .

4- Measure the diameter of the formed circle ( take the average of two diameters )

5- Repeat the process three times and calculate the average diameter (d ) , and the
radius r = d / 2 .

6- The height of the heap ( the distance between the horizontal surface and the lower
tip of the funnel is called ( h )

7- Tan the angle of repose ( Ø ) = h / r , get Ø , and tabulate your results

13
 Table (1)

Height Radius
Powder h/r Remark
(h) (r)

Sodium chloride crystalline

Lactose

2 % Talc

Aspirin

Magnesium Stearate

Sodium Alginate

Sodium chloride crystalline

+ Lactose

Sodium chloride crystalline

+ 2% Talc

Lactose + 2% Talc

14
Experiment (2)
A) Preparation of Divided Powders :

Rx
Magnesium trisilicate
Tribasic calcium phosphate
Activated charcoal aa 0.19 g

Fiat, pulv. , mitte IV

SIG.: One Chartula T.I.D. P.C.

Use : Antacid ,anti-flatulent .

Procedure:

1. Mix the ingredients to full homogeneity.

2. Divided as mentioned above (by weighing).
3. Fill in packets as follows :
a- Fold down 1 cm margin from the weighing paper .
b- Distribute the divided dose over the paper
c- left and fold the lower end of the paper until it lies exactly in the crease of
the original top fold.
d- Make additional fold.
e- Bring the two ends to each other dividing the paper to three equal parts .

B) Preparation of Dusting powders :

Rx
Camphor 0.1 g
Starch 0.6 g
Zinc Oxide 0.3 g

Send 20 G

Sig. : To be used U.D.

Use : Counter irritant.

15
Procedure:
1. Weigh the camphor and try to pulverize in the mortar with pestle.
2. Add few drops of alcohol and pulverize.
3. Mix starch and zinc oxide and gradually add to camphor while
triturating until uniformity .
4. Pass through 90-mesh sieve.

C ) Preparation of 50g compound magnesium trisilicate oral powder

B.P. :

Rx
Magnesium trisilicate 250g
Chalk, in powder 250g
Sodium bicarbonate 250g
Heavy magnesium carbonate 250g

Note : The ingredients are all active ingredients.

Procedure:

1. Mix the powders in a mortar in order of increasing bulk volume.

2. Pass the resulting mix through a 250m sieve.
3. lightly remix and pack.

Storage:
Store in a dry place, in amber glass screw capped jar or plastic pot.

Advice for patients when dispensed:

The powder should be taken mixes with a little water or other fluid between
meals, if counter prescribed prolong use should be discouraged without medical
advice.

Uses: Adsorbent and antacid for the treatment of dyspepsia.

16
D) Preparation of oral re-hydration salts BP for three separate 200ml doses of
solution. Pack the powder for each dose.

Rx sufficient for one-liter solution

Sodium chloride 10g

Potassium chloride 1.5g
Potassium bicarbonate 1.5g
Anhydrous glucose 36.4g

Note: The ingredients are all active the preparation may be flavored if required.

Procedure:
1. Make a small excess to allow for losses in the mortar.
2. Mix the powders in a mortar in order of increasing bulk pass the resulting mix
through a 250m sieve.
3. lightly remix and pack.

Storage:
Store in a dry place , supply each dose 8.80g in an individual
amber glass screw capped jar or plastic pot.

Advice for patient when dispensed:

Each dose of the powder should be dissolved in sufficient freshly boiled and
cooled water to make 200ml of solution taking hygienic precautions after
reconstitution any unused solution should be discarded after 1 hour unless
refrigerated when it may kept for 12-24 hours.

Uses: Re-hydration and electrolyte replacement in the treatment of diarrhea.

17
Experiment (3) : Particle Size Analysis

Method of Data Presentation :

1. Tables :

The most precise and general method of data presentation is the tabular
form , since the data can be expressed explicitly . The table can be a listing of
size versus one of the many ways of expressing their distribution . e.g. Size
frequency or size cumulation.

2. Graphs.

 Histograms :

A histogram is a plot of the frequency of occurrence as a function of the

size range . The ordinate , frequency , can represent no ; wt ; surface area , or
any other weighing process , in the specific size interval .

 Size Frequency Curve :

Size frequency curve is a smooth curve drawn through the mid points of
the bars of a histogram .

 Cumulative Plots :

Cumulative plots can be described as those which involve plotting the

percent of particles greater than (or less than) given particle size against the
particle size . Thus the limiting values of the ordinate vary from 0 to 100 % .
The ordinate can represent different weighing processes .

18
  Microscopy

This is the most direct method of particle size distribution measurement of

emulsions , suspensions and powders . The results are obtained on a number-
frequency bases . The projected diameter of a very large number of particles has to
be measured in order to ensure a representative count , it is useful in the size range
of 0.5 – 100 U .

Procedure :

 From the provided O/W emulsion , take 1 ml , dilute it ten times in a

measuring cylinder .
 Take one drop from the diluted emulsion , ( make sure it is too small to prevent
movement of particles ).
 Cover the slide , put it on the microscope stage , start to examine with the law
power until you get a clear field , turn to the high power and start counting .
 In every field , count all particles using roller to measure the projected
diameter of the counted particles and classify them to groups (0-2 mm , 2-4 , 4-6 ,
and so up to a larger size you find ).
 Repeat counting after changing the field , each time , so that the number of
particles measured would be about 600 particles .
 Record your results in tabular form and calculate the various statistical
diameters.
 Plot a histogram , number frequency curve , and cumulative frequency over
size of the results.

Results and Discussion :

Arithmetic mean diameter (da v) = ( nd / n ) =

2 1/2
Mean surface diameter (ds) = ( nd / n ) =
2 1/2
Standard deviation ( ) = ([ n (d- da v) ] /  n )
n= no. of particles in each group .
d= mid size od each group

Test for Homogeneity :

For the emulsion to be homogenous , 75% of the measured particles should be
in the range of (da v ± )

19
 Cumulative
Size Size
mid-size Number n Over- Over-
group group in n*d Counting
(d) (n) % Size Size
in mm microns

d% nd% d-dav (d-dav )% (n(d-dav) )%

20
Illustrated Example

Differential Distribution of Partial Sizes of Piroxicam

Part. Size dr n n% n%*(dr) n%*(dr)2 n%*(dr)3 n%*(dr)4

range (u)
1.135 - 4.54 2.8 340.0 28.1 79.7 226.1 641.4 1820.0
6.8 246.0 20.3 138.3 942.1 6415.5 43689.7
4.54 -
9.1
9.08 - 13.62 11.4 102.0 8.4 95.6 1085.0 12315.3 139778.2
13.62 - 18.16 15.9 137.0 11.3 179.8 2856.4 45388.7 721227.1
18.16 - 22.70 20.4 67.0 5.5 113.0 2309.2 47177.6 963838.2
22.70 - 31.78 27.2 110.0 9.1 247.4 6740.0 183598.8 5001231.5
31.87 - 40.86 36.4 83.0 6.9 249.2 9063.6 329598.1 11985835.6
40.86 - 49.94 45.4 42.0 3.5 157.5 7148.5 324543.3 14734267.8
94.94 - 59.02 77.0 27.0 2.2 171.6 13212.2 1017075. 78294498.7
8
59.02 - 77.18 68.1 33.0 2.7 185.6 12637.6 860619.4 58608181.2
77.18 - 95.34 86.3 17.0 1.4 121.1 10445.4 901017.3 77721754.1
95.34 - 113.50 104.4 6.0 0.5 51.7 5402.2 564102.7 58903603.3
113.50 - 122.6 1.0 0.1 10.1 1240.8 152094.9 18643795.3
131.66
Sum 1211.0 100.0 1800.7 73309.2 4444589. 325763520.7

Smarmy of Mean Diameter Parameters for Piroxicam

Arithmetic Mean Diameter, dav =[  (n%*(dr))/100] =17.46 µ

Mean Surface diameter, ds =[  (n%*(dr))2/100] = 25.8 µ

Mean Volume diameter, dv = [  (n%*(dr))3/100] = 33.6 µ

[  (n%*(dr))3]
Mean Volume Surface diameter, dsv = _______________ =56.77 µ
[  (n%*(dr))2]

[  (n%*(dr))4]
Mean Weigh diameter, dw = _______________ = 7.05 µ

[  (n%*(dr))3]

21
22
n%
Frequency (n%)

0
5
10
15
20
25
30

0.0
5.0
10.0
15.0
20.0
25.0
30.0
1.135 - 4.54

0.0
4.54 - 9.08
9.08 - 13.62
13.62 - 18.16
18.16 - 22.70

50.0
22.70 - 31.78
31.87 - 40.86
Histogram

40.86 - 49.94

Mid. Size
94.94 - 59.02

100.0
Partical Size Range (u)
59.02 - 77.18
77.18 - 95.34
95.34 - 113.50

Size Frequency Curve

113.50 - 131.66

150.0
  Sieving

This is the simplest and most widely used method of determining particle size
distribution . Results are obtained on weight basis , it useful to a practical lower limit
of 76 µ .

Procedure :

Weigh accurately about 100 gm . of the supplied powder , place on the top
sieve of the stack of sieves , cover and shake for 10 minutes . Weigh the remaining
powder on each sieve . Tabulate your results and calculate d av.

Plot the weight distribution curve and the cumulative undersize curve of the
results .

Average particle size (dav) =  [ ( % retained ) x ( Mean screen opening )]/100

Cumulative%
Screen- Mean
Weight %Weight
opening Screen Weight-size
Retained Retained Over- Over-
opening
Size Size

23
 Part 3

Granules

24
Granulation

Granules are particles ranging in size from about 4 to 10 mesh. Granules

generally are made by first blending the powders together and then moistening the
mixture to form a pasty mass. The mass is passed through a sieve and then dried in
air or in an oven. They are prepared as a convenience for packaging, as a more stable
product due to less surface exposure, and as a popular dosage form. Granulation are
also used as intermediates in the preparation of capsules and tablets, since they flow
more smoothly and predictably than do small powder particles.
The most popular compounded granulation is the effervescent powder
(sometimes called effervescent salts). These granulation are popular due to their
taste and psychological impression. When added to water, the granulation
effervesces ("fizzes") as carbon dioxide is liberated.

Preparation of Effervescent Granulation

It has been found that citric acid mono hydrate and tartaric acid used in the
ratio of 1:2, respectively, produces a powder with good effervescent properties.
Citric acid mono hydrate is not used alone because it results in a sticky mixture that
will not easily granulate. Tartaric acid is not used alone because the granules are too
friable and crumble. 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 mono hydrate 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, one has:

25
Similar calculations show that 2.24 gm of sodium bicarbonate react with 2 gm of
tartaric acid

Thus, with the acids in a ratio of 1:2, it has been calculated that 3.44 g (1.2 g +
2.24 g) of sodium bicarbonate is necessary to react stoichiometrically with the 3 g of
combined acids. To enhance the flavor, the amount of sodium bicarbonate may be
reduced to 3.4 gm to allow for a small amount of unreacted acid to provide a tart
taste.
The ratio of two acids should be adjusted as excess tartaric acid will lead to
tough mass , while excess of citric acid will lead to soft mass .

The liberated carbon dioxide has the following advantages :

- It masks the bitter and nauseous taste.

- It promotes gastric secretions.
- It acts as a carminative.

Aim of Granulation:

To slow the violent effervescence which could happen if preparation is in the

powder form.

26
 Methods of preparation :

There are two methods of preparation of granules :

1- Dry fusion method
2- Wet method

1- Fusion method

In the fusion , the one molecule of water present in each molecule of citric
acid acts as the binding agent for the powder mixture . After weighing the
required amount of powders they are mixed together to ensure the uniformity of the
mixture. Then the powder is placed on a porcelain dish on boiling water bath and
stirred with the help of a glass rod . The heat causes the release of the water of
crystallization from the citric acid which in turn dissolves a portion of the powder
mixture, setting of the chemical reaction and the consequent release of some carbon
dioxide. This causes the softened mass of powder to become somewhat spongy, and
when of the proper consistency as bread dough ,it is removed from the oven and
rubbed through an acid resistant sieve to produce granules are dried at temperature
not more than 54 – 60 o C and transferred to containers which are then promptly and
tightly sealed . The fused method is used in the preparation of most commercial
effervescent powder .

2- Preparation of granules using Wet Method :

1- All powders are dried to constant wt. At temp. 100-105 o C.

2- Pulverize each powder through sieve No.90 weigh the calculated amount
separately.
3- Pass the pulverized powder through sieve No. 90 and weigh the calculated
amount from each powder separately .
4- Mix the powder together and by the aid of alcohol 96 % ( drop adding ) make the
mass coherent between your fingers and the mixing is continued until the mass
will retain its shape when molded into a ball .
5- The mass is forced through sieve No. 10 then dry in ovens at temp. not exceeding
50 o C .
6- After drying the granules sieved through sieve No. 20 to leave the fine particles,
and packed in well closed wide mouth bottles.

Calculation :

Calculate for slight excess due to the mechanical loss ( loss from handling the
materials and during the preparation ) and the chemical loss (loss from liberation of
CO2 & H2O , the chemical loss nearly equals to 1/7 formula).

27
Experiment 1:

 Preparation of Effervescent Sodium Citra tartarate granules

Prepare 25 g of effervescent sodium citra tartarate ( B.P.C.) having the following

formula :
Rx

Sodium bicarbonate 510 g

Tartaric acid 270 g
Citric acid 180 g
Sucrose 150 g

1110 g

use : digestive ,carminative

These amounts of the ingredient base will give 1000 g only , thus 110 g
which is lost due to liberated CO2 & H2O ( chemical loss).

calculation:

mechanical loss ( lies between 15-20% ) , so,

for mechanical loss we take ( 25 x 20 /100 + 25 )
= (5+25) = 30 g. from the base.

for NaHCO3 (30 x 510)/1000 =15.3 g

Tartaric (30 x 270)/1000 = 8.1 g
Citric acid (30 x 180)/1000 =5.4g
Sucrose (30 x 150)/1000 = 4.5 g

33.3 g. Total

Thus 33.3 g is the total amount of ingredient after adding the amounts which
can loose during handling and during chemical reactions.

28
If the amount of sodium bicarbonate is not known , calculate it as follows :

( amount of citric acid x Eq. wt. Of sod.bicarb.)

Amount of Sod. Bicarbonate = +
Eq. wt. Of citric acid

( amount of tartaric acid x Eq. wt. Of sod.bicarb.)

Eq. wt. Of tartaric acid

= ( (180 x 84)/70 + (180 x 84)/75 ) = 519.4 g.

In the prescription the amount used is 510 g ,so the final solution will be
slightly acidic.

Experiment 2:

 Preparation of Effervescent Pot. Citra Tartarate granules

Prepare 25 g of effervescent pot. citra tartarate having the following formula

Rx
Pot. citrate 200 g.
Tartaric acid 477 g.
Citric acid 252 g.
Sucrose 150 g.

Sig. : Coch . parv. T.I.D. p.c.

use : Systemic and urinary alkalizer.

29
Experiment 3 :

 Preparation of Dried dibasic sodium phosphate granules

Prepare 25 g of effervescent Dried dibasic sodium phosphate having the

following formula

Rx
Dried dibasic sodium phosphate 200g
Sodium bicarbonate 477g
Tartaric acid 252g
Citric acid monohydrate 162g

Sig. : Coch . parv. T.I.D. p.c.

use : digestive ,carminative

Experiment 4:

 Preparation of Sulfate citra Tartarate effervescent granules

Prepare 25 g of effervescent Sulfate having the following formula :

Rx

Magnesium sulfate 200 g

Sod .bicarbonate 500 g
Tartaric acid 240 g
Citric acid 210 g

Sig.: Coch . parv. T.I.D. p.c.

Doses :

16 g as cathartic.
2.5 g as mild Laxative .

30
 Part 4

Tablets

31
 Compressed Tablets
Introduction :
The compressed tablet is one of the most popular dosage forms today. About
one-half of all prescriptions dispensed are for tablets. Usually one considers a
compressed tablet as an oral medication; however, tablets have many other uses. The
sublingual tablet, the pellet, the wafer, the troche, and the vaginal insert are
manufactured by the same procedure as an oral tablet.
Tablets contains certain excipients selected to aid the processing and improve
the properties of the product .

Tablet Excipients :
1) Fillers : used to increase the bulk of the tablet . it is generally not feasible to
make tablets with a weight of loss than about 70 mg. It is essential that fillers be
inert and stable .
A - Soluble : lactose , sucrose , mannitol , sorbitol .
B – Insoluble: calcium sulfate , dicalcium phosphate , tricalcium
phosphate , starch , calcium carbonate .
2) Binders : the substance that glue powders together and cause them to form
granules are the binders or adhesives. They are either sugars or polymeric
materials.
Examples
- Water .
- Ethanol ,
- Acacia mucilage (10-20%) and it gives hard ,friable granules ,
-Tragacanth mucilage (10-20%) ,
- Gelatin solutions (2-10%) , they are strong sdhesive ,use warm.
-Starch mucilage (5-10 %) , one of the best general adhesieves ,use warm.
- Glucose syrup (25-50%) , strongly adhesive , tablet may soften in high
humidity
- PVP (3-15%)

32
- Cellulose derivative (5-10 %)

3) Lubricants ,glidents and anti – adherents :

Three of the problems associated with tablet manufacture are the flow of granulation
, the adhesion of material to the punches and dies , and release of the tablet from the
press.
- Lubricants :
Are those agents that the friction between the tablet edge and die wall during
the ejection cycle . e.g. magnesium stearate - Lubricants are usually added at the
very last step before compression , since they must be present on the surfaces of the
granules between them and the parts of the tablet press .
- Glidants :
Are materials that improve the flow characteristics of granulation e.g. talc.
- Anti – adherents :
Function to prevent tablet granulation from sticking to faces of the punches and
the die walls e.g. talc .
4) Disintegrants :
Is a term applied to substance added to a tablet granulation for the purpose of
causing the compressed tablet to break apart when placed into an aqueous
environment .
Method of adding disintegrant :
It is better to add it in two portions , one half is added to the powdered
components before the wet granulation process and the remaining portion is added to
the finished granulation just prior to the compression . This method hold that a
disintegrent is required between the granules as well as within them Some of the
commonly used disintegrant
- Starch (5-20% w/w )
- Avicel (5-20 % w/w)
- Algenic acid (5-10 %w/w)
- Veegum (5-15 % w/w)

33
- Bentonite ( 5-15 % w/w)

Single-punch Tablet Machines

Tableting machines are commonly used in pharmaceutical industry. They are
high-speed machines that create thousands of tablets in a small period. The
compounding pharmacist uses a variation of these machines. It is called a single-
punch tablet press and makes one tablet at a time. A "punch" has two pieces of
castled tubular metal. The bottom metal piece has a small cavity in one end of the
tube; the top metal piece has one end that is tapered into a small rod that will just fit
into the small cavity in the other piece. The rod does not go all the way to the bottom
of the cavity, but leaves a small gap. The punch is fitted into a press so that when the
handle is depressed and released, the rod goes into and then comes out of the bottom
piece. To make a tablet, the powder material is placed into the bottom piece, and the
handle is depressed and released. The powders are compressed and occupy the size
of the gap designed in the punch.
Punches come in many sizes which allows the production of tablets of
different sizes and compression strengths. But each punch is a matched set; it is not
possible to interchange the top and bottom pieces of different punches.
Chewable tablets, effervescent tablets, and compressed tablets can be made
using a tablet press. Chewable tablets are generally made using mannitol because it
has a sweet, cooling taste and is easy to manipulate. Other ingredients may include
binders (e.g., acacia), lubricants (e.g., stearic acid), colors, and flavors. The powder
mixture is prepared, the desired quantity of mixture is weighed, and then pressed
with a single-punch tablet machine.

34
Experiments :
There are three methods of commercially making compressed tablets:
1) The Direct Compression Method :
A compressible vehicle is blended with the medicinal agent, and if necessary,
with a lubricant and a disintegrant, and then the blend is compressed. Substances
that are commonly used as directly compressible vehicles are: anhydrous lactose,
dicalcium phosphate (Emcompress), granulated mannitol, microcrystalline cellulose
(Avicel), compressible sugar (Di-Pac), starch (Sta-Rx 1500), hydrolyzed starch
(Celutab), and a blend of sugar, invert sugar, starch and magnesium stearate (Nutab).
Experiment 1 :
 Preparation of 80 tablets of Aspirin using Direct Compression Method
Prepare 80 tablets of Aspirin each containing 325 mg.

Ingredient Composition Quantity Quantity

per per 100
tab.(mg) tab. (g)
Aspirin (granular) (mesh 40) 90% 325 32.5
Starch (Disintegrant) 7% 25 2.5
Talc (Glident ) 2.4% 9 0.9
Srearic acid 0.6% 2 0.2
Total Tablet Weight 361

Procedure :
1. Screen aspirin on 40 mesh sieve to remove the fine particles.
2. Blend all the ingredients in a mortar using plastic spatula.
3. Compress into tablets using 9 mm standard concave punches.

35
2) The Dry Granulation Method (Slugging Method) :
The ingredients in the formulation are intimately mixed and precompressed on
heavy duty tablet machines. The slug which is formed is ground to a uniform size
and compressed into the finished tablet.
However, when direct compression is not possible due to the properties and
those of the drug ,and wet granulation cannot be used because the drug is sensitive
to moisture and heat, then dry granulation remains the only method available.

Experiment 2 :
 Preparation of 80 tablets of Aspirin U.S.P using Slugging Method :
Prepare 80 tablets of aspirin U.S.P. (fine)

Ingredient Composition Quantity Quantity

per per 100
tab.(mg) tab. (g)
Aspirin (fine powder) 90% 325 32.5
Starch (Disintegrant) 7% 25 2.5
Talc (Glident ) 2.4% 9 0.9
Srearic acid (lubricant) 0.6% 2 0.2
Total Tablet Weight 361
Procedure :
1. Mix all the above ingredients (except) 50 % of starch, talk and
magnesium stearate.
2. Compress into slug using 18 mm flat face punishes.
3. Grind the slugs using 20 mesh screen.
4. Transfer into cubic mixture and the reminder disintegrant and lubricant, mix
for 10 minutes.
5. Compress to weight using 9 mm concave punishes.

36
 3) The Wet Granulation Method :
This method has more operational manipulations, and is more time-consuming
than the other methods.
The wet granulation method is not suitable for drugs which are thermo labile or
hydrolysable by the presence of water in the liquid binder. The general steps
involved in a wet granulation process are:
 The powdered ingredients are weighed and mixed intimately by
geometric dilution.
 The granulating solution or binder is prepared.
 The powders and the granulation solution are kneaded to proper
consistency.
 The wet mass is forced through a screen or wet granulator.
 The granules are dried in an oven or a fluidized bed dryer.
 The dried granules are screened to a suitable size for
compression.
 A lubricant and a disintegrating agent are mixed with the
granulation.
 The granulation is compressed into the finished tablet.

37
 Experiment 3 :
 Preparation of 100 tablets of Chewable Antacid tablets using
Wet Granulation Method :
Prepare 100 Chewable antacid tablets .

Ingredient Quantity per Quantity per

tab.(mg) 100 tab. (g)
Aluminum Hydroxide 300 30
Calcium Carbonate 150 15
Mannitol 100 10
Gelatin ( as 10%solution) 20
Magnesium Stearate 15
Talc 15
Oil of Peppermint 0.2
Total Tablet Weight 600

Procedure:
1. Mix the first three ingredients and moisten with a 10 % gelatin solution until
formation of coherent mass.
2. Granulate by passing through 10 mesh screen.

3. Dry at 50o C. Overnight, screen the drug granules through 20/35 mesh.
4. Add the oil of peppermint mixed with talc and finally the magnesium stearate.
5. Mix for 5 minutes in a cubic mixer.
6. Compress using 12 mm flat face punishes.

38
 Evaluation of Tablets
Tablets are evaluated by a variety of methods.

A) Unofficial Tests :
1.Tablet hardness
The tablets must be hard enough to withstand mechanical stress during
packaging, shipment, and handling by the consumer. Section <1216> of the USP
24/NF19 outlines a standard tablet friability test applicable to manufactured tablets.
Most compounding pharmacy would not have the apparatus specified in Section
<1216>. However, there are several hand operated tablet hardness testers that might
be useful. Examples of devices are the Strong Cobb, Pfizer, and Stokes hardness
testers. The principle of measurement involves subjecting the tablet to an increasing
load until the tablet breaks or fractures. The load is applied along the radial axis of
the tablet. 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).

Experiment 1 :

 Determination of Tablet Hardness

Using a hardness tester ( Erweka ) , determine the hardness of the four (4)
different types of tablets supplied. Use an average of three measurements for each
determination and comment on your results.

39
Hardness Tester _______________
Tablet Mean
Hardness 1 Hardness 2 Hardness 3
Type Hardness

Comment on Results :

2. Friability Test:
 Measurement of Friability : This test is designed to measure the ability of
the tablet to withstand handling and transportation.

40
Procedure : ( using Roche Friabilator ) :
1. Take 20 tablets dedust and weigh them (wo)
2. Place tablets in friability drum , switch on the apparatus adjusting the timer to 4
min. , and the speed at 25 r.p.m.
3. At the end of the operation the tablets are removed , de dusted and re- weighed
(w) . should any tablet break the batch is rejected .
4. Friability B is expressed as a percentage loss in weight :
B =100 (1 - (w/wo ) )
5. If value of B is 1.0 % or less , the batch is accepted .

41
B) Official Standards(U.S.P.)
I ) Uniformity of Dosage Units :
Analytical determination of tablet content:
This probably will not be done due to the requirement of specialized
equipment. However, the weight variation of the tablets can be measured by
weighing each individual tablets and determining the percent difference from the
intended amount. Guidelines in the USP 24/NF19 Supplement 1 indicate that each
tablet "shall be not less than 90% and not more than 110% of the theoretically
calculated weight for each unit."

Experiment 2 :
 Determination of Weight Variation:
The total weight of a tablet is determined by the depth of the die cavity, bulk
density of granules or powder, and uniformity of particulate flow. 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 USP.
Tablets are required to meet a weight variation test where the active ingredient
comprises a major portion of the tablet , tablets containing 50 mg or less of active
ingredients , comprising less than 50% by weight of the tablet should pass a content
uniformity test.
Procedure :
Select 30 tablets and proceeds as follows ;
1) Weigh accurately 10 tablets individually and calculate the average weight .
2) Calculate the average value of drug content as % following the assay procedure
using another sample obtained from the same batch .
3) Calculate the relative standard deviation (RSD)
[ Note : use excel program ]

42
 Tablet Weight of Tablet % Labeled
# (mg) Claim
1
2
3
4
5
6
7
8
9
10
Note: Labeled claim is 750 mg
 Mean (as % of labeled claim) _________
 Standard Deviation __________
 RSD __________

( Assay procedure of Aspirin tablets : )

Powder 10 tablets , weigh 0.5 g of powdered tablets , put in conical flask , add 25 ml
of 0.5 N NaOH , boil gently for 5 min. , cool and titrate excess alkaline with 0.5 N
HCL using phenol red as indicator
- Each ml of 0.5 N HCL is equivalent to 0.045 g Aspirin
- Repeat the operation without aspirin
- Amount of Aspirin = ( B – Exp. ) x 0.045 = A
- % of Aspirin in tab. =( A / 0.5 ) x 100
(average content )
4) Calculate the content of active ingredient
in each 10 tablets = tab. Wt. X average content
100

43
 Determination of Content Uniformity:
NOTE: Tablets should be analyzed in the same order as the weight variation
test so that a comparison between weight variation and content uniformity can
be made.
Determine the content of active ingredient of the tablets by the procedure given
below.
- Select 30 tabs and proceed as follows :
- Assay 10 tablets individually as directed in the assay in the individual monograph
unless otherwise specified in the test for content uniformity
- Calculate RSD as before.

Criteria : ( apply the following criteria , unless otherwise specified in the

individual monograph )

A) If the average of the limits specified in the potency definition in the individual
monograph is 100 % or less :
For weight variation , or content uniformity :
The requirements are met if the amount of the active ingredient in each of 10
tablets tested lies within the range of 85 % to 115 % of the label claim and relative
standard deviation is less than or equal to 6.0% .
If one tablet is outside the range of 85% to 115 % of the label claim and no
tablet is outside the range of75 % to 125 % of the label claim or if RSD is greater
than 6 , or if both conditions prevail , test 20 additional units the requirements are
met if not more than one tablet of the 30 is outside the range of85 % to 115 % if the
label claim and no tablet is outside the range of 75 % to 125 % of the label claim and
RSD of the 30 tablets does not exceed 7.8 % .

44
B) If the average of the limits specified in the potency definition in the individual
monograph is greater than 100 % :
1. If the average value of the tablets tested is 100 % or less , The requirements are
as in (A) .
2. If the average value of the tablets tested is greater than or equal to the average of
the limits specified in the potency definition in the individual monograph , the
requirements are as in (A) . except that the word s “ label claim “ are replaced by
the words “label claim multiplied by the average of the limits specified in the
potency definition in the individual monograph is divided by 100 “ .
If the average value of the tablets tested is between 100 % and the average of the
limits specified in the potency definition in the individual monograph , the
requirements are as in (A) , except that the word s “ label claim “ are replaced by the
words “label claim multiplied by the average value of the tablet tested ( expressed as
% of label claim ) divided by 100 “

45
Experiment 3 :
I) Tablet 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.
Disintegration (for un-coated tablets )
This test is provided to determine compliance with limits on disintegration stated
in the individual monograph . 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 screen of the test apparatus is a soft mass having no palpably firm
core.

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 .
Apparatus : refer to USP for details.

46
II) Tablet dissolution :
Disintegration time determination is a useful tool for production control, but
disintegration of a tablet does not imply that the drug has dissolved. A tablet can
have a rapid disintegration time yet be biologically unavailable. The dissolution rate
of the drug from the primary particles 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 Acceptance Criteria
Tested
S1 6 Each Tablet is not less than Q + 5%
S2 6 Average of 12 tablets (S1+S2) is equal to or
greater than Q, and no unit is less than Q-15 %
S3 12
Average of 24 tablets (S1+S2+S3) is equal or
greater than Q and not more than two tablets are
less than Q-15%

Continue testing through the three stages unless the results conform at either
S1 or S2. The quantity Q, is the amount of dissolved active ingredient specified in
monograph expressed as a percentage of the labeled content. Both the 5% and 15%
value in the acceptance table are percentages of the labeled content.
Dissolution Test For Aspirin Tablets (Uncoated)
- Medium : 0.05 M acetate buffer having pH of 4.5; 500ml
- Time : 30 min , Q : 75 %

47
Assay Procedure :
1) At the time specified, 2 ml aliquot is pipetted out through a Millipore filtration
unit and placed in a 50 ml volumetric flask. Then add 2 ml dissolution medium to
the dissolution vessel.
2) After adjusting volume to 50 ml with 0.1N sulfuric acid, the absorbance of each
solution is measured at 228 nm.
3) The amount of Aspirin dissolved ( C ) =
(Absorbance X Conc. Factor X Dil. Factor X Dissolution Medium Volume) =
(Absorbance X 0.02 X 25 X 500 ) mg.
4) Percentage of Aspirin dissolved at time specified =
5) C/ Label Claim X 100 = C/325 X 100

Dissolution Apparatus :

48
 Part 5

Capsules

49
Introduction:

Capsules are gelatin shells filled with the ingredients that make up an
individual dose. Dry powders, semi-solids, and liquids that do not dissolve gelatin
may be encapsulated. Capsules account for about 20% of all prescriptions dispensed.
Capsules have several advantages as pharmaceutical dosage forms:

1. They may be used to mask the unpleasant tastes, aromas, or appearance of a drug.
2. They allow powders to be dispensed in an uncompressed form, thus allowing for
quicker dissolution and absorption of the drug following oral dosing (as compared
with tablets).
3. They offer the pharmacist versatility to prepare any dose desired for a variety of
administration routes (e.g. oral, inhalation, rectal, or to be diluted for vaginal, rectal,
oral or topical use).
4. They may be easier than tablets for some people to swallow.
5. They can be make to alter the release rate of the drug.

Their disadvantages or limitations include the following:

 They are easily tampered with (although techniques exist for preventing this).
 They are subject to the effects of relative humidity and to microbial
contamination.
 They may be difficult for some people to swallow.
 More expensive (commercially).

Hard Gelatin Capsules:

The hard gelatin capsule consists of a base or body and a shorter cap, which
fits firmly over the base of the capsule. For human use, eight sizes of capsules are
available. The capacity of each size varies according to the combination of drugs and
their apparent densities. Capsules are available as clear gelatin capsules or in a

variety of colors. The pharmacist can use the different colored capsules to
distinguish two capsule formulations for the same patient, or to encapsulate
unattractive ingredients.
The pharmacist can add a dye to the powder before filling a clear capsule to
impart a color for identification or esthetics.

50
 Some types of hard gelatin capsules have a locking cap, which makes it more
difficult to reopen the capsule.

To aid in the selection of the appropriate size, a table, with the capacity of five
common drugs for that particular size capsule, is printed on the box of the capsules.
As a guide, the relative sizes and fill capacities of capsules are given below. By
knowing the bulk density of fill material, proper choice of capsule size is usually
made easier; however, trial and error soon develops the judgment of the beginning
pharmacist.

Capsule Size Volume ( ml) Mg of Lactose Mg of Aspirin

000 1.37 1340 1000
00 0.95 929 600
0 0.68 665 500
1 0.50 489 300
2 0.37 362 250
3 0.30 293 200
4 0.20 195 125
5 0.13 127 60

 "Punch" Method

To hand fill capsules at the prescription counter, the pharmacist generally uses the
"punch" method. The ingredients are triturated to the same particle size and then
mixed by geometric dilution. The powder is placed on a powder paper or ointment
slab and smoothed with a spatula to a height approximately half the length of the
capsule body. The base of the capsule is held vertically and the open end is
repeatedly pushed or "punched" into the powder until the capsule is filled; the cap is
then replaced to close the capsule. Each filled capsule is weighed using an empty
capsule as a counterweight. Powder is added or removed until the correct weight has
been placed in the capsule. The filled capsule is tapped so that no air spaces are
visible within the contents.

It is a good practice to remove from the stock container the exact number of
empty capsules needed before you begin filling them. In this way you avoid
preparing the wrong number of capsules and at the same time avoid contaminating
the empty capsules with drug particles that cling to your hands. Also, since some fill
material will likely be lost in the process of punching capsules, the pharmacist
generally calculates for the preparation of at least one extra capsule to insure enough
fill for the last capsule.

51
 The simplest method by which a capsule may be kept free of moisture during
compounding is to wash the hands well, dry them, and keep the fingers dry by
stripping a towel through the cleansed fingers until warmth is felt. An alternative
method is to use the base of one capsule as a holder for other bases during the filling
operation. The capsules do not come in contact with the fingers. The most sure
method of protecting the capsule is to wear finger cots or rubber gloves.

Capsule Machines

Capsule machines are available for filling 50, 100, and 300 capsules at a time.
Each manufacturer's machine is slightly different in its operation, but the series of
operations is the same. Capsules are first loaded into the machine. Most machines
come with a capsule loader which correctly aligns all of the capsules in the machine
base. There are plates on the machine base that can be adjusted. First, the plates are
adjusted to hold the capsule bodies in place while the caps are removed all at one
time. The caps remain in place in the top of the machine for later use. Then the
plates are adjusted again so that the capsule bodies will "drop" into place so that the
tops are flush with the working surface of the plate.

The formulation powder is poured onto the plate and special spreaders and
combs are used to fill the individual capsules. Some manufacturer's have special
shakers that will also help spread the powder and fill the capsules. The powder is
spread evenly over the plate, and the comb is used to tamp and pack the powder into
the capsules. These two processes are repeated over and over again until the capsule
bodies are filled with the powder. All of the caps are then simultaneously returned to
the capsule bodies, and the closed capsules are removed from the machine.

The machine has the advantage of filling many capsules in a timely manner.
However, there is a tendency to pack the capsules in the middle of the plate with
more powder than the capsules along the periphery. It takes practice to ensure that
each capsule has the same amount of drug. A quality control procedure should be
executed with each batch of capsules produced with the machine.

52
Final Processing

Once the capsules have been compounded and the capsule closed, the
pharmacist may want to "seal" the capsule. The best way is to use "locking"
capsules, where the body and cap lock together, making it very difficult to open the
capsule again. If using locking capsules, during the filling process the cap is not
completely closed onto the body in the weighing procedure to determine the weight
of powder in the capsule. The locking is done only one time and that is after the
capsule is correctly filled.
If locking capsules are not used, a seal can be made by touching the outer edge of
the body with a moist towel to soften the gelatin. Alternatively, a cotton swab dipped
in warm water can be rubbed around the inner edge of the cap. When the cap is
closed on the body, it is slightly twisted to form the seal.

When compounding and sealing are complete, the capsules may need cleaning
to remove fingerprints, traces of body oils, or loss powder from the capsule.
Fingerprints and oils cannot be effectively cleaned from capsules so the best way to
prevent these problems is to wear gloves during the compounding process. Any
clinging powder can be removed by rolling the capsules between the folds of a
towel.

Another proposed cleaning method is to put the capsules in a container filled

with sodium bicarbonate, sugar, or sodium chloride, and gently roll the container.
Then the container contents can be poured into a ten-mesh sieve where the "cleaning
salt" will pass through the sieve.

Capsules should be visually inspected and checked for:

 Uniformity - check capsules for uniformity in appearance and color.
 extent of fill - check capsules for uniformity of extent of fill to ensure that all
capsules have been filled.
 locked - check capsules to ensure that they have all been tightly closed and
locked.

Additional Considerations :

Capsules are made of gelatin, sugar, and water and contain about 10% to 15%
moisture. Gelatin can absorb up to ten times its weight in water. So if gelatin
capsules are placed in areas of high humidity, they will become malformed or miss
happened as they absorb moisture. On the other hand, if capsules are placed in low
humidity, they become dry and brittle and may crack.

53
 To protect capsules from the extremes of humidity, they should be dispensed
in plastic or glass vials and stored in a cool, drug place. It appears that a storage
relative humidity of 30% to 45% is best. Cotton can be placed in the top of the vial
to keep the capsules from rattling.

If powders that are being mixed before encapsulation are very light and fluffy
and "difficult to manage," add a few drops of alcohol, water, or mineral oil. As an
alternative, mix these powders in a plastic bag. If the powders seem to have a "static
charge," use about 1% sodium lauryl sulfate.

Magnesium stearate (less than 1%) can be added to powders to increase their
"flow ability" which makes filling capsules easier. However, magnesium stearate is a
hydrophobic compound and may interfere with the dissolution of the powders.

Experiment ( 1) :
 Preparation of Ephedrine Sulfate and Phenobarbital Capsules

Rx
Ephedrine Sulfate 0.025 g.

Phenobarbital 0.015 g.

Make 6 capsules
Sig.: one cap. q.i.d.

Use : treatment of bronchial asthma

Procedure :

1- The powders are triturated intimately and mixed by geometric dilution

2- The resting powder is placed on a powder paper and smoothed with a spatula to a
height approximately half the length of capsule body.
3- The open end of the capsule base is repeatedly pushed into the powder until the
capsule is filled
4- The cap. is then placed back to close the capsule .

54
5- Each filled capsule is weighed using empty capsule as counterpoise, powder is
added or removed until the correct weight is obtained .
6- Finally the capsule is cleaned to remove any trace of powder trapped on the
surface

Calculation:

Calculate for 10 capsules using no. 0 capsules

1. Fill one capsule with lactose in previously described manner and determine the
exact capacity of capsule by weighing suppose it is 0.5 g.

2. Calculate the amounts drugs for 10 capsules and substrate from total amount of
lactose (0.5 g x 10 ) to get amount of lactose which you will use e.g. ( 0.5 g x 10
– (0.025 x 10 + 0.015 x 10 ) ) = 4.6 g lactose

3. Weigh the calculated amounts of lactose ( 4.6 g ) , ephedrine sulfate (0.25 g ) and
Phenobarbital ( 0.15 g ) .

Experiment (2) :

 Preparation of Analgesic Cachets :

Rx
Codeine phosphate 0.06 g
Aspirin 0.25 g
Acetophenetidine 0.12 g
Caffeine 0.12 g

Make 6 Cachets
Sig: 1-2 p.r.n. to relieve pain .

Procedure : Prepare in the manner described .

Use : Analgesic .

55
Experiment (3) :

 Preparation of Atropine Sulfate Capsules :

Rx
Atropine sulfate 0.4 mg
Lactose Q.S.

Make 6 Capsules
Sig: one cap. t.i.d.

Procedure : Prepare in the manner described using aliquot dilution method .

Use : Antispasmodic .

Aliquot Dilution Method :

1. Determine the exact capacity of the given capsule No. 2,using lactose
e.g. it is 0.4 g
2. Calculate No. of dilutions you need = 0.4g/0.4mg =1000 times .
3. Do dilution in two steps (25x40 times ).
4. Weigh 120 mg of atropine sulfate , and dilute it 25 times by lactose on glass slab
{120 mg x 25 = 3.0 g {i.e. 120 mg atropine sulfate + 2.88 g of lactose .)]
5. From this diluted amount , take 150 mg , and dilute it 40 times by lactose
(150mgx40 ) = 6 g (i.e. 150 mg from the mixture +5.85g lactose)then form this
blend fill capsules to 0.4 g as shown .

56
 Part 6

Suppositories

57
Introduction :

Suppositories are medicated, solid bodies of various sizes and shapes suitable
for Introduction into body cavities. The medicament is incorporated into a base such
as cocoa butter which melts at body temperature, or into one such as glycerinated
gelatin or PEG which slowly dissolves in the mucous secretions. Suppositories are
suited particularly for producing local action, but may also be used to produce a
systemic effect or to exert a mechanical effect to facilitate emptying the lower
bowel.
The ideal suppository base should be nontoxic, nonirritating, inert, compatible
with medicaments, and easily formed by compression or molding. It should also
dissolve or disintegrate in the presence of mucous secretions or melt at body
temperature to allow for the release of the medication. As with the ointment bases,
suppository base composition plays an important role in both the rate and extent of
release of medications.

Methods of preparation :
Suppositories can be extemporaneously prepared by one of three methods :
1. Hand Rolling is the oldest and simplest method of suppository preparation and
may be used when only a few suppositories are to be prepared in a cocoa butter base.
It has the advantage of avoiding the necessity of heating the cocoa butter. A plastic-
like mass is prepared by triturating grated cocoa butter and active ingredients in a
mortar. The mass is formed into a ball in the palm of the hands, then rolled into a
uniform cylinder with a large spatula or small flat board on a pill tile. The cylinder is
then cut into the appropriate number of pieces which are rolled on one end to
produce a conical shape.
Effective hand rolling requires considerable practice and skill. The suppository
"pipe" or cylinder tends to crack or hollow in the center, especially when the mass is
insufficiently kneaded and softened.

2. Compression Molding is a method of preparing suppositories from a mixed mass

of grated suppository base and medicaments which is forced into a special
compression mold. The method requires that the capacity of the molds first be
determined by compressing a small amount of the base into the dies and weighing
the finished suppositories. When active ingredients are added, it is necessary to omit
a portion of the suppository base, based on the density factors of the active
ingredients.

3. Fusion Molding involves first melting the suppository base, and then dispersing
or dissolving the drug in the melted base. The mixture is removed from the heat and
poured into a suppository mold. When the mixture has congealed, the suppositories

58
are removed from the mold. The fusion method can be used with all types of
suppositories and must be used with most of them.

Suppository Bases :
Suppository bases may be conveniently classified as according to their
composition and physical properties:
 Oleaginous (fatty) bases
 Water soluble or miscible bases (hydrophilic)

1. Oleaginous Bases include Theobroma Oil and synthetic triglyceride mixtures.

Theobroma Oil or cocoa butter is used as a suppository base because, in

large measure, it fulfills the requirements of an ideal base. At ordinary room
temperatures of 15° to 25°C (59° to 77°F), it is a hard, amorphous solid, but at 30° to
35°C (86° to 95°F), i.e., at body temperature, it melts to a bland, nonirritating oil.
Thus in warm climates, theobroma oil suppositories should be refrigerated.

Particular attention must be given to two factors when preparing suppositories

with cocoa butter base. First, this base must not be heated above 35°C (95°F)
because cocoa butter is a polymorphic compound and if overheated will convert to a
meta stable structure that melts in the 25° to 30°C (77° to 86°F) range. Thus, the
finished suppositories would melt at room temperature and not be usable.
The second factor is the change in melting point caused by adding certain drugs
to cocoa butter suppositories. For example, chloral hydrate and phenol tend to lower
the melting point. It may be necessary to add spermaceti or beeswax to raise the
melting point of finished suppositories back to the desired range.

The newer synthetic triglycerides consist of hydrogenated vegetable oils. Their

advantage over cocoa butter is that they do not exhibit polymorphism. They are,
however, more expensive. Some of the bases are single entity formulations. Some of
the names may denote a series of bases. In a series, the bases are varied to give a
range of melting points. For example, Fattibase® is a single entity base that consists
of triglycerides from palm, palm kernel, and coconut oils.

2. Water Soluble/Water Miscible Bases are those containing glycerinated gelatin

or the polyethylene glycol (PEG) polymers.

Glycerinated Gelatin is a useful suppository base, particularly for vaginal

suppositories. It is suitable for use with a wide range of medicaments including
alkaloids, boric acid, and zinc oxide. Glycerinated gelatin suppositories are
translucent, resilient, gelatinous solids that tend to dissolve or disperse slowly in
mucous secretions to provide prolonged release of active ingredients.

59
 Suppositories made with glycerinated gelatin must be kept in well-closed
containers in a cool place since they will absorb and dissolve in atmospheric
moisture. In addition, those intended for extended shelf-life should have a
preservative added, such as methylparaben or propylparaben, or a suitable
combination of the two. To facilitate administration, glycerinated gelatin
suppositories should be dipped in water just before use.

Standardization of suppositories :
The Standardization of any supp. Involves the following determinations:
a- Determination of DISPLACEMENT VALUE of the active ingredients
b- Determination of FRACTURE POINT of the prepared supp. ( the weight under
which the supp. Sample collapses under given conditions is taken as a measure of
the strength of the supp. Tested .
c- determination of MELTING TIME of the prepared suppository .
d- determination of UNIFORMITY OF WEIGHT of the prepared suppository .

1) Lubrication of moulds :

Lubrication the cavities of the mould is helpful in preventing adhesion of

supp. To the mould .The lubricant must be different in nature from the suppository
mass otherwise it will become adsorbed, and fail to provide a film between the mass
and the metal. Consequently an oily lubricant is unless for coca butter base but used
in glycerogelatin base e.g. liquid paraffin, olive oil and almond oil .
For C.B. base and another fatty bases we must use alcoholic lubricants as soap
liniment .

Having the following formula , lubricate your mould :

Rx
Soft soap 1 part
Glycerin 1 part
Alcohol (90%) 5 parts

60
 Experiment (1) : ( Oily base )

I) Calibration of the mould :

To determine the exact capacity of the mould by using cocoa butter .

Procedure :

1) Make sure that the two halves of the suppository mould given to you having the
same number .
2) Lubricate the mould with soap solution by mean of cotton piece , invert the
mould on a porcelain slab to allow the excess of lubricating solution to drain .
3) Wt. an amount of C.B. ( 5 g if you are supplied with a mould of one gram
capacity and 10 g if you are supplied with a mould of two gram capacity ) to
prepare 3 suppositories ( there is a slight excess for mechanical loss ) and melt it
in a porcelain by exposing the crucible for new seconds to steam of a water bath
, remove the crucible away from steam and triturate with a glass rod , repeat until
a uniform cream , which is easily poured, is formed .
4) Pour gradually in a continuos stream the melted C.B. into the lubricated mould
and allow the melted mass to overfill to avoid the formation of holes after cooling
(due to contraction of the mass ).
5) Cool the filled mass for about 10 min. , and after cooling remove the excess C.B.
by sharp knife.
6) Wt. accurately certain number of suppositories and then calculate the average wt.
7) Calculate the correction factor (C.F.) = average weight /nominal capacity
( written on the mould )

61
II) Calculation of displacement value of solid medication in suppositories
( using C.B. bases ) :

Displacement value :

“ is the amount of medicament which displaces one part of C. Butter “.

If medicament you are going to incorporate in C.B. base has density of
approximately that of C.B. , the weight of medication may replace an equal weight
of the oil . If , however , the medication is heavier , it will replace a proportionally
smaller amount of C.B. (i.e.) Displacement value is 1.6 ). If the suppositories were to
carry 0.1 g each , a dozen would require 12 g . This is divided by 1.6 , (D.V. of the
tannic avid ) , which indicates that 1.2 g of tannic acid will replace only 0.85 g of
C.B (1.2/1.6 ) , not 1.2 g and proportionally more base must be taken to provide
sufficient diluents for 12 supp.

Procedure :

1) Prepare and weigh 3 suppositories of theobrome oil = a .

2) Prepare and weigh 3 suppositories containing say 10 % of medicament = b .
3) Calculate the amount of theobrome oil in the medicated supp.
4) Oil of theobrome = b x 90 /100 = c
5) Medicament = b x 10 / 100 = d
6) Calculate the amount of cocoa butter displaced by the medicament a-c .
D.V. = wt. of medicament / wt of C.B. displaced by the medicament = d / (a-c )
Calculate the displacement value of these medicaments Z no , Bisub gallate , Boric
acid , iodoform , Lead Acetate , Tannic acid using the procedure given above and the
medicaments in a % of 10 % .

N.B. :
 The incorporation of each medicament – just after melting the base add
the pulverized and sifted medicament stir carefully until a uniform and
homogenous mass is formed the pour into a lubricated mould .
 Avoid overheating during melting the base .
 Displacement value of liquid medicaments equal to ONE .

62
III) Preparation of Iodoform suppositories :

Prepare 3 supp. Of C.B. containing 0.1 g Idoform ( D.V. of Iodoform = 4 ).

N.B. : for calculations :

 Calculate for 2 excess C i.e. if we want to prepare 3 supp. Calculate for 5 .
 Put in your mind the D.V. of the added medicaments .
 generally the amount of base is calculated in the following manner : wt. of
base = [ ( No. of supp. X mould capacity ) – ( No. of supp. X wt of medicament /
D.V. ) ] C.F.
= [ 5 X 1 – ( ( 5 X 0.1 ) / 4 ) C.F.

63
Experiment (2) : ( Aqueous bases )

I) Preparation of Glycerogelatin bases :

There are many formulas of glycerogelatin bases , the U.S.P. formula is :
Rx
Gelatin 20g
Glycerin 70g
Water to 100g
B.P.
C.F.

Procedure :

1) In a porcelain dish soak the gelatin powder with amount of H2O present in the
formula for about 5 – 10 min. till it completely wetted and swelled
2) add the amount of glycerin to the soaked gelatin.
3) Put the dish on boiling water bath .
4) Stir gently till complete solubility of gelatin and the formulation of a translucent
mass, avoid air bubbles formation during stirring
5) Pour the translucent mass into mould (previously lubricated with liquid paraffin
or any other oil ) after adding the medicament (if the formula containing
medicament ) and – Take care that preferably JUST FILL the cavities because the
mass does not contract upon cooling .

N.B:

 Gelatin base is incompatible with many of the substances prescribed in

supp. E.g. Tannic acid , Ferric chloride , Gallic acid , and for this another
reasons this base is less frequently use than coca butter .

 Glycerin supp. Containing Ichthammol became insoluble on storage

 Gelatoglycerin bases used mainly for preparing supp. Containing boric

acid , chloral hydrate , ichthamol , iodine (dissolved by the aid of KI )

64
II) Calibration of moulds:
 Calibration of Suppository Molds with Glycerinated Gelatin Base
Glycerinated Gelatin Suppositories have the following proportions of glycerin,
gelatin, and water. Use 25 g of the suppository base for this calibration exercise.

Percentag Weight Amt./Vol. to

Ingredients
e Basis measure
Glycerin 70% __________ g _________ ml
Gelatin 20% __________ g _________ g
Purified Water 10% __________ g _________ ml

To calibrate the mold with glycerinated gelatin suppository base:


Clean mold with soap and water.

Dry the mold.

Have the mold at room temperature.

Lubricate the mold with light mineral oil.

Mix the glycerin and water together and heat on a steam bath or hot plate for 5
minutes. Gently stir in the gelatin to avoid incorporating air in the mixture.
After the gelatin has been added, continue heating for another 40 - 50 minutes.
Do not allow the temperature to get above 90 - 95°C, as the color will darken.
 Remove from the heat and allow the mixture to cool near the melting point
before pouring into the mold.
 Overfill the cavities in the mold, cool at room temperature for 30 minutes, and
then place in a refrigerator 15-20 minutes if the suppositories have not
completely congealed.
 Carefully remove excess with a hot spatula or knife. Remove suppositories
from mold.
 Using only perfect specimens, weigh the suppositories and record the total
weight. Calculate the average suppository weight.
Calculate the correction factor (C.F.) = average weight /nominal capacity

Mold # __________
Total weight for ____ suppositories = _________ g
Average weight for one suppository = _________ g
Correction Factor (C.F.) = _________
Mold lubricant used _____________________
Inspection of Final Product _____________________

65
III) Preparation of suppositories using glycerogelatin bases :

Prepare the following prescriptions:

 Ichthammol Suppository

Rx

Ichthammol 1g
Glycerogelatin base Q.S. 4g

Ft. Peccaries Mitte III

Calculation:

- Calculate for 5 peccaries (2 excess )

- Wt. Of Ichthammol = 5 x 1 = 5 g
- Wt. Of Glycerogelatin base =

[ No. of supp. X mould capacity –( ( No. of supp. X wt. Of active ingredient ) /

D.V. )]

= 5 x 4 - ( ( 5 x 1) / D.V. ) C.F.
= (20 – 5 ) x C.F (either 1.15 or 1.2 according to the formula used)
= 15 x C.F

Then the amount of gelatin , glycerin , H2O can be calculated from the base formula.

After calculation follow the general method of preparation given above taking into
consideration that Ichthammol must be added after formation of translucent mass
and avoid air bubbles formation .

66
  Boroglycerin Suppository

Rx

Boric acid 7.5 g

Gelatin 15.0 g
Glycerin 62.5 g
Water 15.0 g

Fiat supp. Mitte III

Calculation :-

- The formula gives 100 g of suppository mass.

- To prepare 3 supp. Calculate for 5 .
- If we use mould of 1 g capacity the amounts are as follows :

Boric acid = (1 x 5 x 7.5 ) / 100 = 0.375 g

Gelatin = (1 x 5 x 15 ) / 100 = 0.750 g
Glycerin = ( 1 x 5 x 62.5 ) / 100 = 3.125 g
Water = (1 x 5 x 15 ) / 100 = 0.750 g

-If we use mould of 2 g capacity the amounts given above multiplied by (2) and so
on.

Procedure :

1) In a porcelain dish soak gelatin in water , then transfer to dish over a water bath .

2) Dissolve boric acid in glycerin by the aid of gentle heat .

3) Add the dissolved boric acid the gelatin solution and continue heating over a
water bath until a clear solution produced and constant wt is attained .

N.B.

- Boric acid reacts with glycerin on heating giving glycerol borate which has
an antiseptic action .

67
IV) Soap glycerin Suppositories :

Stearin soap ( i.e. cured soap , sodium stearate ) has certain advantages over gelatin
for making glycerin sufficiently hard for suppositories .

a- A large quantity of glycerin can be incorporated actually up to 95 % of the mass.

b- Soap assists the action of the glycerin , whereas gelatin does not .

The disadvantage is that soap glycerin suppositories are very hygroscopic and
require to be wrapped in waxed paper or pure tin foil and protected from the
atmosphere . The soap is used formed in glycerin solution by interaction between
sodium carbonate and stearic acid .

Rx

Glycerin 90 g
Sodium carbonate ( Cryst.) 2.5 g
Stearic acid 7.5 g

Fiat supp. Mitte III

Procedure :

1) Dissolve the sodium carbonate in the glycerin with the aid of gently heat .
2) Add the stearic acid and heat carefully until effervescence ceases and solution is
complete . ( clear solution )
3) Skim the surface and pour the solution when it is quite hot and free from bubbles
( make sure no bubbles interrupt in solution before pouring it )
4) Overfill the mould , because considerable contraction occurs and trim level when
set .

N.B. :

The process may be hastened by heating the mixture over a benzene burner
until the reaction starts , then transferring the dish to water bath .

Use : for rectal use , as laxative .

68
 Experiment (3) : Macrogol Bases ( Carbowaxes Bases )

Carbowaxes ( polyethylene glycols ) are polymers of ethylene oxide and have

different molecular wt. ranging from 200 to 20,000 . At room temperature the lower
members of the series are liquid , P.E.G. 1000 and 1540 are soft solid and the higher
members are wax like . They melt between 37 o C – 36 o C .

Advantages :

1) Easily shaped into smooth and acceptable suppository

2) Dissolve in H2O forming transparent solution and soluble in mucous membrane

secretion .

3) Do not hydrolyze or deteriorate .

4) Do not support mould growth .

5) Do not produce irritation of the mucous membrane .

6) Inert , compatible with most drugs .

7) Supp. Are prepared by fusion method . Macrogol bases are not altered by
overheating ( C.F. from C.B. bases )

8) They do not adhere to the mould which needs no lubrication .

Disadvantages :

1) On standing supp. Develops fracture . P.E.G. are soluble in water to the extent of
about 60 % the inclusion of 20 % water will produce a super saturated system
during the fusion process , the system undergoes slow crystallization or
granulation which causes fracture in the suppository .

2) Incompatible with phenol and reduce the antiseptic effect of quaternary

ammonium compounds .

The following mixture of polyethylene glycols of varying hardness have been

described for use as suppository bases

69
 1 Macrogol (4000) 33%
Macrogol (6000 ) 47%
Water 20 %
2 Macrogol (1540 ) 33 %
Macrogol ( 6000 ) 47 %
Macrogol ( 400 ) 20 %
3 Macrogol ( 1540 ) 33 %
Macrogol ( 6000 ) 47 %
Water 20 %
4 Macrogol ( 1000 ) 96 %
Macrogol ( 4000 ) 4%
5 Macrogol (1000 ) 75 %
Macrogol ( 4000 ) 25 %

 Preparation of paracetamol suppositories

Rx

Paracetamol 200 mg
Caorbowax Q.S. 2.0 g
Cabowax bases :
Macrogol 1000 75%
Macrogol 4000 25%

Fiat supp. Mitte III

SIG.: one supp. P.r.n.

Calculations:
- C.F. of the base formula used = 1.1
- D.V. of paracetamol = 2.0

Procedure :

1) Weigh amounts of P.E.G. and melt in a porcelain dish on boiling water bath .
2) Make sure that the mould is dry , and warm it at about 50 o C .
3) Dispense the amount of drug in the melted base , and pour in the warmed mould (
no need for lubrication ) .
4) Allow to congeal for 5 min. , and transfer to fridge , if needed.

Use : Antipyretic .

70