PHT 261 Practical Students Hand out

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King Saud University
College of Pharmacy
Department of Pharmaceutics
FLOW PROPERTIES OF POWDERS
The flow property of a material results from many forces that can act
between the solid particles, such as: the frictional forces, surface tension forces,
mechanical forces caused by interlocking of particles of irregular shapes, and
cohesive or Vander Waals forces.
Importance:
1. The ability of powder to flow is one of the important factors involved in
mixing different materials to form a powder blend. Mixing is an important
pharmaceutical operation involved in the preparation of many dosage
forms, including tablets and capsules, and in the studying of dusting
powders.
2. The internal flow and granule demixing (the tendency of the powder to
separate into layers of different sizes), during flow through the hopper
contribute to a decrease in tablet weight during the latter portion of the
compression period.
3. The flow rate of a tablet granulation increase with an increase in the
quantity of fines added to the granulation. Also, an increase in the lubricant
added will raise the flow rate.
Factors affecting the flow properties of powders:
 Particle size: smaller particles have bad flow because the cohesive forces
between the particles are of the same magnitude as gravitational force. So,
as particle size increases, the flow is facilitated (improved).
 Shape of the particles: flat or elongated particles tend to pack. So, round
shape particles are better.
1
 Porosity and density: particles with a high density and low internal porosity
tend to possess free-flowing properties.
 Texture: surface roughness can lead to poor flow properties due to friction
and cohesiveness.
 To improve flow characteristics of powders, materials termed GLIDANTS
are frequently added to granular powders.
 Glidant: is a material that improves the flow properties of granulations by
reducing the interparticulate friction and eliminating the problems
associated with the flow of materials.
 Examples of commonly used glidants include: magnesium stearate (0.22%), starch (2-5%), and talc (0.3-1%).
 Two of the most common methods to determine the flow properties of
powders are:
1. angle of repose method, and
2. Hopper flow rate measurements.
DTERMINATION OF ANGLE OF REPOSE OF POWDERS
(sodium chloride, lactose, and lactose +2 % talc)
Angle of repose: is the maximum angle
between the surface of a pile of powder
and the horizontal plane.
tan θ = h / r (h: the height, r: the radius)
then, θ = tan -1 h / r
As θ decreases, the flow property increased.
2
Procedure:
1. A quantity of the supplied powder is allowed to flow carefully through
a funnel, whose tip is adjusted at 2 cm
from a horizontal surface beneath (see the
diagram), so that the apex of the heap just
touch the lower tip of the funnel.
2. Mark the base of heap. Then remove the
powder.
3. Measure the diameter of the formed circle (take the average of two
diameters).
4. Repeat the process three times and calculate the average diameter (d).
And the radius (r = d / 2).
5. The height of the heap (the distance between the horizontal surface and
the lower tip of the funnel) is called (h).
6. Tan the angle of repose θ (tan θ = h / r), get θ (θ = tan -1 h / r), and
tabulate your results.
7. Comment on the results.
Results:
Tabulate the results as shown in the table:
powder
Height (h)
Radius (r)
Sodium chloride
(crystalline)
Lactose
Lactose + 2 %
talc
Comment on the results
3
Angle of repose (Θ)
PARTICLE SIZE ANALYSIS
 Clinically, the particle size of a drug can affect its release from dosage
forms that are administered orally, parenterally, rectally, and topically.
 The successful formulation of suspensions, emulsions, and tablets also
depends on the particle size achieved in the product.
 In the area of tablets and capsules manufacture, control of the particle size
is essential in: Achieving the necessary flow properties, and proper
mixing of granules and powders.
Methods of particle size analysis:
Sieving method:
This method is the simplest and most widely used method of determining
particle size and size distribution.
Results are obtained on weight basis.
This method utilizes a series of standard sieves calibrated by the National
Bureau of Standards.
According to the method of USP, a definite mass of the sample is placed on
the proper sieve in a mechanical shaker. The powder is shaken for a
definite period of time, and the material that passes through one sieve
and is retained on the next finer sieve is collected and weighed.
Optical microscopy method:
Sedimentation method:
Methods of data presentation:
1. Tables:
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 the weight, surface area, or
any other weighing process, in the specific size interval.
Size frequency curve:
This is a smooth curve drawn through the mid points of the bars of a
histogram.
4
Cumulative plots:
Cumulative plots can be described as those which involve plotting the
percent of particles greater than (or less than) a 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.
DETERMINATION OF PARTICLE SIZE BY SIEVING METHOD
Procedure:
1. Weigh accurately 100 g of the supplied powder, then place on the top
sieve of the stack of sieves, cover and shake (mechanically) for 15
minutes.
2. Weigh the remaining powder on each sieve.
3. Tabulate your results.
4. Plot the required curves (histogram, normal distribution curve, and
cumulative curves).
Table of results:
Sieve
diameter
(particle
size), mm
Mean
particle
size (mm)
Weight
retained
on the
sieve (g)
%weight
Cumulative %
retained
(frequency)
Σ=
5
Under-size
Over-size
Graphs:
Using graph papers, plot the following:
Histogram. (frequency vs. the particle size range)
Size distribution curve. (frequency vs. the mean particle size)
Cumulative curves. (% cumulative vs. the mean particle size)
Problem: Particle size analysis by sieving method
A sample of granules having different particle size was analyzed
utilizing a series of standard sieves placed in a mechanical shaker. The sample
is shaken for a definite period of time, and the material that passes through one
sieve and retained on the next finer sieve was collected and weighed.
The following data were obtained:
Particle size
range
Weight
retained on the
finer sieve (g)
1.25-1.00 mm
10.35
1.00mm-800μm
14.50
800-710μm
23.71
710-600 μm
32.62
600-500 μm
45.61
500-400 μm
30.21
400-315 μm
21.62
315-250 μm
13.92
250-125 μm
7.40
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EFFERVESCENT GRANULES
 The effervescent granules are preparations for oral administration of salty
bitter drugs. Also, they form a pleasant method for the administration of
saline substances.
 The effervescent granules are composed of: sodium bicarbonate, citric acid,
tartaric acid, and sometimes sugar (to overcome the nauseous taste) in
addition to the medicament and the granulating agent (ethanol 96%).
 They are taken by dissolving the directed quantity in water and drinking
whilst in state of effervescence.
 The amounts of acids (citric acid and tartaric acid) are used in slight excess
over the neutralization of sodium bicarbonate, so the final solution becomes
slightly acidic for more pleasant taste.
 The equation of the reaction:
CH2COOH
CH2COONa
3 NaHCO3 + HO-C-COOH . H2O
4 H2O +3 CO2 + HO-C-
COONa
CH2COOH
CH2COONa
 The liberated carbon dioxide has the following advantages:
a. It masks the bitter and nauseous taste.
b. It promotes gastric secretions.
c. It acts as a carminative.
d. It has psychological impression at the patient.
 For the medicament:
a. Solid medicaments must be dried at 100-105 oC for constant weight to
liberate any water of crystallization which can interfere with the partial
interaction, giving rise to dead granules.
b. liquid medicaments, as extracts, require special treatment:
 Aqueous extracts (e.g., liquid extract of liquorice) must be
concentrated to a soft mass.
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 Alcoholic extracts (e.g., tincture of belladonna) are used as
the granulating agent, and alcohol 96% is then added if the
amount of the extract is not enough for granulation.
c. Some drugs like iron ammonium citrate and potassium iodide
need special treatments (e.g., the use of a glass mortar).
 Methods of the preparation of the granules:
1. Wet method:
 This method is used in hot countries due to the ability of liberation of
water of crystallization from citric acid.
 Suitable for heat sensitive materials.
 Alcohol is used as the granulating agent (its water content enhances
the interaction between alkali and the acids).
 Steps:
All powders are dried to a constant weight at a temp. 100-105 oC.
Pulverize each powder separately.
Pass the pulverized powder through sieve No. 90, and weigh the
calculated amount from each powder separately.
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 retains its shape when molded into a ball.
The mass is forced through sieve No. 10, then dry in oven at temp. not
exceeding 50 oC.
After drying, the granules are sieved through sieved No. 20 to leave the
fine particles, and then packed in well closed wide mouth bottles.
2. Dry method (fusion method):
This is based on the release of water of crystallization from citric acid by
the aid of heat using a boiling water bath.
Steps:
Finely powder all of the ingredients and pass each, separately, through
sieve 90.
8
Mix the powders homogenously in a porcelain dish and raise over a
boiling water bath.
The mixture of the powders is continuously triturated, while on water
bath. When the mass adjacent to heat seems doughy, turn over so as to
allow for the release of all water of crystallization of citric acid.
The point, at which the mass seems doughy, is considered critical. At such
time, the dish is removed from heat and the dough is quickly forced
through sieve No. 10. The collected granules are dried in a hot air oven
at 40 oC.
The dried granules are shaked gently over a sieve (No. 20) and the nonpassed granules are collected for packing.
 Packaging and storage of the effervescent granules:
a. The granules should be packed in wide mouth bottles (to permit the
entering of the teaspoon).
b. Bottles are covered with wax or paraffin film to prevent the
absorption of moisture from the atmosphere.
c. Store in cool, dry place.
Practical example # 1:
Prepare 25 g of sodium sulfate effervescent granules containing 5% liquid
extract of hyoscyamus :
Rx
Sodium sulfate
*F
500 g
Sodium bicarbonate 500 g
Tartaric acid
240 g
Citric acid
210 g
N.B., sodium sulfate loses 50% of its weight on drying.
Sig. : MDS.
9
Calculations:
1. Add 20% excess to the required amount to compensate for the
mechanical loss (loss arised from handling the materials and
during the preparation) and the chemical loss (arised from
liberation of CO2 & H2O, the chemical loss is nearly equals to 1/7
of the formula).
So, the total weight =
2. Weight of sod. Sulfate =
3. Amount of hyosyamus extract =
4. amount of base =
5. F =
base
=
totalRx
Procedure:
1. Weigh the required amount of each ingredient.
2. Powder each ingredient alone (in mortar with pestle) to a very fine
powder.
3. Mix the powders geometrically in a mortar using the pestle.
4. Add hyoscyamus extract and triturate with the pestle to form the wet
mass which can be pressed against the sieve. (If the amount of the
extract is not enough to form the paste, add alcohol 96% (drop adding),
gradually, to make a wet mass that retains its shape on handling).
5. Screen the wet mass formed on mesh-12 sieve to get the granules.
6. Leave the granules to dry, (open air drying if the humidity is low), or
dry in an oven at a temp. not exceeding 50oC.
7. Pack the granules in a well – closed, wide mouth bottle. Fix a white
label.
Label:
White
10
Use:
Sodium sulfate is used as a saline laxative to prompt watery evacuation of the
bowel (in the treatment of constipation). While, hyoscyamus extract is an
antispasmodic.
Practical example # 2:
Prepare 25 g of sodium phosphate effervescent granules containing 5% iron
ammonium citrate :
Rx
*F
sodium phosphate
500 g
Sodium bicarbonate 500 g
Tartaric acid
240 g
Citric acid
210 g
N.B., sodium phosphate loses 60% of its weight on drying.
Sig. : MDS.
Calculations:
1. Add 20% excess to the required amount to compensate for the
mechanical loss (loss arises from handling the materials and
during the preparation) and the chemical loss (arises from
liberation of CO2 & H2O, the chemical loss is nearly equals to 1/7
of the formula).
So, the total weight =
2. Weight of sod. Phosphate =
3. Amount of iron ammonium citrate =
4. amount of base =
5. F =
base
=
totalRx
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Procedure:
1. Weigh the required amount of each ingredient.
2. Powder each ingredient alone (in mortar with pestle) to a very fine
powder.
3. Powder iron ammonium citrate (in a glass mortar with pestle) to a very
fine powder.
4. Mix the powders geometrically in a mortar using the pestle.
5. Add alcohol 96% (drop adding), gradually, to make a wet mass that
retains its shape on handling.
6. Screen the wet mass formed on mesh-12 sieve to get the granules.
7. Leave the granules to dry, (open air drying if the humidity is low), or
dry in an oven at a temp. not exceeding 50oC.
8. Pack the granules in a well – closed, wide mouth bottle. Fix a white
label.
Label:
White
Use:
Sodium phosphate is used as a saline laxative, while iron ammonium citrate is
used in the treatment of iron deficiency anemia.
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EVALUATION OF CAPSULE DOSAGE FORMS (B.P)
1. disintegration test:
 The disintegration test determines whether tablets or capsules
disintegrate within a prescribed time when placed in an aqueous medium
under the prescribed experimental conditions.
 Disintegration is the state in which no residue, except fragments of
capsule shell, remains on the screen of the test apparatus or adheres to
the lower surface of the disc, if a disc has been used.
 Method:
1. Introduce one capsule into each tube and suspend the apparatus in the
beaker containing water.
2. If the hard capsule floats on the top of water, the disc may be added.
3. Operate the apparatus. Record the time. Remove the assembly from the
liquid. The capsules pass the test if no residue remains on the screen of
the apparatus.
4. The capsules should disintegrate within 30 minutes, unless otherwise
justified.
2. uniformity of weight:
 This test is to be done on 20 capsules.
 Method:
1. Weigh an intact capsule.
2. Open the capsule without losing any part of the shell and remove the
contents as completely as possible. Weigh the shell.
3. The weight of the contents is the difference between the two weightings.
4. Repeat the procedure for further 19 capsules selected at random.
5. Determine the average weight.
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6. Compare the average weight to the table below, to determine the %
deviation permitted.
7. Calculate the upper and lower limits at the % deviation stated, and at
double that percentage.
8. Compare the individual weights of the capsule contents to the upper and
lower limits calculated at the % deviation stated, and at double that %.
9. Limit: not more than two capsules of the individual weights deviate
from the average weight by more than the % deviation listed in the table,
and none deviates by more than twice that %.
Table:
Average weight of
% deviation
capsule content (mg)
Less than 300
10
300 or more
7.5
Results of disintegration test:
 Time recorded for the capsules to break into particles and pass to the
liquid medium = ----------------- minutes.
 Comment:
Results of weight variation test:
 Average weight of the contents = (total wt. of the contents / 20) =
 % deviation permitted (from the table) =
 Upper limit (at % deviation) = av. Wt. + (%/100 x av.wt.)
=
 Lower limit (at % deviation) = av. Wt. - (%/100 x av.wt.)
=
 Upper limit (at double % deviation)
av.wt.)
14
= av. Wt. + (double%/100 x
=
 Lower limit (at double % deviation)
= av. Wt. - (double%/100 x
av.wt.)
=
Caps.
No.
Wt. Of
Wt. Of the
intact
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=
 comment:
15
Comparison Comparison
at %
deviation
at double %
deviation
SUPPOSITORY DOSAGE FORMS
 Suppositories are defined as solid products of various weights and shapes
intended for introduction into the rectum, vagina or urethra where they
melt, dissolve or disperse and exert a local or systemic effect.
Characteristics of an ideal suppository base:
1. It should melt, dissolve or disperse at 37 oC.
2. Non- irritant, and non-toxic.
3. Physically stable during manufacture or storage.
4. Convenient to handle by the patient and does not break or melt on
handling.
5. Does not leak from the rectum or vagina.
6. Compatible and chemically stable with drugs.
Types of suppository bases:
1. oleaginous bases:
Cocoa butter and Cocoa butter substitutes.
2. water – soluble bases:
Polyethylene glycol mixture and Glycerinated gelatin
3. water dispersible bases:
Polyethylene glycol derivatives, and Cocoa butter substitutes (with
surfactants), e.g., Witepsol, Massa estranium, Massupol.
Methods of preparation:
1. Hand rolling method:
2. compression method:
3. fusion method:
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Lubrication of moulds:
1. Lubrication of the cavities of the mould is helpful to prevent the
adhesion of the suppository to the sides of the mould.
2. the lubricant must be:
 different in nature from the base otherwise it will become absorbed,
and fail to provide a film between the mass and the metal (i.e., it
should be immiscible with the base) , and
 Compatible with the drugs and any other additives.
Consequently, an oily lubricant is useless for CB base but used in
glycerogelatin base, e.g., liquid paraffin, olive oil and almond oil, and for CB
base and other fatty bases we must use an alcoholic lubricant as soap liniment.
Containers and special labeling instructions:
The prepared suppositories should be wrapped individually in metal
foil (or waxed paper, if the medicament interacts with metal).
Glass or plastic screw-capped jars are suitable containers for products
that are hygroscopic.
Commercially prepared suppositories are supplied in strips of sealed
semi-rigid moulds prepared from polyvinyl alcohol.
Special labels:
Store in a cool place.
For rectal use only.
For vaginal use only.
Calibration of the mould:
Calibration of the mould is carried out to determine the exact capacity of
the mould by using cocoa butter.
Procedure:
Make sure that the two halves of the suppository mould given are having
the same number.
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Lubricate the mould with soap lubricant by means of a cotton piece;
invert the mould on a porcelain slab to allow the excess of lubricating
solution to drain.
Weigh an amount of CB (5 g if you are supplied with a mould of one
gram and 10 g if you are supplied with a mould of 2 g capacity) to
prepare 3 suppositories (there is a slight excess for mechanical loss)
and melt it in a porcelain dish by exposing the crucible for few
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.
Pour gradually into a continuous stream the melted CB into the
lubricated mould and allow the melted mass to over-fill to avoid the
formation of holes after cooling (due to contraction of the mass).
Cool the filled mass for about 10 minutes, and after cooling remove the
excess CB by a sharp knife.
Weigh accurately certain number of suppositories and then calculate the
average weight.
Calculate the correction factor (F):
Average weight of one suppository
Correction factor = -------------------------------------------------------------
Nominal capacity of the mould (written on the
mould).
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Example: calculate the correction factor for a mould of 2 g capacity in which 5
suppositories weighing 10.5 g were prepared.
CALCULATION OF THE DISPLACEMENT VALUE OF SOLID
MEDICAMENT IN SUPPOSITORIES (USING COCOA BUTTER)
 Displacement value: ‘is the amount of medicament which displaces one
part of cocoa butter’.
 If the medicament you are going to incorporate in CB base has a density of
approximately that of CB, 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 CB.
Practical:
Determine the displacement value of 10% ZnO in cocoa butter base.
Calculations:
To prepare 3 plain and medicated suppositories:
1. Plain suppositories:
 No. of supp. =
 Amount of CB (total weight)
=no. of supp. X mould
capacity
=
2. Medicated suppositories:
 No. of supp. =
 Amount of drug = (10/100) x (total wt.)
=
Or
g ZnO ----- (in mould 1g)
=
g ZnO ----- (in mould 2 g)



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 Amount of base = [(no. of supp. X mould capacity) – drug]
=
g CB ----------- (in mould 1 g)
Or =
g CB ---------- (in mould 2 g)
Procedure:
1. preparation of plain CB suppositories:
Lubricate the mould with soap lubricant, invert on a glass slab to drain
the excess lubricant.
Weigh the required amount of CB, and cut into small pieces by a knife
(or use shredded CB). Place in a porcelain dish and expose it
carefully to the steam of a water bath until a creamy mass which can
be easily poured is produced (use a glass rod instead of the pestle to
aid melting and mixing and to avoid loss in weight).
Pour (in a continuous stream) the melted mass into the lubricated mould
and allow over-filling of the cavities (to avoid formation of holes that
could take place due to contraction of the base on cooling).
Cool in an ice bath (or in the refrigerator) for 10 min.
Remove the excess of the base by means of a knife, take out the supp.
From the mould.
Weigh the suppositories and calculate the average weight (= a).
2. Preparation of the medicated CB suppositories:
a. Use the same mould utilized in the preparation of the plain CB
suppositories and prepare it as mentioned before (Lubricate the mould
with soap lubricant, invert on a glass slab to drain the excess
lubricant).
b. Weigh the required amount of CB, and cut into small pieces by a
knife (or use shredded CB). Place in a porcelain dish and expose it
carefully to the steam of a water bath until a creamy mass which can
be easily poured is produced (use a glass rod instead of the pestle to
aid melting and mixing and to avoid loss in weight).
20
c. Add the calculated amount of pulverized and sifted medicament
(ZnO) to the melted CB, and mix until a uniform and homogenous
mixture is produced.
d. Pour (in a continuous stream) the homogenous mixture (step # c) into
the lubricated mould and allow over-filling of the cavities (to avoid
formation of holes that could take place due to contraction of the base
on cooling).
e. Cool in an ice bath (or in the refrigerator) for 10 min.
f. Remove the excess of the base by means of a knife, take out the supp.
From the mould.
g. Weigh the suppositories and calculate the average weight (= b).
Procedure for Calculation of the displacement value of 10% ZnO in CB
base:
The average wt of the plain supp. = a.
The average wt of the medicated supp containing 10% of the drug =
b.
calculate the amount of theobroma oil (CB) in the medicated supp:
CB = b x (90/100) = c
Medicament = b x (10/100) = d
calculate the amount of CB displaced by the medicament = a – c
calculate the displacement value (DV) of the medicament:
wt. Of medicament
d
D.V. = ---------------------------------------------------- = -----------Wt. Of CB displaced by the medicament
Results:
21
a–c
OLEAGINOUS SUPPOSITORY BASES
COCOA BUTTER BASE
Cocoa butter is a natural fat, yellowish-white solid with an odor of chocolate. It
is composed of a mixture of glyceryl esters of stearic acid, palmitic acid, oleic
acid, and other fatty acids.
Advantages of CB as a suppository base:
It has a melting point of range of 30 – 36 oC (i.e., solid at room temp.
but melts at the body temp.).
Non toxic and non irritant.
Miscible with many ingredients.
Readily melts on warming and rapid setting on cooling.
Disadvantages of CB:
Polymorphism: when CB is melted and cooled, it solidifies in
different crystalline forms, depending on the temperature of
melting and rate of cooling. If it is melted at not more than 36 oC
and slowly cooled, it forms stable beta crystals with normal
melting point. However, if it is over-heated and suddenly cooled,
it may produce the  form and the  form is obtained by sudden
cooling of the melted CB to 0 oC.
Adherence to the sides of the mould, so it needs lubrication of the
mould.
Rancidity on storage due to oxidation of unsaturated glycerides.
Leakage from the body cavities (rectum and vagina),so CB is rarely
used as a pessary base.
It contracts forming a hole at the top of the suppository, so pouring
is made by excess.
Expensive.
Poor water absorbing ability and this can be improved by the
addition of emulsifying agents.
22
When the melting point is reduced by soluble ingredient (e.g.,
chloral hydrate), additives such as bees wax or spermaceti may be
incorporated to counteract the effects of medicaments and/or
climates.
Practical:
Prepare 3 aminophyllin suppositories each having the following formula:
Rx
Aminophyllin
gr V
Cocoa butter
Q.S.
Fiat: supp.
Mitte: III
Sig.: MDU.
DV of aminophyllin = 1.59
Calculations:
1. No. of supp. =
2. amount of drug =
3. amount of base = [No. of supp. X mould capacity – (drug / DV)]
x CF
=
g --------- for mould 2 g
=
g --------- for mould 1 g
Procedure:
1. Prepare the mould (clean, dry, lubricate with soap lubricant then
invert on a glass slab to drain the excess lubricant).
2. Weigh the required amount of CB, and cut into small pieces by a
knife (or use shredded CB). Place in a porcelain dish and expose
it carefully to the steam of a water bath until a creamy mass,
which can be easily poured, is produced. (Avoid overheating, to
avoid polymorphism).
23
3. Powder the drug (if necessary) in a mortar with a pestle, then
weigh the required amount.
4. Add the calculated amount of pulverized and sifted medicament
(aminophyllin) to the melted CB, and mix well with a pestle until
a uniform and homogenous mixture is produced.
5. Pour (in a continuous stream) the homogenous mixture (step # 3)
into the lubricated mould and allow over-filling of the cavities (to
avoid formation of holes that could take place due to contraction
of the base on cooling).
6. Cool in an ice bath (or in the refrigerator) for 10 min.
7. Remove the excess of the base by means of a knife, take out the
supp. From the mould.
8. Wrap the suppositories in aluminum foil paper, and then fix a red
label.
Label:
Use:
Treatment of bronchial asthma.
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SOLUBLE SUPPOSITORY BASES
1. MACROGOLS (POLYETHYLENE GLYCOLS):
 These are polymers of ethylene oxide, H(CH2-O-CH2)n OH, with
different molecular weights ranging from 200 to 20000.
 At room temperature, the lower members of the series are liquids, while
the PEG 1000 and PEG 1450 are soft solids and the higher members are
wax-like.
 Advantages:
1. No laxative effect is produced.
2. Not susceptible to microbial contamination.
3. No lubricant is to be used with these bases because they do not
adhere to the mould.
4. Melting points (37-63 oC ) are above body temperature, so cool
storage is not so critical, and therefore, they are suitable for areas
with hot climate. Moreover, they do not melt on handling. This high
melting point means that the base doesn’t melt but dissolve in rectal
fluids at body temperature, and disperse the medicament.
5. They produce high viscosity solutions. This means that after
dispersion in the body fluid, leakage is less likely to occur.
6. They give products with clean smooth appearance.
7. They do not alter by overheating.
 Disadvantages:
1. Hygroscopic: so they may cause irritation to the rectal mucosa. This
can be overcome by incorporation of 20% of water in the mass, or by
instructing the patient to dip the preparation in water before
insertion.
25
2. Incompatibilities: macrogol bases are incompatible with some drugs
(e.g., bismuth salts, ichthammol, benzocaine, and phenol). Also, they
interact with some plastics which limits the choice of containers.
3. Brittleness: macrogol bases may be brittle unless poured at as low a
temperature as possible.
 The following mixtures of polyethylene glycols of varying hardness have
been described for the use as suppository bases:
Mixture
Macrogol
1
2
3
4
5
PEG 6000
47%
47%
47%
---
---
PEG 4000
33%
33%
---
25%
4%
PEG 1540
---
---
33%
---
---
PEG 1000
---
---
---
75%
96%
PEG 400
20%
---
---
---
---
Water
---
20%
20%
---
---
Practical:
Prepare 3 paracetamol suppositories each having the following formula:
Rx
Paracetamol
Carbowax
200 mg
QS to
2g
Carbowax base:
*F
PEG 6000
47%
PEG 4000
33%
PEG 400
20%
Fiat: supp.
Mitte:III
Sig.: one supp. P.r.n.
26
N.B.: CF of the base =1
DV of paracetamol = 1.5
Calculations:
1. No. of supp. =
2. amount of drug =
3. amount of base = [No. of supp. X mould capacity – (drug / DV)] x
CF
=
g -------- for mould 2 g
4. F =
Procedure:
1. Prepare the mould (clean and dry, no need for lubrication).
2. Weigh the required amounts of PEGs. Place in a porcelain dish and
expose to the steam of a water bath (starting with the higher
mol.wt. polymer , high melting point) until complete melting is
achieved.
3. Powder the drug (if necessary) in a mortar with a pestle, then
weigh the required amount.
4. Add the calculated amount of pulverized and sifted medicament
(paracetamol) to the melted base, and mix well with a pestle until a
uniform and homogenous mixture is produced.
5. Pour (in a continuous stream) the homogenous mixture (step # 4)
into the dry mould and allow over-filling of the cavities (to avoid
formation of holes that could take place due to contraction of the
base on cooling).
6. Cool in an ice bath (or in the refrigerator) for 10 min.
7. Remove the excess of the base by means of a knife, smooth the
surface then take the supp. out the mould.
8. Wrap the suppositories in aluminum foil paper, and then fix a red
label.
27
Label:
Use:
Analgesic and antipyretic.
2. GLYCEROGELATIN BASE:
 This base is a mixture of glycerin and water gelled by the addition of
gelatin.
 Glycerol suppository mass usually contains 70% glycerol and a
minimum of 14% gelatin. Higher concentrations of gelatin may be
required for use in hot countries or to counteract the softening effect of
any liquid ingredients included in the product.
 Gelatin is derived from the hydrolysis of animal collagenous tissues
including skin and bones.
Type A gelatin is prepared by acid hydrolysis at p H: 3.2, while
Type B gelatin is prepared by a alkaline hydrolysis at pH: 7-8.
 Disadvantages:
1. It has a laxative effect.
2. Unpredictable solution time: this varies with the batch of gelatin and
the age of the base.
3. Hygroscopic: the base needs protection from heat and moisture.
Also, it has a dehydrating effect on the rectal or vaginal mucosa
leading to irritation.
28
4. Microbial contamination is likely: this base may require the addition
of preservatives, which may lead to problems of incompatibilities.
5. Long preparation time, compared to fatty bases.
6. Difficult to remove from the mould: so lubrication of the mould is
essential.
 The specific gravity of glycerogelatin base is much higher than that of
cocoa butter and this depends upon the proportion of the glycerin used
in the formula. Thus the capacity of the mould must be corrected when
glycerogelatin base is to be prepared.
 The mould should be lubricated with liquid paraffin or any other oil
by means of a cotton piece, then invert the mould on a glass slab to
drain the excess of the lubricant.
 The mass doesn’t contract on cooling. So, take care just to fill the
cavities of the mould on pouring.
 Different formulae for the glycerogelatin base include:
1. The B.P. formula: (glycerin suppositories)
Rx
Gelatin
14 g
Glycerin
70 g
Water
QS
 This base is suitable for medicated suppositories and pessaries containing
solid medicaments or not more than 20% of semi-solid or liquid
medicaments. With more than this, the mass becomes too soft.
2. The U.S.P. formula: (glycerinated gelatin suppositories)
Rx
Gelatin
20 g
Glycerin
70 g
Water to 100 g
29
Practical :
Prepare 3 suppositories of zinc oxide in glycerogelatin base having the
following formula:
Rx
zinc oxide
0.2 g
Glycerogelatin base
q.s.
Glycerogelatin base:
*F
Gelatin
14 g
Glycerol
70 g
Water to
100 g
Fiat: supp.
Mitte: III
Sig. MDU.
N.B.: D.V. of zinc oxide = 4
CF of the base = 1.2
Calculations:
1. No. of supp. =
2. amount of water =
3. amount of drug =
4. amount of base = [(No. of supp. X mould capacity) – Drug/DV ]
x CF
=
-------- for mould 2 g
=
--------- for mould 1 g
5. F =
Procedure:
1. Prepare the mould (clean, then lubricate with liquid paraffin and invert
on a glass slab to drain the excess lubricant).
30
2. in a porcelain dish, soak gelatin powder in the calculated amount of
water, for about 5-10 minutes until it is completely wetted (hydrated)
and swelled. Then transfer the dish over water bath.
3. Add glycerin to the soaked gelatin. Leave on water bath, stir gently (in
cross lines) to avoid air entrapment, until complete solubility of
gelatin and the formation of a translucent mass (free of air bubbles).
4. Powder zinc oxide finely, and then add to the base. Stir gently with a
glass rod (to avoid air entrapment) until a smooth mass results and a
drop of the solution becomes a line or a thread.
5. Pour the mass into the lubricated mould, and just fill the cavities of the
mould (no overfilling).
6. Cool in an ice bath (or in the refrigerator) for 10 min.
7. Remove the supp. out the mould.
8. Wrap the suppositories in aluminum foil paper, and then fix a red
label.
Label:
Red
Use:
Astringent.
31
3. SOAP GLYCERIN SUPPOSITORIES:
 Stearin soap (curd soap) has certain advantages over gelatin for making
glycerin sufficiently hard for suppositories.
 A larger quantity of glycerin can be incorporated actually up to 95% of
the mass.
 Soap assists the action of glycerin, whereas gelatin does not.
 This base is very hygroscopic and requires to be wrapped immediately (in
foil paper) and protected from light.
Practical:
Prepare 3 soap glycerin suppositories having the following formula:
Rx
*F
Glycerol
90 g
Sodium carbonate
2.5 g
Stearic acid
7.5 g
Fiat: supp.
Mitte: III
Sig. MDU.
Calculations:
1. No. of supp. =
2. amount of base (total weight) = [No. of supp. X mould capacity ]
x CF
=
g --------- for mould 2 g
=
g --------- for mould 1 g
3. F =
Procedure:
1. Prepare the mould (clean, then lubricate with liquid paraffin and invert
on a glass slab to drain the excess lubricant).
32
2. Heat glycerin in a small beaker over a sand bath until it reaches 70 oC.
(Check with a thermometer).
3. When glycerin reaches the assigned temperature, add sodium carbonate,
stir with a glass rod until complete dissolving of the solid.
4. Add stearic acid powder and stir until all effervescence ceases and the
solution is complete (clear solution).
5. Skim the surface with a spatula or a glass rod to remove the remaining
froth.
6. Pour the solution into the lubricated mould, and allow for overfilling.
7. Cool in an ice bath (or in the refrigerator) for 10 min.
8. Remove the excess, smooth the surface and take the supp. out the
mould.
9. Wrap the suppositories in aluminum foil paper, and then fix a red
label.
Label:
Use:
Laxative (in the treatment of constipation).
33
Another formula for soap glycerin suppositories:
Prepare 3 soap glycerin suppositories having the following formula:
Rx
*F
Glycerol
91 g
Sodium stearate
9g
Water
5g
Fiat: supp.
Mitte: III
Sig. MDU.
Calculations:
1. No. of supp. =
2. amount of base (total weight) = [No. of supp. X mould capacity ]
x CF
=
g --------- for mould 2 g
=
g --------- for mould 1
g
3. F =
Procedure:
Prepare the mould (clean, then lubricate with liquid paraffin and invert on a
glass slab to drain the excess lubricant).
Heat glycerin in a small beaker over a sand bath until it reaches 70 oC.
(Check with a thermometer).
When glycerin reaches the assigned temperature, add sodium stearate, stir
with a glass rod until complete dissolving of the solid.
Add water.
Pour the solution into the lubricated mould, and allow for overfilling.
Cool in an ice bath (or in the refrigerator) for 10 min.
Remove the excess, smooth the surface and take the supp. out the
mould.
Wrap the suppositories in aluminum foil paper, and then fix a red
label.
34
Label:
Use:
Laxative (in the treatment of constipation).
COMPRESSED TABLETS
Compressed tablets are solid dosage forms prepared by compaction of a
formulation containing the drug and certain excipients selected to aid the
processing and improve the properties of the product.
Tablets excipients:
1. Bulking agents (diluents):
These are used to increase the bulk of the tablet.
Examples:
a. Soluble: lactose, sucrose, mannitol, sorbitol.
b. Insoluble: calcium sulphate, dicalcium phosphate,
tricalcium phosphate, calcium carbonate, starch.
2. Binders (adhesives):
 The substances that glue the powders together and cause them to form
granules are binders or adhesives.
35
 Binders are added either dry or in a liquid form during wet granulation to
form granules or to promote cohesive compacts for directly compressed
tablets.
 A list of binders used in wet granulation is shown in the following table:
Table : some commonly used binders and granulating liquids:
Binder
comments
Strength
Water
----------- ---------------------------------------
Ethanol
----------- ---------------------------------------
Acacia mucilage 10-20%
Tragacanth
Hard, friable granules
10-20%
Same as acacia
Gelatin solution
2-10%
Strong adhesive, use warm.
Starch mucilage
2%
One of the best general adhesives, use warm.
Glucose syrup
25-50%
Sucrose syrup
65-83%
Same as glucose.
PVP
3-15%
----------------------------------------------
5-10%
-----------------------------------------------
nucilage
Cellulose
derivatives
Strong adhesive, tablets may soften in high
humidity.
3. Lubricants, glidants, and anti-adherents:
a. Lubricants:
Are those agents that reduce the friction between the tablet edges and
die wall during the ejection cycle, e.g., magnesium stearate.
b. Glidants:
Are materials that improve the flow characteristics of granulation by
reducing friction between the particles, e.g., talc.
c. Anti-adherents:
36
These function to prevent tablet granulation from sticking or adhesion to
the faces of the punches and the die walls, e.g., talc.
 Lubricants, glidants and antiadherents are added at the very last step
before compression, since they must be present on the surface of the
granules and in between them and in the parts of the tablet press.
4. Disintegrants:
Disintegrant is a term applied to substances added to a tablet granulation
for the purpose of causing the compressed tablets to break apart when placed
into an aqueous environment.
Methods of adding disintegrant:
Disintegrants could be added in the first step before granulation, or in
the last step just before compression. However, it is better to add it in two
portions, one half is added to the powdered components before the wet
granulation process and the other remaining portion is added to the finished
granulation just prior to compression. This method holds that a disintegrant is
required between the granules as well as within them.
Some of the commonly used disintegrants are listed in the table:
Table: disintegrants: typical amounts used:
Disintegrant
Concentration (% w/w)
Starch
5-20%
Avicel
5-20%
Algenic acid
5-10%
Veegum
5-15%
Bentonite
5-15%
METHODS OF MANUFACTURE
37
1. Direct compression method:
 Direct compression method involves compressing the tablet from
powdered material without modifying the physical nature of the material
itself.
 Drugs characterized by high dose, poor compressibility and poor fluidity
(flow) do not lend themselves to direct compression method. On the other
hand, small doses can be mixed with direct compressible vehicle before
compression into a tablet.
 Direct compressible vehicle is an inert substance that may be compressed
directly without difficulty and which may be compressed even when small
quantities of drug are mixed with it.
 Direct compression vehicles should have:
 High fluidity,
 High compressibility, and
 Should be inert and compatible with all of the active ingredients.
 Advantages:
1. Economy (less areas, reduced processing time, reduced labor costs, and
fewer manufacturing steps).
2. Elimination of heat and moisture.
3. Stability.
2. Dry granulation (slugging) method:
 This method involves the compaction of the components of tablet
formulations by means of tablet press or specially designed machinery
followed by milling and screening prior to final compression into a tablet,
i.e., the granulation of powder mixture is carried out by compression and
without the use of heat and solvent.
 On a relative basis, it is the least desirable of all of the methods of
preparing tablet granulation. However, when direct compression is not
possible due to the properties and dose of the drug, and wet granulation
38
can not be used because the drug is sensitive to moisture and heat, then
dry granulation remains the only method available.
 Advantages:
1. Suitable for moisture and heat sensitive materials.
2. Results in an improved disintegration, since powder particles are not
bonded together by a binder.
 Disadvantages:
Requires a specialized heavy duty tablet press to form slugs.
Creates more dust than wet granulation.
Does not permit uniform color distribution.
3. Wet granulation:
The preparation of granulation for tabletting by wet granulation is the oldest
method and still the most widely used.
Steps of wet granulation:
1. Milling of drug and excipients.
2. Mixing of the milled powders.
3. Preparation of binder solution.
4. Mixing of binder solution with powder mixture to form wet mass.
5. Course screening of wet mass using 6-12 mesh screen.
6. Drying of moist granules.
7. Screening of dry granules through 20/35 mesh screen.
8. Mixing of screened granules with lubricant and the remaining
disintegrant.
9. Tablet compression.
Advantages:
Improved cohesiveness & compressibility of powders due to added binders.
Suitable for high-dosage drugs having poor flow or compressibility
properties.
Good distribution for low dosage drugs and color additives.
Disadvantages:
39
1. High cost (because of the time, equipments and space requirements).
2. Not suitable for moisture and heat sensitive drugs.
PREPARATION OF ACETAMINOPHEN TABLETS (150 mg) BY WET
GRANULATION METHID
Prepare 500 acetaminophen tablets each containing 150 mg of the drug and the
total tablet weight is 225 mg:
Rx
*F
Acetaminophen
150 mg
(66.67%)
(binder)Polyvinylpyrrolidone
11.25 mg
(5%)
(diluent)Lactose
28.625 mg
(12.72%)
Alcohol
Q.S.
Starch
21.625 mg
(9.61%)
6.75 mg
(3%)
(glidant)
Talc
(lubricant)Magnesium stearate
4.5 mg
(2%)
Calculations:
1. add 20 % excess to compensate for the mechanical loss:
No. of tablets =
2. F=
Method of preparation (wet granulation):
1. Mix acetaminophen with PVP, lactose, and half the amount of starch.
(Mixing is to be made geometrically in a large dish or in a jar by
tumbling for 15 minutes).
2. Add alcohol slowly to form a wet mass which retain its shape on
handling.
3. Screen the wet mass through a mesh-12 sieve to get the granules.
40
4. Dry the granules at 50 oC overnight (in an oven).
5. Make size reduction for the dried granules through a mesh-20 sieve (0.8
mm).
6. Weigh the granules (W), then add the remaining half of starch, talc and
Mg stearate:
Remaining starch
= (4.81/100) x W
Talc
= (3/100) x W
Mg stearate
= (2/100) x W
7. Mix the ingredients in a jar by tumbling for 15 min.
8. Compress.
Lab # 3
TABLET EVALUATION
41
Compressed tablets may be characterized or described by a number of
specifications. These include: shape, diameter, thickness, weight, hardness,
friability, disintegration time and dissolution characteristics.
Diameter and shape:
 The diameter and shape depend on the die and punches selected for the
compression of the tablet.
 Generally, tablets are discoid in shape, although they may be oval, oblong,
round, cylindrical, or triangular. Their upper and lower surfaces may be
flat, round, concave or convex to various degrees. The tablets may be
scored in halves or quadrants to facilitate breaking if smaller dose is
desired. The top or lower surface may be embossed or engraved with a
symbol or letters which serve as an additional mean of identifying the
source of the tablets. These characteristics along with the color of the
tablets tend to make them distinctive and identifiable with the active
ingredient which they contain.
Tablet thickness:
The thickness of the tablet is the only dimensional variable related to the
compression process.
The thickness of individual tablets may be measured with a micrometer.
 Thickness should be controlled within ± 5% variation of a standard value.
 Thickness must be controlled for consumer acceptance of the product, and
to facilitate packaging.
QUALITY CONTROL TESTS OF TABLETS
UNOFFICIAL TESTS
42
1. HARDNESS (CRUSHING STRENGTH):
 Tablets require a certain amount of strength, or hardness to withstand
mechanical shocks of handling in manufacture, packaging and shipping.
 Recently, the relationship of hardness to tablet disintegration and the drug
dissolution (release) rate has become apparent.
 Tablet hardness can be defined as the force required to break a tablet in a
diametric compression test.
 Several devices operating in this manner have been used to test tablet
hardness, e.g., the Erweka hardness tester.
 Hardness determinations are made throughout the tablet runs to
determine the need for pressure adjustments on the tabletting machine. If
the tablet is too hard, it may not disintegrate in the require period of time to
meet the dissolution specifications, and if it is too soft, it will not withstand
the handling, packaging and shipping operations.
Method:
Carry out the test on the batch of tablets provided using Erweka hardness tester.
Calculate the mean crushing strength of 10 tablets (taken randomly).
N.B., a crushing strength of 4-8 Kg for uncoated tablets is acceptable.
2. FRIABILITY TEST:
Tablets that tend to powder, chip, and fragment when handled lack elegance
and consumer acceptance, and can create excessively dirty processes
in such areas of manufacturing as coating and packaging. They can also
add to tablet’s weight variation or content uniformity problems.
The measurement of friability is made by Roche friabilator.
43
Method:
1. Select 20 tablets randomly, and weigh (WO).
2. Place the tablets in the Roche friabilator drum; switch on the apparatus
adjusting the timer at 4 min. and the speed at 25 rpm.
3. At the end of this operation, remove the tablets from the friabilator,
dedust and reweigh (W). (Any tablet that breaks up should be rejected
before reweighing).
4. friability is expressed as a percentage loss in weight: i.e.,
% loss =
WO  W
x 100
WO
N.B., if the value of friability (% loss) is less than or equal to 1%, the batch
is accepted.
RESULTS
1. Thickness:
Tab. No.
Average
Thickness
thickness
(cm)
(cm)
Upper
limit
1.
2.
3.
4.
5.
2. Diameter:
44
Lower
limit
Comment
Tab. No.
Diameter
(cm)
Average
diameter
(cm)
Hardness
(Kg)
Average
hardness
(Kg)
Upper
limit
Lower
limit
1.
2.
3.
4.
5.
3. Hardness:
Tab. No
Comment
4. Friability:
Weight of 20 tablets =
Weight of the tablets ( after 4 min in the friabilator) =
% loss in weight =
comment:
Lab # 4
EVALUATION OF TABLETS (CONT.)
OFFICIAL TESTS
45
Comment
1. DISINTEGRATION TEST:
 Disintegration test is a measure of the time required for a group of
tablets to break up into particles under a given set of conditions.
The USP disintegration apparatus:
 This apparatus consists of a basket rack containing 6-open-ended glass
tubes held in a vertical position. A number 10-mesh stainless steel wire
screen is attached to the bottom.
 To be in compliance with the USP standards, the tablets must
disintegrate, and all of the particles must pass through the 10-mesh
screen in the time specified. If any residue remains, it must have a soft
mass with no palpably firm core.
 Limit:
 Uncoated USP tablets have disintegration time standards as low as 5
minutes (aspirin tablets), but the majority of tablets have maximum
disintegration time of 30 minutes.
 N.B., if one tablet fails to disintegrate within 30 minutes, the
disintegration test is repeated on 12 additional tablets. Not less than 16
out oh the total 18 tablets tested disintegrate completely within 30
minutes.
Method:
1. Place one tablet in each of the six tubes of the basket (tablets are
selected randomly).
2. Position the basket rack in 1- L beaker containing distilled water (as the
disintegration medium) maintained at 37 oC.
3. Start the apparatus (to move the basket assembly containing the tablets),
and record the time required for all of the six tablets to break into
particles and to pass to the disintegration medium.
46
2. WEIGHT VARIATION (UNIFORMITY OF WEIGHT) TEST:
 The weight of the tablets being made should be routinely measured to
help ensure that the tablet contains the proper amount of drug.
 The USP weight variation test is run by weighing 20 tablets individually,
calculating the average weight, and comparing the individual tablet
weights to the average.
 The weight variation tolerances for uncoated tablets differ depending on
average tablet weight. (See the next table)
Table : Weight variation tolerances for uncoated tablets:
Average weight
Maximum %
of tablets (mg)
difference
allowed
Less than 130
± 10
130 – 324
± 7.5
More than 324
± 5
Method:
1. Select 20 tablets randomly from the batch provided, and then weigh the
tablets individually.
2. Weigh the 20 tablets together and calculate the average weight (W).
3. Compare the average weight calculated to the previous table to
determine the maximum % difference allowed.
4. calculate the upper and lower limits at the % difference allowed:
Upper limit = W + [(%/100) (W)]
Lower limit = W – [(%/100) (W)]
5. Furthermore, calculate the upper and lower limits at double the %
difference allowed:
Upper limit = W + [(2x %/100) (W)]
Lower limit = W – [(2x % /100) (W)]
47
6. Compare the individual weights of tablets to the upper and lower limits
calculated at the % difference allowed and at double that percentage.
7. Comment on the results.
Limit:
For the batch to be accepted:
2. Not more than 2 tablets (out of the 20 tablets) differ from the average
weight by the % difference listed, and
3. No tablet differs from the average weight by double that percentage.
RESULTS
1. Disintegration test:
 Time recorded for the tablets to break into particles and pass to the
liquid medium = ----------------- minutes.
 Comment:
2. Weight variation test:
 Total weight of tablets
=
 Average weight of tablets (W)
= total wt. / 20 =
 Upper limit (at the % diff. Allowed)
= W + [(%/100) (W)]
=
 Lower limit (at the % diff. Allowed)
= W - [(%/100) (W)]
=
 Upper limit (at double the % diff. Allowed) = W + [(double%/100)
(W)]
=
 Lower limit (at double the % diff. Allowed) = W - [(double%/100)
(W)]
=
48
Tab.
No.
Weight (g)
Comparison at %
difference
allowed
Comparison at double %
difference allowed
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Comment:
Lab # 5
3. DRUG CONTENT:
Range:
Official compendia or other standards provide an acceptable potency range
around the label potency.
49
 For highly potent, low-dose drugs such as digitoxin, this range is usually
not less than 90% and not more than 110% of the labeled amount.
 For most other larger – dose drugs in tablet form, the official potency
range that is permitted is not less than 95% and not more than 105% of
the labeled amount.
 For less potent, low-dose drugs such as indomethacin, the official
potency range that is permitted is not less than 85% and not more than
115% of the labeled amount.
Three factors that can directly contribute to content uniformity problems
in tablets:
1. Non-uniform distribution of the drug throughout the powder mixture or
granulation.
2. Segregation (demixing) of powder mixture or granulation during the
various manufacturing processes.
3. Tablet weight variation.
DETERMINATION OF DRUG CONTENT OF ASPIRIN TABLETS
(B.P.)
1. Weigh and powder 20 tablets. (Powder in a dry mortar).
2. Weigh an amount of the powder equivalent to 0.5 g of aspirin.
3. Place the calculated amount in a conical flask, and add 30 ml of 0.5 M
NaOH solution (by burette). Boil gently on a hot plate, for 10 minutes;
(cover the flask).
4. Cool, and then make back titration of the excess NaOH with 0.5 M HCl,
using phenol red indicator. (E.P.: red to yellow color).
5. Repeat the above operation without the drug. (Blank).
6. Calculate the content of aspirin.
N.B., each ml of 0.5 M NaOH is equivalent to 0.04504 g of aspirin. (F).
Content: tablets should contain 95 – 105 % of the prescribed or stated
amount.
Results for drug content of aspirin tablets:
50
% aspirin
=
( B  Exp) xFxfx100
0.5
=
Comment:
Lab # 6
4. DISSOLUTION TEST
51
The dissolution test: is an in vitro test for measuring the time required for a
given percentage of the drug substance in a tablet to go into solution under a
specified set of conditions.
USP / NF have provided procedures for dissolution testing:
Apparatus I (USP basket method): in general, a single tablet is placed in
a small wire mesh basket fastened to the bottom of the shaft connected
to a variable speed motor. The basket is immersed in the dissolution
medium contained in 1000 ml flask. The flask is maintained at 37 ± 0.5
o
C by a constant temperature water bath. Samples of the fluid are
withdrawn at specified time intervals to determine the amount of the
drug in solution.
Apparatus II (USP paddle method): the same equipment as in apparatus I
is used, except that the basket is replaced by a paddle, formed from a
blade and a shaft, as the stirring element. The dosage form is allowed to
sink to the bottom of the flask before stirring.
Description of a dissolution test in USP/NF monograph specifies:
The dissolution test medium, and volume,
Which apparatus is to be used,
The speed at which the test is to be performed (rpm),
The time limit for the test, and
The assay procedure.
The test tolerance is expressed as:
The percentage of the labeled amount of the drug dissolved in the time
limit.
The results are plotted as concentration vs. time. Values for t 50% , t 90%, and
the percentage dissolved in 30 minutes are used as guides. The value for
t 50% is the length of time required for 50% of the drug to go into
solution.
DISSOLUTION TEST FOR ASPIRIN TABLETS
(U.S.P. 1995)
52
Conditions:
o apparatus :
I (basket)
o medium :
500 ml of 0.05 M acetate buffer pH 4.5
o Temp.
o speed
: 37 ± 0.5 oC
:
o Time
50 rpm
: 30 min.
Procedure:
1. Place one tablet in the basket, immerse in the vessel, and then start the
apparatus at the above conditions.
2. At specified time intervals (5, 10, 15, 20, 25, 30, and 45 min) withdraw
5 ml sample from the dissolution medium, through a Millipore filtration
unit (polyethylene tube with a cotton), and place the sample in a test
tube.
3. Replace the withdrawn sample with 5 ml fresh acetate buffer kept at 37
± 0.5o C.
4. Dilute 1 ml of the collected sample to 5, 10, 20 or 25 ml (dilution factor
= 1:5, 11:10, 1:20 or 1:25) with fresh acetate buffer (in a volumetric
flask), mix well. (Dilution is made if necessary.)
5. Read the absorbance for the diluted samples at 265 nm against a blank
of acetate buffer.
6. Calculate the concentration of aspirin released (taking 0.036 as the value
of E1mg%), and express this conc. As a percentage of the labeled amount.
7. Plot the dissolution curve of aspirin (% released vs. time).
8. From the dissolution curve, determine the time required for 80% of the
labeled amount of the drug to be released (go into solution), i.e., t 80%.
Tolerance: the tablet should release not less than 80% of its content within 30
minutes.
Results of the dissolution of aspirin tablets: (Bayer tablets, 300 mg)
53
Time
(min)
Abs.
at
265
nm
Dilution
factor =
( total vol /
vol taken
from the
sample)
Conc. =
abs.
x dil
E1mg %
factor x 5
(mg/500ml)
5
10
15
20
25
30
45
Plot of the Dissolution curve (on a graph paper):
Comment:
54
% released
=
conc.
x 100
strength
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