IPQC TESTS FOR

OINTMENTS
&
CREAMS
PRESENTATION BY-
JADHAV SAURABH
M.PHARM F.Y.(QAT)

1/21/2020
AISSMS COLLEGE OF PHARMACY 1
 PRESENTATION OUTLINE
IDEAL PROPERTIES
CREAMS
Test According To-
1.INDIAN PHARMACOPOEIA
2.BRITISH PHARMACOPOEIA
OINTMENTS
Test According To-
1.INDIAN PHARMACOPOEIA
2.BRITISH PHARMACOPOEIA
3.UNITED STATES PHARMACOPOEIA
GENERAL TESTS
REFERENCES
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IDEAL PROPERTIES

1. PHYSICAL PROPERTIES
a) Smooth texture
b) Elegant in appearance
c) Non dehydrating
d) Non gritty
e) Non greasy and non staining
f) Non hygroscopic
2. PHYSIOLOGICAL PROPERTIES:
a) Non irritating
b) Do not alter membrane / skin functioning
c) Miscible with skin secretion
d) Have low sensitization effect
3. APPLICATION PROPERTIES:
a) Easily applicable with efficient drug release.
b) Easily washable with water.
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 CREAMS

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 Acc.. To INDIAN PHARMACOPOEIA
Uniformity of weight.

Sterility.

Storage.
Store at temperatures below 25" unless otherwise directed. Do not freeze.

Labelling.
The label states
(1) that the cream is sterile, where necessary;
(2) the name and concentration of any added antimicrobial preservative;
(3) the storage conditions.
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 Acc… to BRITISH PHARMACOPOEIA
 STORAGE-
Creams Should Be Stored At Temperature Not Exceeding 25 C. They Should
Not Be Allowed To Freeze.
 LABELLING –
1) Date After Which Creams Is Not Intended For Use.
2) Conditions Under Which Creams Should Be Stored.
 STERILITY
Method A- Membrane Filtration.
Method B - Direct Inoculation.

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 OINTMENTS

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 Acc.. To INDIAN PHARMACOPOEIA
Non irritant, non sensitive to skin, not retard wound healing.
Smooth, inert, odourless. Physically & chemically stable and compatible with the skin
and with incorporated medicaments.
Consistency
Intended for use on large wounds or on severely injured skin it should be sterile.
Ointments should not normally be diluted; if dilution is necessary care should be taken
to choose the right diluent to avoid risk of instability or incompatibility.

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 STORAGE
 Store at a temperature Not exceeding 30 C otherwise directed. Do not freeze.

LABELLING.
 The label states
(1) that the ointment is sterile, where necessary;
(2) the name and concentration of any added antimicrobial preservative;
(3) the storage conditions

STERILITY
Method A- Membrane Filtration
Method B - Direct Inoculation

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Method A- Membrane Filtration
 Dilute ointments in a fatty base and emulsions of the water-in-oil type to give a fluid
concentration of 1 % w/v, by heating, if necessary, to NMT 40° with a suitable sterile diluent
such as isopropyl myristate previously rendered sterile by filtration through a 0.22/um
membrane filter that has been shown not to have antimicrobial properties under the
conditions of the test.

 Filter as rapidly as possible & Wash the membrane by filtering through it at least three
successive quantities, each of approximately 100 ml, of sterile fluid B or any other
suitable sterile diluent.

 After filtration, aseptically remove the membrane(s) from the holder, transfer the whole
membrane or cut it aseptically into 2 equal parts.

 Transfer one half to each of two suitable media.

 Use the same volume of each medium as in the procedure for :

 Validation of Tests. Alternatively, transfer the medium onto the membrane in the apparatus.
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Method B - Direct Inoculation

 Prepare by diluting to about 1 in 10 ml by emulsifying base with the chosen emulsifying

agent in a suitable sterile diluent such as Fluid A.
 Transfer the diluted product to a medium not contain an emulsifying agent.(Before use test
the E.A. to ascertain that in the conc.. used it has no significant antimicrobial effects during
the time interval for all transfers).
 Mix 10 ml of the fluid mixtures so obtained with the 80 ml of the medium.
 Remove the liquid from the test containers with a sterile pipette or with a sterile syringe or a
needle.
 Transfer the quantity of the preparation under examination prescribed
{ 1. Quantity to be mixed-1to 10 g.
2. Quantity to be used for each culture medium- 0.5 to 1 g Not less than 1 g (1 portion)}
directly into the culture medium so that the volume of the preparation under examination is
not more than 10 per cent of the volume of the medium, unless otherwise prescribed.

 When the quantity in a single container is insufficient to carry out the tests, the combined
contents of two or more containers are to be used to inoculate the media.
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 If the preparation under examination has antimicrobial activity, carry out the test after
neutralizing this with a suitable neutralizing substance or by dilution in a sufficient
quantity of culture medium.

 When it is necessary to use a large volume of the product it may be preferable to use a
concentrated culture medium prepared in such a way that it takes account of the
subsequent dilution. Where appropriate, the concentrated medium may be added directly
to the product in its container.

 Incubate the inoculated media for NLT 14 days. Observe the cultures several times
during the incubation period. Observe the containers of media periodically during the 14
days of incubation.

 If the test specimen is positive before 14 days of incubation, further incubation is not
necessary.

 For products terminally sterilized by a validated moist heat process, incubate the test
specimen
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 Incubate the media for NLT 14 days.
Observe the containers of media periodically during the 14 days of incubation.

 If the test specimen is positive before 14 days of incubation, further incubation is

not necessary.

 For products terminally sterilized by a validated moist heat process, incubate the
test specimen for not less than 7 days.

 In exceptional cases, it may be necessary to heat the substance to not more than 44°
and to use warm solutions for washing the membrane.

 NOTE - For ointments and oils that are insoluble in isopropyl myristate, use
Method B.

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 Acceptance Criteria For Microbiological Quality

Route of TAC (CFU TFC(CFU Specified microorganisms

administration per g per g
or per ml) or per ml)

Transdermal 102 101 1. Staphylococcus aureus - absent in

patches (limits for 1 g or 1 ml
one patch including 2. Pseudomonas aeruginosa -
adhesive layers and absent in 1 g or 1 ml
backing) 3. Bile-tolerant Gram-negative
bacterial-absent 1 g or 1 ml

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 Acceptance Criteria For Microbiological Quality Of raw Materials Of
Natural Origin

Raw materials of Specified microorganisms TAC TFC(CF

natural origin (CFU per U per g
g or per
or per ml) ml)

Used in preparations Staphylococcus aureus - absent in 1 g or 1 ml 103 102

for cutaneous/ topical Pseudomonas aeruginosa - absent in 1 g or 1
use ml

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CONTENT UNIFORMITY
1. Select A sample of 10 filled containers and remove any labelling that might be altered in weight
while removing the contents of the containers.

2. Clean and dry the outer surfaces of the containers and weigh each container.

3. Remove quantitatively the contents from each container.

4. If necessary, cut open the container and wash each empty container with a suitable solvent, taking
care to ensure that

5. Closure and other parts of the container are retained.

6. Dry and again weigh each empty container together with its parts which may have been removed.

7. The difference between the two weights is the net weight of the contents of the container.

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 8.The average net weight of the contents of the 10 containers is NLT the labelled amount.
9. The Net weight of the contents of any SINGLE CONTAINERS is NLT 91 % and
NMT 109 % of the labelled amount ;
where the Labelled Amount is 50 g or less, or NLT 95.5 %
and NMT 104.5 % of the labelled amount where the labelled is more than 50 G but NMT
100g.

1. If this requirement is not met, determine the net weight of the contents of 10 additional
containers. The average net weight of the contents of the 20 containers is NLT the
labelled amount. Net weight of the contents of NMT 1 of the 20 containers is less than
91% or more than 109 % of the labelled amount;
where the labelled amount is 50 g or less than 95 % or more
than 104.5 % of the labelled amount is more than 50 g but not more than 100 g.
2. None of the individual weights deviates by MT twice that of Respective Minimum And
Maximum Percentage Limits.
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 EYE OINTMENTS
Uniformity Of Weight.
Particle Size.
Gently spread a small quantity of the Eye Ointment as a thin layer on a
microscope slide.
Scan under a microscope an area corresponding to 10 ug of the solid
phase.
Scan at least 50 representative fields.
NMT 20 particles have a maximum dimension greater than 25 um,
NMT 10 particles have a maximum dimension greater than 50 um and
none has a maximum dimension greater than 100 um.
Sterility
Comply
1/21/2020
with the test for sterility. 18
 Containers
1. Small, sterilised collapsible tubes of metal or of suitable plastic fitted or provided with
a nozzle of suitable shape to facilitate the application of the product without
contamination and with a cap.
2. The content of such containers is not more that 5 g of the preparation.
3. Eye Ointments may also be packed in single application containers of such a shape as
to facilitate administration without contamination; such containers may be
individually wrapped.

TEST ON CONTAINERS

 Metal Containers
 Select a sample of 50 tubes from the lot to be tested and clean each tube by vibration
and/or "blowing". (A lot may be either the tube manufacturer's day's production or a
consignment delivered to the tube user).
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 Fill the tubes with a suitable molten eye ointment base, close the open end of each tube
by a double fold and allow the filled tubes to cool overnight at a temperature of 15° to
200
 Assemble a metal bacteriological filter with a 4.25-cm filter paper of suitable porosity
supported on suitable perforated plate in place of the standard sintered carbon disc and
heat it in a suitable manner to a temperature above the melting range of the base.
 Remove the caps from the cooled tubes and apply uniform pressure to the closed end of
each tube in, in such a manner that the time taken to express as much of the base as
possible through each nozzle is not less than 20 seconds.
 Collect the extruded base from the 50 tubes in the heated filter, applying suction to the
stem of the filter in order to draw the molten base through the filter paper.
 When the entire melted base has been removed, wash the walls of the filter and the filter
paper with three successive quantities, each of 30 mI, of chloroform, allow the filter
paper to dry and immediately mount it between glasses for examination.
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 Examine the filter paper under oblique lighting with the aid of magnifying glass with a graticule of
1 mm squares, one of which is sub-divided into 0.2 mm squares and note (a) the number of all metal
particles 1 mm in length and longer, (b) the number in the range 0.5 mm to less than 1 rom and (c)
the number in the range 0.2 mm to less than 0.5 mm. Carry out two further examinations with the
filter paper in two different positions so that the lighting comes from different directions and
calculate the average number of metal particles counted in each of the three ranges specified.
 Give each metal particle detected on the filter paper a score as follows and add the scores together.
 Particles 1 mm and above 50
 Particles 0.5 mm but less than 1 rom 10
 Particles 0.2 mm but less than 0.5 rom 2
 Particles less than 0.2 mm

 The lot of tubes passes the test if the total score is less than 100 points; if the total score is more than
150 points, the lot fails the test. If the total score is between 100 and 150· (inclusive), the test is
repeated on a further sample of 50 tubes and the lot passes the test if the sum of total scores in the
two tests is less than 150 points
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 Plastic Containers
Plastics contain - residues from the polymerisation process, plasticisers, stabilisers,
antioxidants, lubricants and pigments.

Factors deciding the suitability of a plastic for use as a container for ophthalmic preparations,
Composition Of The Plastic, Processing And Cleaning Procedures, Contacting Media,
Adhesives, Adsorption And Permeability Of Preservatives, Conditions Of Storage, etc.

Plastic containers for ophthalmic preparations comply with the following tests.

Leakage test. Fill ten containers with water, fit with the intended closures and keep them
inverted at room temperature for 24 hours. There are no signs of leakage from any container.

Collapsibility test. This test is applicable to containers which are to be squeezed to remove the
contents by collapsing inward during use, yields at least 90 % of its nominal contents at the
required rate of flow at ambient temperature.
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Clarity Of Aqueous Extract.
 Select unlabeled, unmarked and non-laminated portions from suitable containers, taken at
Random, sufficient to yield a total area of sample required, taking into account the surface
area of both sides.

 Cut these portions into strips, none of which has a total area of more than 20 cm2
Wash the strips free from extraneous matter by shaking them with at least two separate
portions of distilled water for about 30 seconds in each case, then draining off the water
thoroughly.

 Select cut and washed portions of the sample with a total surface area of 1250cm2, transfer
to a flask, previously cleaned with chromic acid mixture and rinsed with several portions of
distilled water and add 250 ml of distilled water.

 Cover the flask with a beaker and autoclave at 121°for 30 minutes.

 Carry out a blank determination using 250 ml of distilled water.
 Cool and examine the extract; it is COLOURLESS AND FREE FROM TURBIDITY.
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Non-volatile residue.
Evaporate 100 ml of the extract obtained in the test for clarity of aqueous extract to dryness
and dry to
Constant weight at 105°. The residue weighs not more than 12.5 mg.

Systemic injection test; intracutaneous test.

This test is designed to evaluate systemic responses to the extracts of materials under test
following injection into mice.

Eye irritation test.

This test is designed to evaluate responses to the instillation of extracts of material under
examination in the eye of a rabbit.

Extracting media –
(a) sodium chloride injection (b) vegetable oil.

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Test animals.
Select healthy, albino rabbits having no visible eye irritation and not previously used for an eye
irritation test.

The animal house should be designed and maintained so as to exclude sawdust, wood chips, or
other extraneous materials that might produce eye irritation.

Examine both eyes of the animals before testing and use only those animals without eye defects
or eye irritations.

To test the suitability of the rabbit ocular system in use for a given set of samples, select one test
animal and proceed as shown under procedure using 100 ul of a blank prepared as directed
under Systemic injection test in one eye and 100 ul of sterile water for injection in the other eye.

The rabbit ocular system is suitable if no significant differences are found between the two eyes

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Procedure.
 Use three albino rabbits for each extract to be examined. Restrain the animals firmly but
gently until quiet.
 Gently pull the lower lid away from the eyeball to form a cup, and instill about 100 ul of
sterile water for injection.
 Hold the lid together for about 30 seconds.
 Instill into the other eye 100 III of the sample extract prepared as directed under Systemic
injection test.
 Examine the eyes 24, 48 and 72 hours after instillation.
 The requirements of the test are met if the sample extract shows no significant irritant
response during the observation period over that with the blank extract and the rabbit
ocular system is suitable.
 If irritation is observed in the control eye treated with sterile water for injection or if the
rabbit ocular system is shown not to be suitable, repeat the test using three additional
rabbits.
 In the repeat test, all the rabbits meet the test requirement.
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 Acc… to BRITISH PHARMACOPOEIA
Storage-
Ointments should be stored at a temperature not exceeding 25 C unless authorised.
Labelling- label states –
1)date after which ointment is not intended for use.
2) conditions under which ointments should be stored.

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 EYE OINTMENTS
Limit Of Particle Size-
 Gently spread a thin layer of eye ointment on a macroscopic slide. Scan under a microscope
an area corresponding to 10 ug of the solid phase.
 NMT 20 particles have a dimensions greater than 25um, NMT 2 particles have a maximum
dimensions greater than 50um and none has the maximum dimension greater than 90um.
Labelling- Name & concentration of any antimicrobial preservative or other auxiliary
substance added.
Containers- Small collapsible tubes, fitted with the nozzle. Also single dose containers.
Contents –NMT 5g of the preparation.

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STERILITY
A) Membrane Filtration
Normal pore size – 0.45um.
Cellulose nitrate filters.

Method
 For each medium use NLT the quantity of the preparation being examined that is prescribed
in the appropriate section under the application of the tests.

 Ointments in a fatty base and emulsions of w-o type may be diluted to give a final
concentration of 1 % w/v by heating, if necessary, to NMT 40%.

 When it is suspected from the nature of the preparation or process of the preparation that the
organisms of impaired viability may be present, it may be advisable to continue the
incubation period for the longer of 7 days with a suitable sterile diluent, Such as isopropyl
myristate, that does not have antimicrobial properties.
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 Filter as rapidly as possible wash the membrane by filtering three or more successive
quantities, each approximately 100 ml, a suitable sterile diluent such that 0.1 % w/v neutral
solution of meat peptone or casein peptone , that contains either 0.1% w/v of 4-tert-
octylphenoxy) or the 1%w/v of polysorbate 80.

 Either transfer a membrane to each of the culture media used or transfer each medium on to a
membrane.in the apparatus and seal the apparatus so that the medium remains on the
membrane.

 Alternatively transfer the quantity of the preparation being examined for all media to the
membrane, diluting, filtering, and washing as above.

 Aseptically cut the membrane into appropriate no of equal parts and transfer one of each parts
to medium used . Incubate for NLT 7 days.

 At 30 – 35 c in test intended to detect the bacteria and at 20-25c in test intended to detect the
fungi.1/21/2020 30
B) Direct Inoculation Method.

 Prepare by diluting 10 fold in a suitable sterile diluent, such as a 0.1 % w/v

neutral solution of the ,meat or case in Peptone, containing where necessary
the chosen emulsifying agent in an appropriate concentration.

 Transfer the Diluted preparation to the medium containing no E.Agent.

 Incubate the inoculated media for nlt 14 days, at the 30- 35 c to detect
bacteria or 20-25 c to detect the fungi.

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 Acc… to UNITED
STATES
PHARMACOPOEIA
1) WEIGHT VARIATION TEST (USP)

 Select the sample of 10 filled container and remove any labeling that might alter weight
during removing of the contents from the containers.

 Thoroughly clean and dry the outside of the container by a suitable means and weigh
individually.

 Remove the contents from each container by cutting, opening and washing with a suitable
solvent, taking care to retain the closures and any other parts of each container.

 Dry and again weigh each empty container together with its corresponding parts.

 The difference between weights is the net weight of the contents of each container.
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 The average net weight of contents of 10 containers is NLT the labeled amount.

 Net weight of contents of any single container is NLT 90% of the labeled amount,
where the labeled amount is MT 60 grams but NMT 150 grams.

 If the requirements are not met, determine the net weight of the contents of 20
additional containers.

 The average weight of the contents of 30 containers is NLT the labeled amount and
the net weight of contents of NMT 1 container of the 30 containers is
1)NLT 90% of the labeled amount, where the labeled amount is 60 grams or less.
2)NLT 95% of the labeled amount, where the labeled amount is MT 60 grams but
NMT150 grams.

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CONSISTENCY
Should be smooth, no solid particles.

IDENTIFICATION OF ACTIVE CONTENTS

Warm a saturated solution in water with Silver Ammonium Nitrate solution in a test tube.
Metallic Silver is deposited as a mirror on the sides of the tube.

ASSAY OF THE ACTIVE CONTENTS

For example: Salicylate ointment.
Dissolve 10 grams in a mixture of 20 ml of alcohol (95%) previous neutralized to phenol red
solution and 20ml of ether and titrate with 0.1N NaOH using phenol red solution as indicator.
1ml of 0.1N NaOH=0.01381 grams of salicylic acid.

MELTING POINT
Not less than 11C.

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SOLUBILITY
Should be soluble in 9 parts of water and 17 parts of boiling water, miscible with alcohol,
with solvent such as ether, chloroform or with volatile oils.

STERILITY TEST- (same as IP)

Method A- Membrane Filtration
Method B - Direct Inoculation

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GENERALISED
TESTS

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VISUAL EXAMINATION (ORGANOLEPTIC PROPERTIES)
CONTENT UNIFORMITY
HOMOGENEITY -Aabsence of gritty particles
RHEOLOGICAL STUDIES
MICROBIAL CONTENT
 Examined for P. aeruginosa and S. aureus.

IDENTIFICATION:
 Identity of drug and discriminate between compounds of closely related
structures
 Specific for drug substance.eg infrared spectroscopy, FTIR, or Raman
spectroscopic methods.
 Identification solely by a single chromatographic retention time may not be
specific, it should be supported with additional test.

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IN VITRO RELEASE TEST:
Ensure within lot and lot-to-lot uniformity. Determine the drugs release profile
Franz diffusion cell-for studying dissolution release through a cellophane membrane.
A dialysis membrane is loaded with 2 g of the medicated semisolid, suspended in a beaker
containing 100 ml of dissolution medium of pH 6.8, maintained at a temperature of 32ºC
and stirred at 100 rpm for one hour
Samples of the dissolution medium are withdrawn at time intervals to determine the amount
of the drug in solution. The release results are plotted as concentration versus time

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SPREADABILITY
 A sample of 1 g of semisolid was placed at the center of the glass plate (10 x 10 cm).
Another glass plate was placed over it carefully. Above the glass plates 2 kilogram weight
was placed at the center of the plate avoid sliding of the plate. The diameter of the
semisolid in centimeters was measured after 30 minutes. The Experiment Was Repeated
Three Times And The Average Was Calculated.

PH DETERMINATION
 Avoid irritation upon its application to the skin.
 GLASS ELECTRODE INSTRUMENT (pH meter).
 tested at the time of batch release and at designated stability time
 One gm of the topical preparation is dissolved in 100 ml of distilled water and stored for 2
hrs.
 pH measurement is done in triplicate and average values are calculated.
 For ointments it is difficult to check the pH because they are oily

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ACCELERATED STABILITY STUDIES
It is based on stressing the system, either by temperature or centrifugation

a- Effect Of Centrifugation
•Centrifugation can be used to predict long-term behavior of semisolids. Centrifugation at
3750 rpm for 5 hours is equivalent to the effect of gravity for one year.

b- Effect Of Freeze-thaw Cycling

•Semisolids are stored in an incubator at 50ºC for 48 hours and then transferred to a freezer
at -5ºC for 48 hours.

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ASSAY:
 A specific stability indicating assay should be used to determine strength of the product.
 In case if nonspecific method is justified, other supporting analytical procedure should be
used to achieve over all specificity.
 Stock solution is prepared and aliquots of different concentration were prepared by
suitable dilutions and their absorbance is measured and the drug content was calculated
using the equation, which was obtained by linear regression analysis of calibration
curve. [Y=mx+C]

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IMPURITIES:
 Process impurities
 Synthetic by-products
 Residual solvents
 Heavy metals and other inorganic or organic impurities.
 Degradation impurities should also be assessed and controlled.

ANTIMICROBIAL PRESERVATIVE CONTENT:

 Levels of antimicrobial preservative necessary to maintain the product’s microbiological
quality at all stages through its proposed usages and shelf life.

WATER CONTENT:
 Water activity test is generally formulation dependent, low water activity reduces
susceptibility to microbes.

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ANTIOXIDANT CONTENT:
 Acceptance criteria, level of antioxidant necessary to maintain product’s stability at
all stages through its proposed usage and shelf life.

PARTICLE SIZE:
 Topical products should be examined for evidence of particle size alteration (change
in size, shape, form, habit, or aggregation) of active drugs at the time of batch release
and at designated stability time.

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Stability Considerations:
Primary indications of instability in creams/ ointments are either discoloration or odor or a noticeable
change in consistency.

Instability Indications Of Creams:

Emulsion breakage (cracking of cream)
Crystal growth
Shrinking due to evaporation of water
Gross microbial contamination.

Instability Indications Of Ointments

Change in consistency and excessive “bleeding” (i.e., separation of excessive amounts
of liquid)
Formation of granules, or grittiness.

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TEST OF RATE OF ABSORPTION

 The ointment should be applied over a definite area of the skin by rubbing.
 At regular intervals of time, serum and urine samples should be analyzed for the quantity
of drug absorbed.
 The rate of absorption i.e., the amount of drug absorbed per unit time should be more.

TEST OF NON-IRRITANCY

 The bases used in the formulation of ointments may cause irritation or allergic reactions. Non
irritancy of the preparation is evaluated by patch test.
 In this test 24 human volunteers are selected. Definite quantity of ointment is applied under
occlusion daily on the back or volar forearm for 21 days.
 Daily the type of pharmacological action observed is noted.
 No visible reaction or erythema or intense erythema with edema and vesicular erosion should
occur. A good ointment base shows no visible reaction.
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TEST OF RATE OF PENETRATION
 Crucial in the onset and duration of action of the drug.

 Weighed quantity of the preparation should be applied over selected area of the skin for a
definite period of time. Then the preparation left over is collected and weighed.

 The difference between the initial and the final weights of the preparation gives the
amount of preparation penetrated through the skin and this when divided by the area and
time period of application gives the rate of penetration of the preparation.

 The test should be repeated twice or thrice.

 This procedure is tedious and not followed anymore.

 Using flow-through diffusion cell or Microdialys Method; the rate of penetration of the
preparation can be estimated.
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• Animal or human skin of definite area should be collected and tied to the holder present
in a diffusion cell.

• The diffusion cell is placed in a fluid bath.

• Measured quantity of the preparation is applied over the skin and the amount of drug
passed into the fluid is measured at regular intervals by analyzing the aliquots of fluid
using a Spectrophotometer

TEST OF RATE OF DRUG RELEASE

• A clean test tube is taken and the internal surfaces coated with the preparation as a thin layer.

• Saline or serum is poured into the test tube.

• After a certain period of time the saline is analyzed for the quantity of the drug.

• The amount of drug when divided by the time period gives the rate of drug release
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MICROBIAL METHOD

 Test Of Microbial Content

 Micro-organisms like Pseudomonas aeruginosa and Staphylococcus aureus may contaminate
the preparation and finally infect the skin.

 So ointments should be tested for the absence of such micro-organisms.

 Solutions of different samples of the preparation are made.

 Each sample is inoculated into separate volumes of 0.5 ml of rabbit's plasma under aseptic
conditions and incubated at 37oC for 1-4 hours.

 No formation of the clot in the incubated mass indicates the absence of the micro-organisms.

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 Test of preservative efficacy

 Using Pour plate technique the number of micro-organisms initially presents in the
preparation is determined.

 Solutions of different samples of the preparation

 Mixed with tryptone azolectin (tat) broth separately.

 Cultures of the micro-organisms are added into each mixture

Incubated.

 Then numbers of micro-organisms in each sample are counted on 7th, 14th, 21st and 28th
days of inoculation.

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FPQC TESTS
UNIFORMITY OF CONTAINERS:
Semisolid products may show physical separation during manufacturing process and shelf life. To
ensure the integrity of drug product, it is essential to evaluate the uniformity of the finished
product at the time of batch release and through its shelf life.
PRODUCTS PACKAGED IN TUBES:
Carefully cut off and open the side well of tube from bottom to the top in two flaps.
Inspect the exposed product visually for presence of phase separation, change in physical
appearance, texture, and other properties described in the product test for description.

Procedure 1:
1. Using single tube, remove samples from top, middle and bottom of the tube and
analyze drug substance quantitatively.
Evaluate the results using Acceptance criteria A. 50
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 2. If product fails, test three additional tubes from same batch and evaluate all test results using
Acceptance criteria B.

Procedure 2:
1. Using 2 tubes, remove samples from top, middle and bottom of the tube & analyze drug
substance quantitatively, evaluate the results using Acceptance Criteria A.
2. If product fails, test two additional tubes from same batch and evaluate all test results using
Acceptance Criteria B.

•Acceptance Criteria A: •Acceptance Criteria B:

All results are within product All results are within product
assay range and RSD is NMT 6%, or assay range and RSD of the 1, 2 (both)
as specified in specifications or in assay is NMT 6% or as specified in
compendial monograph. If RSD is ˃ product specifications or in
6%, use Acceptance criteria B. compendial monograph
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PRODUCTS PACKAGED IN CONTAINERS OTHER THAN TUBES:
 Sampling from top, middle and bottom of the jar by using a syringe.
 Test the samples according to the instruction outlined in products packaged in tubes.

AVERAGE FILLING WEIGHT

 In this test, the net weight or volume of the contents of the filled containers is determined.
 It is carried out to ensure that the product contains the proper content when compared
with the labeled amount.
 Weigh the intact container at the beginning of the analysis.
 After the analysis is completed, remove any remaining sample and weigh the empty
container.
 Calculate the weight of the product by difference.
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PACKAGING, STORAGE, AND LABELING:
Are packaged either in large-mouth jars or in metal or plastic tubes.
must be stored in well-closed containers to protect against contamination and in a cool place
to protect against product separation in heat.
When required, light-sensitive preparations are packaged in opaque or light-resistant
containers.
The USP directs that the labeling for certain ointments and creams include the type of base
used (e.g., water soluble or water insoluble).

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REFERENCES
 Indian Pharmacopoeia Ministry Of Health And Family Welfare, Published By
The Indian Pharmacopoeia Commission, Ghaziabad. Vol I II III, 2018 Edition,
 British Pharmacopoeia, 1993
 United States Pharmacopoeia.
 Review Article On Ointment, International Journal Of Pharmacy And
Pharmaceutical Research, Human Journals, September 2015 Vol.4, Issue:2

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 Thank
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