cream evalution and qc test for creams

1. Presented by Prakash Gupta
1st m pharm
Pharmaceutical Analysis
Submitted to Dr.C .Shreedhar
Professor and HOD
Pharmaceutical Analysis

3. i. Test for rate of absorption
ii. Test for non irritancy
iii. Test for rate of penetration
iv. Test for rate of drug release
v. Spreadability
vi. Test for content uniformity

4.  The cream is to 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.

5.  Some of the creams generally cause irritation to
the skin so, non-irritancy test should be carried
out.
 Non irritancy of the preparation is evaluated by
patch test.
 In this test 24 human volunteers are selected.
 Definite quantity of cream is applied daily on the
back for 21 days.

6.  Daily the type of pharmacological action observed
is noted.
 No visible reaction or erythma or intense erythma
with edema and vesicular erosion should occur.
 A good cream shows no visible reaction.

7.  The rate of penetration of a semisolid dosage form
is crucial in the onset and duration of action of the
drug.
 There are three methods for the determination of
rate of penetration.

8.  Weighed quantity of the preparation should be
applied over the selected area for a definite period
of time.
 Then the preparation left over is collected and
weighed.
 The difference between the initial and 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.
 This test should be repeated twice or thrice.

9.  Using flow through diffusion cell or micro-dialysis
method, the rate of penetration can be estimated.
 Animal or human skin of definite area should be
collected and tied to the holder present in the
diffusion cell.
 The diffusion cell is placed in a fluid bath.

10.  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
analzsing the aliquots of fluid using a
spectrophotometer.

11.  Carefully and completely fill three containers with
sample, without forming air bubbles.
 Level if necessary to obtain a flat surface. store
the samples at 25±0.5 for 24hrs,unless otherwise
prescribed.
 Apply a suitable shear to the samples for 5min.
 Place the sample on the base of the penetrometer.

12.  Verify that its surface is perpendicular to the
vertical axis of the penetrating object.
 Bring the temperature of the penetrating object to
25±0.5 & then adjust its position such that its tip
just touches the surface of sample.
 Release the penetrating object and hold it free for
5sec.clamp the penetrating object and measure
the depth of penetration.
 Repeat the test with the two remaining
containers.

13.  There are three methods by which the rate of drug
release from the cream base can be evaluated.
 Method 1 :
 A clean test tube is taken and the internal surface
is coated with the preparation as thin layer.
 Saline or serum is poured into the test tube.

14.  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.
Method 2 :
 Empty container is taken and filled with the
preparation and the mouth is closed with
cellophane.

15.  The container is placed in a water bath in an
inverted position for a definite period of time.
 Then the water is analyzed for drug content and
the rate of drug release is determined.

16.  It is determined by an apparatus suggested by
muttimer et al., which was suitably modified in the
laboratory and used for the study.
 It consists of a wooden block, which was provided
by a pulley at one end.
 A rectangular ground glass plate was fixed on this
block.
 An excess of cream(about 3gm) under study was
placed on this ground plate.

17.  The cream was then sandwiched between this
plate and another glass plate having the
dimension of fixed ground plate and provided with
the hook.
 A 1kg. Weight was placed on the top of the two
plates for 5min to expel air and to provide a
uniform film of the cream between the plates.
 Excess of the cream was scrapped off from the
edges.

18.  The top plate was then subjected to pull of 80gm.
 With the help of string attached to the hook and
the time(in sec)required by the top plate to cover a
distance of 10cm.
 A shorter interval indicates better spreadability.

19.  Select a sample of 10 filled containers and remove
any labeling that might be altered in weight while
removing the contents of the container.
 Clean and dry the outer surfaces of the containers
and weigh each container.
 Remove quantitatively the containers and wash
each empty container with a suitable solvent,
taking care to ensure that the closure and other
parts of the container are retained.

20.  Dry and again weigh each empty container
together with its parts which may have been
removed.
 The difference between the two weights of the
contents of the container.

21.  The average net weight of the contents of the 10
containers is not less than the labelled amount.
 The net weight of the contents of any single
container is NLT 91% and NMT 109% of the
labelled amount
 If the labelled amount is 50g or less then NLT
95%and NMT 104.5% of the labelled amount
 If the labelled is more than 50g then NMT 100%.

22.  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 and the net
wt of the containers of NMT 1 of the 20 containers
is less than 91% or more than 109% of the
labelled amount, where the labelled amount is
more than 50g but NMT 100g.

23.  This test is to ascertain that each tube is filled with
the minimum specified quantity. This test is also
called minimum fill test.

24. i. Test for microbiological content
ii. Test of preservative efficacy

25.  The micro organisms like pseudomonas aeruginosa
and staphylococcus aureus may contaminate
preparation and finally infect the skin.
 So semisolid dosage forms should be tested for the
absence of such micro organisms

26.  This test is also called as coagulase test.
 Solutions of different samples of preparations are
made.
 Each sample is inoculated into separate volume of
0.5ml of rabbit’s plasma under aseptic condition and
incubated at 37c for 1-4 hrs.
 No information of clot in the incubated mass indicates
the absence of the organism staphylococcus aureus.

27.  Requirements :
Micro organisms culture of aspergillus niger, candida
albicans, Escherichia coli, pseudomonas aeroginosa
and staphylococcus aureus each containing 1,00,000 to
100,000 cells/ml
Medium: Tryptophan azolecitin tween broth (TAT broth).

28.  Using a pour plate technique the number of micro
organisms initially present in the in the preparations are
determined.
 The solutions of different samples of preparation are
made and mixed with that broth separately.
 All cultures of micro organisms are added into each
mixture under aseptic condition. All the mixtures are
incubated.
 The number of micro organism in each sample are
counted on 7th , 14th , 21st and 28th days of inoculation.

29.  On the 14th day number of vegetative cells should not
be more than 0.1% of initial concentration.
 The viable yeast and moulds should be below or equal
to initial concentration.
 On the 28th day, the number of organisms should be
below or equal to initial concentration.

30.  Indian Pharmacopoeia 1996, volume-I, page no-
531, 311.
 United States Pharmacopeia, United States
Pharmacopeia/National Formulary
(USP24/NF19). 2000,
 REMINGTON’S; The Science and Practice of
Pharmacy 21st Edition; Volume1; Lippincott
Williams & Wilkins; 3rd Indian reprint 2009; page
no: 1028-1029.