Quality control (QC) is a process by which entities review the quality of all factors involved in production. ISO 9000 defines quality control as "A part of quality management focused on fulfilling quality requirements In-process quality control tests are simply routine checks that are performed during production. They are those tests carried out before manufacturing process is completed to ensure that established product quality is met before they are approved for consumption and marketing. The function of in-process quality control is monitoring and if necessary adaptation of the manufacturing processes to ensure that the product conforms to its specifications. This may include control of equipment and environment also.

1. IPQC & FPQC
MANSI NARENDRASINH CHAUHAN
M.PHARM.

2. QUALITYCONTROLAND QUALITYASSURANCE
TOPIC: IPQC & FPQC (CREAMS,OPTHALMIC,PARENTRALS)
Presented by
Mansi Narendrasinh chauhan
M.Pharm
Pharmaceutical quality assurance
Guided by
Ms. Priya Shukla
Smt. BNB Swaminarayan Pharmacy College Salvav-Vapi

3. CONTENTS
• Introduction: IPQC
• Introduction: FPQC
• IPQC & FPQC for creams
I. Physical method
II. Microbiological method
III. Stability study
• IPQC & FPQC for parenterals &
ophthalmic
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4. INTRODUCTION: IPQC
• IPQC tests are performed at regular intervals (generally each 1 hr. later) during the
manufacturing process.
• The objectives of IPQC involve monitoring and alteration of the manufacturing
process if necessary with a vision to comply with the specifications. The control of
the environment or equipment may also be regarded as a part of in process control
(IPC).
• They should not carry any risk for the quality of product. In process testing
enables easier identification of problems. It sometime identifies a defective
product batch that can be corrected by rework, whereas once that batch has been
completed, this may not be possible.
• Failure to meet IPC specification indicates either those procedures were not
followed or some factors were out of control. Standard operating procedures
(SOPs) should be established in the pharmaceutical industry and followed that
describe the IPQCs and tests.
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5. INTRODUCTION: FPQC
• FPQCs are tests that are performed when the manufacturing process is completed
in order to check qualitative and quantitative characteristics along with test
procedures and their acceptable limits by which the finished product must comply
throughout its valid shelf-life.
• In order to determine the specifications of the finished product, the quality
characteristics related to the manufacturing process should be taken into account.
• An appropriate specification for each aspect of quality studied during the phase of
development and during the validation of the manufacturing process should be
determined. At least those aspects considered to be critical should be the object of
specifications routinely verified.
• The specification limits of the finished product at the time of batch release are set
by the marketing authorization applicant such that the specifications proposed at
the end of shelf-life are guaranteed and are established on the basis of a critical
detailed review of the data gathered from the batches analyzed.
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6. IPQC & FPQC FOR
CREAMS
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7. CREAMS
• Creams are semisolid viscous preparations which contain one or more drug
substances dissolved or dispersed in a suitable base and are used for topical
application on the skin or mucous membranes.
• They usually contain a water soluble base due to which they can be easily
removed from the skin.
• They are of softer consistency and have light weight in comparison to true
ointments when applied to the skin, creams leave no visible evidence of their
presence on the skin.
• Types of creams: Creams are of two types-
a) Aqueous creams (oil-in-water creams)
b) Oily creams (water-in-oil creams)
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8. EVALUATION OF CREAMS:
1. PHYSICAL METHODS
a. Test for Rate of Absorption:
Creams are those from which the drug initially moves into the deeper skin tissues
and finally into the systemic circulation. Such creams should be evaluated for the
rate of drug absorption. the cream is applied over a definite area of the skin and at
regular intervals of time, serum and urine samples are analyzed for the quantity of
drug absorbed.
b. Test for Irritancy:
The bases used in the formulation of creams may cause irritation or allergic
reactions. Irritancy of the preparation is evaluated by patch test. Mark an area
(1sq.cm) on the left-hand dorsal surface. The cream was applied to the specified
area and time was noted. Irritancy, erythema, edema, was checked if any for
regular intervals up to 24 hrs. and reported.
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9. 1. PHYSICAL METHODS
c. Test for Rate of Drug Release:
Method I
i. A clean test tube is taken and its internal surface is coated with the test preparation in
the form of a thin layer.
ii. Saline or serum is poured into the test tube.
iii. 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 II
i. Empty cream jar is filled with the test preparation and its mouth is closed with
cellophane.
ii. The jar is placed in a water bath in an inverted position for a definite period of time.
iii. The water is then analyzed for the drug content, from which the rate of drug release is
determined.
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10. 1. PHYSICAL METHODS
Method III
i. This method is suitable for drugs with bactericidal action.
ii. Five nutrient agar broth tubes are taken to which suitable medium is added.
iii. Staphylococcus aureus is inoculated into all the tubes.
iv. Under aseptic conditions, the inoculated medium is transferred into sterile petri
plates.
v. In the central portion of each plate, wells are made.
vi. Small quantity of preparation is added to these wells under aseptic conditions.
vii. All the plates are incubated after which the diameter of zone of inhibition of
microbial growth is measured.
viii.The average diameter of zone of inhibition is calculated and interpreted as the
rate of drug release.
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11. 1. PHYSICAL METHODS
d. Physical Properties:
The cream was observed for the color, odor and appearance.
e. pH:
The pH meter was calibrated with the help of standard buffer solution. Weigh 0.5
gm of cream dissolved it in 50.0ml of distilled water and its pH was measured
with the help of digital pH meter.
f. Spread ability test:
The cream sample was applied between the two glass slides and was compressed
between the two-glass slide to uniform thickness by placing 100 gm of weight for
5 minutes then weight was added to the weighing pan. The time in which the
upper glass slide moved over the lower slide was taken as a measure of spread
ability. Spread ability = m*l/t Where, m = weight tight to upper slide l = length
moved on the glass slide t = time take
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12. 1. PHYSICAL METHODS
g. Test for Rheological Properties:
Using Brookfield viscometer, the viscosity of the preparation is determined. The
viscosity of the preparation should be such that the product can be easily removed
from the container and easily applied onto the skin.
h. Test for Content Uniformity:
The net weight of contents of ten filled cream containers is determined. The
results should match with each other and with the labelled quantity. This test is
also called minimum fill test.
i. Saponification Value Take 2gm of the substance and reflux it with the 25ml of
0.5N alcoholic KOH for 30 minutes. Then add 0.1ml of phenolphthalein as a
indicator and titrate it with the 0.5N HCL. Saponification value = (b-a) *
28.05/W Where, a = volume of titrate (blank) b = volume of titrate (sample) w =
weight of substances in gram
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13. 1. PHYSICAL METHODS
j. Acid Value:
Take 10 gm of the cream dissolved in accurately weighed in 50 ml mixture of the
equal volume of alcohol and solvent ether. Then attached the flask with the
condenser and reflux it with the slow heating until the sample gets completely
dissolve then add 1 ml of phenolphthalein and titrate it with 0.1 N NaOH until it
gets faint pink color appears after shaking in 20 seconds. Acid value = n *
5.61/w Where, w = weight of the substances n = the number of ml in NaOH
required.
k. Dye Test:
The scarlet red dye is mixed with the cream. Place a drop of the cream on a
microscopic slide then covers it with a cover slip, and examines it under a
microscope. If the disperse globules appear red the ground colorless. The cream
is o/w type. The reverse condition occurs in w/o type cream i.e. the disperse
globules appear colorless.
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14. 2. MICROBIOLOGICAL METHODS
a. Test for Microbial Growth: Agar media was prepared then the formulated
cream was inoculated on the plate’s agar media by streak plate method and a
controlled is prepared by omitting the cream. The plates were placed in the
incubator and are incubated in 37˚C for 24 hours. After the incubation period,
the plates were taken out and the microbial growth were checked and
compared with the control.
b. Test for Preservative Efficacy:
Requirements
Microorganisms: Cultures of Aspergillus niger, Candida albicans, Escherichia
coli, Pseudomonas aeruginosa and Staphylococcus aureus, each containing
100000 to 1000000 cells/mL Medium: Tryptone Azolectin Tween (TAT) broth.
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15. 2. MICROBIOLOGICAL METHODS
Procedure
i. Using pour plate technique, the number of microorganisms initially present in the
preparation are determined.
ii. Solutions of different samples of the preparation are made and mixed with TAT
broth separately.
iii. All the cultures of the microorganisms are added into each mixture, under aseptic
conditions and incubated.
iv. The number of microorganisms in each sample are counted on 7th, 14th, 21st and
28th days of inoculation.
Microbial Limits
i. On the 14th day, the number of vegetative cells should not be more than 0.1% of
initial concentration. The viable yeasts and moulds should be below or equal to
initial concentration.
ii. On 28th day, the number of organisms should be below or equal to initial
concentration.
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16. 3. STABILITY STUDY
• The stability studies are carried out as per ICH guidelines.
• The cream is filled in the bottle and kept in humidity chamber maintained at:
30 ± 2°C/65 ± 5% RH
and 40 ± 2°C/75 ± 5% RH for 2 months.
• At the end of studies, samples are analyzed for all the evaluation parameters.
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17. IPQC & FPQC FOR
PARENTERALS &
OPTHALMIC
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18. STERILE DOSAGE FORM
Sterile Dosage Form:
• These are the products which are manufactured using sterilization or aseptic
processing conditions.
• There are two types of sterile dosage forms:
1. Parenteral preparation
2. Ophthalmic formulations
• The in-process quality control test includes the leakage and clarity testing.
• The quality control of finished product required the pyrogen and sterility
testing.
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19. LEAKAGE TEST
• Leakage test is employed to test the package integrity. Package integrity reflects its
ability to keep the product in and to keep potential contamination out”.
• It is because leakage occurs when a discontinuity exists in the wall of a package that
can allow the passage of gas under pressure or concentration differential existing
across the wall. Leakage test can be done by dye bath test.
Dye Bath Test:
The test container is immersed in a dye bath. Vacuum and pressure is applied for some
time. The container is removed from the dye bath and washed. The container is then
inspected for the presence of dye either visually or by means of UV spectroscopy. The
dye used may be of blue, green, yellowish-green color. The dye test can be optimized by
use of a surfactant and or a low viscosity fluid in the dye solution to increase the
capillary migration through the pores. The dye test is widely accepted in industry and is
approved in drug use. The test is inexpensive and is requires no special equipment
required for visual dye detection. However, the test is qualitative, destructive and slow.
The test is used for ampoules and vials.
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20. CLARITY TEST
• Clarity testing is carried out to check the particulate matter in the sample.
• In this test transparent particles or white particles observed against the black
background and the black or dark particles observed against the white
background.
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21. PYROGEN TEST
Limulus Amebocyte Lysate (LAL)
• Test The LAL Assay is an in vitro assay used to detect the presence and concentration
of bacterial endotoxins in drugs and biological products. Endotoxins, which are a type
of pyrogen, are lipopolysaccharides present in the cell walls of gram-negative bacteria.
• Pyrogens as a class are fever-inducing substances that can be harmful or even fatal if
administered to humans above certain concentrations.
• This test is based upon the gelling property of an enzyme, the limulus amebocyte
lysate extracted from the horse shoe crab, limulus polyphormus. The enzyme gels in
the presence of bacterial endotoxin and the degree of gelling is related to the amount of
endotoxin present. A no. of instrument is available for measuring the degree of gelling
of enzyme. The test can be used for quantifying the amount bacterial endotoxin present
and provide a better information regarding the quality of a product than rabbit pyrogen
test which is more of a qualitative test.
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22. STERILITY TEST
The tests for sterility are intended for detecting the presence of viable
microorganism in pharmaceutical preparation that is designed to be sterile. The
test is based on the principle that if micro-organism are placed in a medium that
provide optimum condition of nutrition, moisture, PH, aeration, temperature, they
can grow and their presence will be indicated by the presence of turbidity in clear
medium. Test for sterility may be carried out by one of the following two
methods.
1. Membrane Filtration Method
2. Direct Inoculation Method
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23. CONTENT UNIFORMITY & WEIGHT
• Determine the content of the active ingredient of each of 10 containers taken at
random.
• The preparation under examination complies with the test if the individual values thus
obtained are all between 85 and 115 percent of the average value.
• The preparation under the examination fails to comply with the test if more than one
individual value is outside the limits 85 to 115 percent of the average value or if any
one individual value is outside the limits 75 to 125 percent of the average value.
• If one individual value is outside the limits 85 to 115 percent but within the limits 75 to
125 percent of the average value, repeat the determination using another 20 containers
taken at random.
• The preparation under examination complies with the test if in the total sample of 30
containers not more than one individual value is outside the limits 85 to 115 percent
and none is outside the limits 75 to 125 percent of the average value. Limits for
uniformity of weight is given in Table 2.
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24. 3/28/2022 SMT. B.N.B SPC, salvav-vapi 24
PHARMACEUTICAL
FORMULATION
AVERAGE MASS
PERCENTAGE
DEVIATION (%)
Powders for parenteral
use
More than 40 mg 10
Powders for eye drops Less than 300 mg 10
Powders for eye lotions 300 mg or more 7.5
Table: 2 limits for uniformity of weight

25. EXTRACTABLE VOLUME
a) Single Dose Containers
Method I: Where the nominal volume does not exceed 5ml.
• Use 6 containers, 5 for the tests and 1 for rinsing the syringe used. Using a
syringe with appropriate capacity, rinse the syringe and withdraw as much as
possible the contents of one of the containers reserved for the test and transfer,
without emptying the needle, to a dry graduated cylinder of such capacity that
the total combined volume to be measured occupies not less than 40% of the
nominal volume of the cylinder. Repeat the procedure until the contents of the 5
containers have been transferred and measure the volume.
• The average content of the 5 containers is not less than the nominal volume and
not more than 115% of the nominal volume. Alternatively the volume of
contents in milliliter can be calculated as mass in grams divided by the density
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26. EXTRACTABLE VOLUME
Method II: Where the nominal volume is more than 5ml.
• Transfer the contents of not less than 3 containers separately to dry graduated
cylinders such that the volume to be measured occupies not less than 40% of
the nominal volume of the cylinder and measure the volume transferred.
• The contents of each container are not less than the nominal volume and not
more than 110% of the nominal volume.
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27. PARTICULATE MATTER IN INJECTIONS
• The preparations intended for parenteral use should be free from particulate
matter and should be clear when inspected visually.
• Two methods are described by USP according to the filled volume of the
product to be tested. For large volume parenteral (LVP's), a filtration followed
by microscopical examination procedure is used. For small volume parenterals
(SVP's) a light obscuration based sensor containing electronic liquid-borne
particle counter system is used.
• The USP standards are met if the LVP's under test contain NMT 50 particles per
ml of 10μ m, and NMT 5 particles per ml of 25μm in an effective linear
dimensional fashion.
• The USP standards are met if the SVP's under test contain NMT 10,000
particles per container of 10 μm, and NMT 1000 particles per container of
25μm in an effective spherical diameter.
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28. REFERENCE
• Uddin, Md Sahab, et al. "In-process and finished products quality control tests for
pharmaceutical capsules according to pharmacopoeias." Journal of Pharmaceutical
Research International (2016): 1-9.
• Amrutha, V., et al. "In-Process and Finished Products Quality Control Tests for Sterile
and Non Sterile Dosage Form." International Journal of Pharmaceutical Sciences
Review and Research 40 (2017): 206-214.
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