Section-IN PROCESS QUALITY CONTROL and QUALITY CONTROL PDF

PHAR459
3. IN PROCESS QUALITY CONTROL

and QUALITY CONTROL MEASURES
IN PHARMACEUTICAL INDUSTRY
2
QUALITY CONTROL
quality control
Definition
 Quality control refers to the sum of all
procedures undertaken to ensure the identity
and purity of a particular pharmaceutical
product.
QUALITY CONTROL
THE IMPortance of quality and control of
quality
 Quality control is an essential operation of

the pharmaceutical industry.
 Drugs must be marketed as safe and
therapeutically active formulations
 Quality is the result of intelligent effort.
 The quality in the pharmaceutical industry has
become a very important and sensitive issue.
QUALITY CONTROL
quality
The goal of the pharmaceutical quality control

testing process is to produce satisfactory
results by investigating and monitoring the
quality of manufacturing pharmaceutical in
accordance with compendial standards and
specifications.
QUALITY CONTROL
quality
The quality of pharmaceutical products is essential to

assure the maximum level of patient’s satisfaction.
The most important criteria for quality of any drug in

dosage form are its safety, potency, efficacy, stability,
patient acceptability and regulatory compliance.
QUALITY CONTROL
quality
Counterfeit medicines;
The WHO defines a counterfeit drug as a product

that is with intent and illegally mislabelled with
respect to its identity and/or source.
Counterfeiting of medicinal products, active
pharmaceutical ingredients or product labels are
criminal offences, which may endanger patient
health.
QUALITY CONTROL
Counterfeit medicines may:
► contain no active ingredient
► contain the wrong active ingredient
► contain an incorrect quantity of the active ingredient
► be in low–quality packaging
► be manufactured using low–quality active ingredient
or excipient
► be manufactured under poor standards of good
manufacturing practice compliance.
QUALITY CONTROL
or excipient
QUALITY CONTROL
or excipient
 Quality control is an essential operation of
the pharmaceutical industry.
 New and better medicinal agents are being

produced at an accelerated rate. At the same
time more exacting and sophisticated
analytical methods are being developed for
their evaluation.
11
 Quality Control in the pharmaceutical
industry is required for :
 Raw Materials and API:

 Finished Products :
 Packaging Components :
12
 When the quality of any drug is given by industry, then
it is responsible for any variation from the standard.
 Quality Variation may occur due to any mistake during

the whole process i.e. from the reception of raw
material up to the final product in the packaged form.
 The risk of error increases as the material increases

and the method become very complicated..
13
 Improvement of the quality of production and
reduction in the production cost.
 Uniformity in the production and supply of standard

quality goods to consumers.
 Offering full return of the price paid by the

consumers and giving convenience and satisfaction to
consumers .
14
 Reduction in spoiled production and rejection from
consumers and dealers.
 Promotion of exports due to superior and standard

quality production.
 Reduction in inspection cost.
 Making products popular in market.
15
 Organoleptic tests
 Physical tests
 Physicochemical tests
 Microbiological tests
16
 Organoleptic tests:
are conducted to determine if the

pharmaceutical products can transfer tastes
or odors to the materials and components they
are packaged in
17
 Physical tests
 Physicochemical tests
 Microbiological tests
18
QUALITY CONTROL
To further enhance the effectiveness and
safety of the drug product after approval, many
regulatory agencies such as
the United States Food and Drug

Administration (FDA) also require that the drug
product be tested for its identity, strength,
quality, purity and stability before it can be
IN PROCESS QUALITY CONTROL
IPQC (in process
quality control)
These are checks that
are carried out before
the manufacturing
process is completed.
Rejected in-process
materials should be
identified and
controlled under a
quarantine system
IN PROCESS QUALITY CONTROL
IPQC (in process quality control)
 In process Quality Control, IPQC tests are mostly
performed within the production area.
 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.
 Failure to meet In process control specification
indicates either that procedure were not followed or
some factor were out of control.
 Standard operating procedures (SOPs) should be
established in the pharmaceutical industry and followed
that describe the IPQCs and tests
IPQC TESTS FOR VARIOUS DOSAGE
FORMS:
 I.P.Q.C TESTS FOR TABLETS
 IPQC TESTS FOR COATED TABLET
 IPQC TESTS FOR CAPSULES:
 I.P.Q.C TESTS FOR SYRUPS AND SUSPENSION
 I.P.Q.C TESTS FOR SEMI- SOLIDs
 I.P.Q.C TESTS FOR INJECTABLES

FORMS:
IPQC TESTS OF TABLETS

• Weight variation of tablets.
• Hardness of tablets.
• Thickness.
• Friability.
• Uniformity of content.
• Disintegration time.
• Dissolution test.
• Content of active ingredients.
FORMS:
IPQC TESTS FOR COATED TABLET

• Moisture content of dried granulation
• Granulation particle size distribution
• Blend uniformity
• Individual tablet/capsule weight
• Hardness
• Thickness
• Disintegration
• Impurity profile
FORMS:
IPQC TESTS FOR CAPSULES:

• Assay.
• Weight variation test.
• Disintegration time.
• Dissolution time.
• Moisture test.
• Iron test.
• Hardness and flexibility of shell.
• Loss on drying.
• Stability test at different temperature.
QUALITY CONTROL EQUIPMENTS
FORMS:
Drug Content Determination
A physically sound tablet may not produce the desired

effects. To evaluate a tablet potential for efficiacy, the
amount of drug per tablet needs to be monitored from
tablet to tablet and batch to batch, and a measure of
the tablets ability to release the drug needs to be
ascertained.
FORMS:
Moisture Content of granules

Granules should possess sufficient strength to
withstand normal handling and mixing processes
without breaking down and producing large amounts of
fine powder.
On the other hand, some size reduction during
compaction into tablets is desirable to expose the areas
of clean surface necessary for optimum bonding to take
place so moisture content is the very important factor
for producing good pharmaceutical product.
FORMS:
Assay of active ingredient
In a tablet an active ingredient is present which

is called active pharmaceutical ingredient
(A.P.I).
So to prepare the tablet assay has to be done
to produce good finished product.
FORMS:
Hardness test
The monitoring of tablet hardness is especially
important for drug products that possess real
or potential bioavailability problems that are
sensitive to altered dissolution release profiles
as a function of the compressive force
employed .
FORMS:
Disintegration test
A generally accepted maximum is that drug to

be readily available to the body, it must be in
solution.
For most tablets, the first important step
towards solution is break down of the tablet
into smaller particles or granules, a process
known as disintegration.
QUALITY CONTROL
FORMS:EQUIPMENTS
I.P.Q.C TEST FOR SYRUPS AND SUSPENSION
a) Drug contents determination.

b) Assay of active ingredients.
c) pH.
d) Weight per ml.
e) particle size
FORMS:
Drug content determination
Determination of drug content in suspension and

syrups are important because their
concentration has to be sufficient itself that it
produce the pharmacological action.
A suspension is much prescribed to pediatrics

so their concentration has to be sufficient not
to less not to large.
FORMS:
Assay of active ingredient
Active ingredient means pure drug present in

the product .An assay of active ingredient must
be done because it is the only which is
responsible for pharmacological action and in
syrups and suspension a small and fine particles
are included in syrups and suspension
FORMS:
pH of the product
pH affects the stability of the product so

before filling and after filling of suspension and
syrups pH has to be checked out for
consistency of the product.
FORMS:
Particle size
In suspension and syrups a solute particles is

dispersed in a suitable solvent so particle size
becomes the important factor for the
suitability of the product and all the particles
has to be of same size and shape for proper
dispersing in the solvent
FORMS:
I.P.Q.C TEST FOR SEMI- SOLIDs

b) Assay of active ingredients.
c) Uniformity and homogeneity test.
d) Viscosity and specific gravity test.
e) Filling test.
FORMS:
Homogenecity test
The semi-solid preparations require further

treatment are transferred or pumped to the
proper homogenizer, the selection of which is
governed by the degree and rate of shear
stress required.
FORMS:
Viscosity and Specific gravity test
Once the desired semi-solid preparation have

been chosen, a consistency that provides the
desired stability and has appropriate flow
characterstics must be attained. For emulsion it
is routinely observed that the building up of
viscosity in a freshly prepared emulsion requires
some time.
FORMS:
I.P.Q.C TEST FOR INJECTABLES

b) Clarity test.
c) pH.
d) Pyrogen test.
e) Sterility test.
f) Leakage test.
g) Check up of particulate matters.
FORMS:
Pyrogen test
The presence of pyrogenic substance in

parenterals is determined by a qualitative
biologic test based on the fever response of
the rabbits.
Rabbits are used as test animal because they
show a physiologic response to pyrogens similar
to that of human beings. If a pyrogenic
substance is injected into the vein of a rabbit,
an elevation of temperature occurs in a period
of three hours.
FORMS:
Sterility test
All products labeled “sterile” must pass through
sterility test, having been subjected to an
effective process of sterilization
.
With a terminal methods of sterilization of a
parenteral product, particularly steam under
pressure, a probability of no more than one
sterile unit in a million is readily achievable.
FORMS:
Leaking test
Ampules are intended to provide sealed

container for a single dose of a product,
thereby completely barring any interchange
between the contents of the sealed ampule and
its environment.
Should capillary pores or tiny cracks be
present, microorganisms or other dangerous
contaminants may enter the ampule or the
contents may leak to the outside and spoil the
appearance of the package.
FORMS:
Clarity test
Clarity is the relative term, the meaning of which is

markedly affected by the subjective evaluation of the
observer. Unquestionly a clean solution having a high
polish conveys to the observer that the product is of
exceptional quality and purity.
This clarity test is performed in industry by visual

inspection machine by the light baffles against
reflection into the eyes, and views against a black and
white background, with the contents set in motion with
a swirling action
PHARMACOPOEIAL
QUALITY CONTROL TESTS
PHARMACOPOEIAL QUALITY CONTROL TESTS:
According to BRITISH PHARMACOPOEIA QUALITY
CONTROL TEST
FOR ALL TABLETS:
• Content of active ingredients
• General Appearance
• Disintegration (coated, uncoated & effervescent
tablet)
• Uniformity of weight
• Uniformity of content
• Dissolution test
• Uniformity of dispersion (for dispersible tablet)
• Tablet diameter
QUALITY
QUALITY CONTROL
CONTROL EQUIPMENTS
TESTS FOR TABLETS:
General Appearance:
 Size, shape, and thickness:
This is important to facilitate packaging and to decide
which tablet compressing machine to use.
 Organoleptic properties:
include color and odor of the tablets.
 Weight uniformity and content uniformity:

This test is to ensure that every dosage form contains
equal amount of drug substance i.e. active
pharmaceutical ingredient within a batch.
PHARMACOPOEIAL QUALITY CONTROL
QUALITY
QUALITY CONTROL
CONTROL EQUIPMENTS
TESTS FOR TABLETS:
TESTS:
QUALITY CONTROL TESTS FOR TABLETS:
 Dissolution test:
Drug should be released from tablet in a controlled and
reproducible way.
 Weight variation, thickness & diameter:
The appearance of tablet should be elegant & its
weight, size & appearance should be consistent.
 Hardness & friability: The tablet should show
sufficient mechanical strength to withstand fracture
& erosion during manufacture & handling.
OFFICIAL STANDARDS AS PER B.P. /I.P./
U.S.P.:
comparison of different pharmacopoeial quality control

tests :
BRITISH PHARMACOPOEIA:
FOR ALL TABLETS:
Content of active ingredients
Disintegration
Uniformity of content
Labeling
U.S.P.:
 Uncoated tablet:
- Disintegration test
- Uniformity of weight
 Effervescent tablet:
 Coated tablet:
U.S.P.:
 Gastro resistant tablet:
 Modified release tablet:
- Uniformity of weight.
 Dispersible tablet:
- -Disintegration test
- - Uniformity of dispersion
- - Uniformity of weight
U.S.P.:
INDIAN PHARMACOPOEIA :
 Uncoated tablet:
-Uniformity of container content
-Content of active ingredient
-Uniformity of weight
-Uniformity of content
-Disintegration test
 Enteric coated tablet:
U.S.P.:
 Dispersible tablet:
-Uniformity of dispersion
-Disintegration
 Soluble tablet:
 Effervescent tablet:
-Disintegration/ Dissolution / Dispersion test
U.S.P.:
UNITED STATES PHARMACOPOEIA:
Physical tests applicable to tablet formulation:
-Bulk density /Tapped density of powder
-Powder fineness
-Loss on drying
-Tablet friability
-Dissolution test
-Drug release testing
-Uniformity of dosage form
-Container permeation test
-Labeling of inactive ingredients
U.S.P.:
OFFICIAL AND UNOFFICIAL TESTS:
 Official Tests:
uniformity of active ingredient,
disintegration,
dissolution.
 Non-Official Tests:
Hardness,
friability.
U.S.P.:
1-NON OFFICIAL TESTS:
 HARDNESS (CRUSHING STRENGTH):
It measures crushing strength property defined as
compressional force applied diametrically to a tablet
which just fracture it.
Why do we measure hardness?

 To determine the need for pressure adjustments on
the tableting machine.
 Hardness can affect the disintegration.
U.S.P.:
Results:
 In general, if the tablet hardness is too high, we first

check its disintegration before rejecting the patch.
And if the disintegration is within limit, we accept the
patch.
 If hardness is high + disintegration is within time we

accept the batch .
U.S.P.:
FRIABILITY:
The tablet may well be subjected to a tumbling motion.
For e.g: Coating, packaging, transport, which are not
severe enough to break the tablet, but may abrade the
small particle from tablet surface.
To examine this, tablets are subjected to a uniform
tumbling motion for specified time and weight loss is
measured.
U.S.P.:
OFFICIAL TESTS:
DISINTEGRATION:
It is the time required for the tablet to break into
particles, the disintegration test is a measure only of
the time required under a given set of conditions for a
group of tablets to disintegrate into particles
U.S.P.:
Uniformity of Active Ingredients:
 It is measured to ensure a constant dose of drug
between individual drugs
 Traditionally, dose variation between tablet is tested
in two separate tests namely
A) Weight variation
B) Content uniformity
U.S.P.:
DISSOLUTION TEST:
 The release of drug from the tablet into solution per
unit time under standardize condition is called
dissolution test.
 Media used in dissolution testing may be purified
water, simulated gastric fluid, simulated intestinal
fluid or others. Organic solvents are not
recommended.
 The most commonly used are USP apparatus I
(basket) and USP apparatus II (paddle).
Quality control of capsules
Whether capsules are produced on a small scale or

large scale all of them are required to pass through
certain tests i.e., quality control tests to test the quality
of the finished product.
Quality control tests are
divided into
PHYSICAL TEST CHEMICAL TEST

• Disintegration test • Dissolution test
• Weight variation • Assay
• Content uniformity
• Moisture permeation test
Quality control tests for
parenterals
parenterals
Uniformity of content
Test for volume of liquid
Test for pyrogen
Test for sterility
Clarity of solution
Uniformity of weight
Test for bacterial endotoxin
Leakage test
30 sterile units are selected from each batch.
• The weight of 10 individual sterile units is noted and the content is removed
from them and empty individual sterile unit is weighed accurately again.
• Then net weight is calculated by subtracting empty sterile unit weight from
gross weight.
• The dose uniformity is met if the amount of active ingredient is within the range
of 85-115.0% of label claim. UNIFORMITY OF CONTENT
parenterals
 Relative standard deviation is equal to or less than
6.0%.
 If one unit is outside the range of 85-115.0%, and none
of the sterile unit is outside the range of 75-125.0% or
if the relative standard deviation of the resultant is
greater than 6.0% ,or if both condition prevail, an
additional 20 sterile unit should be tested.
 The sterile units meet the requirements if not more
than one unit is out side the range of 85-115%, no unit
is outside the range of 75-125.0% and the calculated
relative standard deviation is 7.8%.
TEST FOR VOLUME OF LIQUID
Test applies to liquid supplied in single dose ,

only part of the content is used
Empty the contents of one container&
determine the volume of contents
 Emulsions & suspensions shake the container
before the determination
The volume is not less than the amount stated
on the label.
Test for sterility
Sterility is
defines as
freedom from
the presence of
viable
microorganism
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.
 Which is the flow of matter through the barrier
itself.
1. using methylene blue solution
2. spark test
Leakage test
Leakage Test (with methylene blue solution):

 The ampoules are immersed in vacuum chamber
consisting of 1% methylene blue solution
 A vacuum of about 27 inch Hg is created for about 15
to 30 min.
 This causes the solution to enter the ampoules with
defective sealing.
 The vacuum is released and ampoules are observed.
 If a leakage is present, the solution in the ampoules
appear blue color.
Leakage test
Leakage Test machine:

Leakage test
Spark Test:
 The machine uses high precision electrodes to inspect
the full circumference of the containers, including the
closure zone.
 All containers are presented individually to the
electrodes.
 Any moisture that has penetrated through capillary
forces in a crack, pinhole or just weak glass is
registered as a change in resistance.
 All products with a measured voltage higher than a
defined maximum value are separated from the good
products.

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PHAR459

3. IN PROCESS QUALITY CONTROL

 Quality control is an essential operation of

The goal of the pharmaceutical quality control

The quality of pharmaceutical products is essential to

The most important criteria for quality of any drug in

The WHO defines a counterfeit drug as a product

 New and better medicinal agents are being

 Raw Materials and API:

 Quality Variation may occur due to any mistake during

 The risk of error increases as the material increases

 Uniformity in the production and supply of standard

 Offering full return of the price paid by the

 Promotion of exports due to superior and standard

 Reduction in inspection cost.

 Making products popular in market.

are conducted to determine if the

the United States Food and Drug

 IPQC TESTS FOR COATED TABLET

 IPQC TESTS FOR CAPSULES:

 I.P.Q.C TESTS FOR SYRUPS AND SUSPENSION

 I.P.Q.C TESTS FOR SEMI- SOLIDs

 I.P.Q.C TESTS FOR INJECTABLES

IPQC TESTS OF TABLETS

IPQC TESTS FOR COATED TABLET

IPQC TESTS FOR CAPSULES:

Drug Content Determination

A physically sound tablet may not produce the desired

Moisture Content of granules

In a tablet an active ingredient is present which

A generally accepted maximum is that drug to

I.P.Q.C TEST FOR SYRUPS AND SUSPENSION

a) Drug contents determination.

Determination of drug content in suspension and

A suspension is much prescribed to pediatrics

Active ingredient means pure drug present in

pH affects the stability of the product so

In suspension and syrups a solute particles is

a) Drug contents determination.

The semi-solid preparations require further

Once the desired semi-solid preparation have

a) Drug contents determination.

The presence of pyrogenic substance in

Ampules are intended to provide sealed

Clarity is the relative term, the meaning of which is

This clarity test is performed in industry by visual

 Weight uniformity and content uniformity:

comparison of different pharmacopoeial quality control

Why do we measure hardness?

 In general, if the tablet hardness is too high, we first

 If hardness is high + disintegration is within time we

Whether capsules are produced on a small scale or

PHYSICAL TEST CHEMICAL TEST

30 sterile units are selected from each batch.

Test applies to liquid supplied in single dose ,

 Leakage test is employed to test the package

Leakage Test (with methylene blue solution):

Leakage Test machine:

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