The document provides information on analyzing raw materials, packaging materials, and finished products for quality control in pharmaceutical manufacturing. It discusses testing of raw materials upon receipt, proper storage and labeling, and sampling procedures. It also describes in-process quality control testing for tablets and capsules, including tests for hardness, friability, thickness, disintegration, weight variation, content uniformity, and dissolution. Specific pass/fail criteria are provided for each test. Leak testing procedures for blister and strip packaging are also summarized. The document aims to ensure quality of pharmaceutical products through rigorous analysis and quality testing at various stages of production.

1. UNDER THE GUIDANCE OF
PROF. GURPAL SINGH
Analysis of Raw materials
, Packaging materials &
Finished products and
IPQC of Tablets &
capsules
SATYAM RAJ
2nd sem , M.Pharm, PA & QA
University Institute of Pharmaceutical Sciences
Panjab University , Chandigarh

2. Index
 Analysis of raw materials
 Analysis of finished products
 Analysis of packaging materials
 IPQC
 Purpose of IPQC
 Types of IPQC
 IPQC test for Tablets
 IPQC test for Capsules
 Reference

3. RAW MATERIALS
 In case of R.M. following points should be considered.
I. Supplier/Manufacturer of the received material should have his name listed in companies
approved vendors list. Such list should be available with the receiving department.
II. All R.M. and other related materials should be checked for following things, after receiving:
(a) Name of the manufacturer/supplier.
(b) Name of the product.
(c) Batch numbers
(d) Date of manufacture and date of expiry.
(e) Quantity received and number of containers or packages.
(f) Condition of containers and materials.
All containers should be cleaned externally and damages if any, should be informed to Q.C.
department. The cleaned containers should be protected from contamination during storage.
The materials received should be taken into account only after all the relevant documents are
available. (e.g. bills, invoice, customs or excise gate passes, certificate of analysis etc.)

4. III. Sampling of these received materials should take place in specific sampling
booths by Q. C. persons only and containers should be labelled accordingly.
These materials shall be stored in sampled material quarantine.
IV. All received materials must be properly identified with their status (e.g. received,
sampled, approved, rejected, to be returned back etc.) labels and material
identifications like. product name, batch number, code number, sterility status etc.
V. Materials in the storage area should be appropriately labelled. Labels should bear at
least the following information:
(a) The name and internal code number of the product.
(b) The batch number given by the supplier/manufacturer and given by the receiver
after analysis and release.
(c) Status of the material e.g. quarantine, on test, released, rejected,
returned , recalled etc.
(d) Retest and expiry date of the product.
(e) Appropriate special storage conditions e.g. store at low temperature, low
humidity away from direct light etc. or sterile material etc. should be clearly
mentioned.

5.  In fully computerized storage system, all the above information may not be legible
on the container label, in such case a practice of referring to the computerized
information should be followed.
vi. Only materials released by Q. C. department and within their shelf-life should be
used.
vii. Materials should be dispensed only by designated persons, following a written
procedure, to ensure that the correct materials are accurately weighed or measured
into clean and properly labelled container.
The word correct material in above paragraph refers to the following points:
(a) Correct name and category (I.P./B.P/U.S.P. etc.) of the material.
(b) Correct A. R. number.
(c) Correct weight/measure.
(d) For correct B.No. of the product. And the check recorded. Conspicuously labelled.

6. viii. Each dispensed material and its weight or volume should be independently checked.
ix. Materials dispensed for each batch of the final product should be kept together and
conspicuously labelled as or such.
x. All dispensed materials must be recorded in a register in chronological order of date and
time. This record should have at least the following information:
(a) Name of the product and B. No. for which the material is dispensed.
(b) Time and Date of starting and completion of the dispensing activity.
(c) Name of the weigher and checker of the dispensed materials.
 Normally a Q.C. person should check the weighing's independently.
The production supervisor will check it at the time of processing the batch.
 Documents Required
1. List of approved vendors with materials,
2. List of materials classified according to storage conditions,
3. SOP on sampling, storage and dispensing of materials,
4. Register of sampling and dispensing activities.

7. Raw Material
Check R.M Batch no. expire
date
Received by
manufacturer
R.M takes place
by Q.C person
Rejected
Batch
Finished
Product
Intermediate
(Bulk Product)
Mfg. of
R.M
Recalled
Product
Return good
Diagrammatic Presentation

8. FINISHED PRODUCTS
 Finished products are products which are in the marketable pack.
These products should be held in quarantine until their final release, after which
they should be stored as usable stock under conditions established by the
manufacturer.
Each batch of the finished product should be tested as per laid down testing
procedure against its specifications and then only released for distribution or
sale.
Products failing to meet the established specifications or any other relevant
quality criteria should be rejected. Reprocessing may be performed, if feasible,
but the reprocessed product should meet all specifications and other quality
criteria prior to its acceptance and release.
Documents Required
(i) SOP on releasing of the finished product.
(ii) SOP on reprocessing of rejected finished product.

9. Packaging materials
 Packaging materials are divided into following categories :-
1. Primary Packaging Materials :- Materials which comes in direct contact with the
medicinal product. e.g. bottles, WAD , ampoules, vials, foils, blister etc.
2. Secondary Packaging Materials:- Materials which come in contact with the primary
packaging materials and give support to primary package .
e.g. labels, carton, Corrugated fiber board , leaflets etc.
3. Tertiary Packaging Materials:- Its is used for bulk shipping and transporting .
e.g. Brown cardboard boxes , wood pellets and shrink wraps
 While handling all these materials following points should be kept in mind.
(i) The purchase, handling and control of primary and printed packaging materials shall
be as for raw materials.
(ii) Tertiary packaging materials should be stored securely in lock and key system to
avoid unauthorized access. Cut labels and other loose printed materials should be
stored and transported in separate closed containers so, as to avoid mix-ups. A
detailed SOP should be available for dispensing of packaging materials. Only
authorized persons should do dispensing and make records of all the activities.
(iii) Each delivery or batch of printed or primary packaging materials should be given a
specific reference number or identification mark.

10. iv. Outdated and obsolete primary or printed packaging materials should be destroyed by
suitable and approved method of destruction and records maintained. The destruction of
printed packaging materials should be done under the direct supervision of a responsible
or Q. A. person.
v. All products and packaging materials to be used should be checked on delivery to the
packaging department for quantity, identity, and conformity with the packaging
instruction. Quantitative records of printed packaging materials should be maintained to
the last unit of counting. All audit and inspecting authorities are very much rigid and strict
on this issue; since unaccounted printed packaging materials have a potential danger of its
misuse.
vi. Access to all storage areas should be limited to authorized personnel only.
vii. A separate sampling room should be provided for sampling of primary packaging
materials, which should be a fairly clean area.
Documents Required
(i) A classified list of all packaging materials e.g. primary, secondary, tertiary and other
materials.
(ii) A list of approved vendors along with names of materials.
(iii) Sampling and dispensing register in chronological order.
(iv) A list of materials based on their storage conditions

11. IPQC ( In-Process Quality Control )
 IPQC means controlling the procedures involved in manufacturing of
the dosage forms starting from raw material purchase to dispatch of
the quality product in ideal packaging.
 It monitors all the features of the product that may affect its quality and
prevent errors during processing.
 It is the activity performed between QA and QC.

12. Purpose
 To ensure detectable and significant human errors .
 Equipment failure and idiosyncrasies .
 Abnormal interpretation .
 Adoption of given procedures.

13. Types of IPQC tests
Identity Tests
Quality tests
Purity tests
IPQC tests
Physical and Chemical Biological & Microbiological
Potency tests

14. Physical and chemical
tests
 Identity tests : These tests are qualitative chemical methods used to confirm
the actual presence of compound . For ex. Colour formation , precipitation
 Quality tests : These tests are the physical methods used to measure
accurately the characteristic properties of drug . For example : Absorbance ,
refractive index .
 Purity tests : Purity tests are designed to estimate the levels of all known and
significant impurities and contaminants in the drug substance under
evaluation . For example : Tests for clarity of solution , acidity / alkalinity
 Potency tests : Potency tests are assays that estimate the quantity of an active
ingredient in drug .

15. Biological and microbiological tests
 It includes macro and micro biologic assays and tests for safety , toxicity ,
pyrogenicity , sterility , antiseptic activity and antimicrobial preservative
effectiveness tests . Biological testing of drugs can be qualitative or
quantitative in nature .
 It utilizes intact animals , animal preparations , isolated living tissues.

16. IPQC test for Tablets :
 Hardness
 Friability
 Thickness
 Disintegration
 Weight variation
 Content uniformity
 Dissolution
 Leakage testing for strip and blister packaging

17. Hardness (crushing strength):
 It is the load required to crush the tablet when placed on its edge.
 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 then accept the batch .

18. Hardness (crushing strength):
 Some of devices used to test tablet hardness are :
 Monsanto tester
 Strong-cobb tester
 Pfizer tester
 Erwica tester

19. Friability:
 It is the tendency of tablets to powder, chip, or fragment and this can
affect the elegance appearance, consumer acceptance of the tablet, and
also add to tablet’s weight variation or content uniformity problems.
 Friability is a property that is related to the hardness of the tablet.
 An instrument called friabilator is used to evaluate the ability of the
tablet to withstand abrasion in packaging, handling, and shipping.
 Commonly used friabilator in industries is Roche Friabilator.

20. Procedure :
1. Weigh 20 tab altogether = W1
2. Put these tablets in the friabilator and adjust the instrument at 100 rpm
(i.e. = 25 rpm for 4 min)
3. Weigh the 20 tablets = W2
4. Friability (% loss) = It must be less than or equal to 1%.
Friability (%loss) = W1 –W2 /100
W1 = Initial weight of 20 tablets
W2 = Weigh 20 tablets after 100 rotation

21. THICKNESS TEST:
 The thickness of a tablet depends on the upper and lower punches at the
moment of compression.
 It can be tested using vernier calipers.
 The range varies with +/- 5.0%.

22. DISINTEGRATION TEST :
 The disintegration USP device uses 6 glass tubes that
are 3 inches long open at the top and held against a
10mesh screen at the bottom end of the basket rack
assembly.
 One tablet is placed in each tube , and the basket rack is
positioned in a 1 L beaker of water, simulated intestinal
fluid at 370 c ± 20 c , such that the tablets remain 2.5
cm from the bottom of the beaker.
 Frequency of basket is 28-32 cycles/min .
 The test is done on 6 tablets and the test is passed
when all the 6 tablets disintegrate.

24. Limit for Disintegration test
 For uncoated tablets: If one or two tablets from the 6 tablets fail
disintegrate completely within 30min repeat the same test on another 12
tablet. (i.e. the whole test will consume 18 tablets). Not less then 16
tablets disintegrate completely within the time if more then two tablets
(from the 18) fail to disintegrate, the batch must be rejected.
 For Coated tablets: If one or two tablets fail to disintegrate, repeat on 12
tablets. So 16 tablets from the 18 must completely disintegrate within the
time >>if two or more not disintegrated the batch is rejected.
 For Enteric coated tablets: If one or two tablets fail to disintegrate,
repeat this test on another 12 tablets. So 16 tablets from 18 should
completely disintegrate. If more than two fail to disintegrate the patch
must be rejected.

25. Weight variation Test :
 The volumetric fill of the die cavity determines the weight of the compressed
tablet . The weight of the tablet is the quantity of the granulation that contains
the labeled amount of the therapeutic ingredient.
 After the tablet machine in operation the weights of the tablets are routinely
checked to ensure that proper tablet weights are made.
Procedure :
1. Take 20 tablets
2. Determine the individual weights of each tablets

26. Weight variation Test :
3. Take average weights of 20 tablets .
4. Compare the individual weight of tablets with avg weight.
5. Not more than 2 tablets should deviate from avg weight by percent
deviaton and none should deviate more than twice the percentage.
Limits according to U.S.P
·Weight of tablet 130 mg or less then % deviation = ±10%
·Weight of tablet 130-324 mg then %deviation = ±7.5%
·Weight of tablet 324 mg or more then %deviation = ±5%

27. Content uniformity :
Procedure :
 In this test 30 tablets are randomly selected for the sample and atleast 10 of
them assayed individually .
 9 of the 10 tablets must contain not less than 85% or more than 115 % of
labeled drug content.
 10th tablet may not contain less than 75% or more than 125% of labeled
content .
 If this conditions are not meet the tablet remaining from the 30 must be
assayed individually and none may fall outside 85 to 115 % .

28. Dissolution testing :
 Dissolution is performed to check the
percentage release from the dosage forms
from the tablet.
 When tablet disintegrate it breaks down into
small particles which offers a greater surface
area to the dissolving media and drug will
dissolve .

29. Dissolution testing :
 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 ( as specified in the
monograph ) contained in a 100ml flask.
 The flask is maintained at 370c ± 0.50c by a constant temperature bath.
 The motor is adjusted to turn at the specified speed, and samples of the
fluid are withdrawn at intervals to determine the amount of drug in
solution.

31. Limits of Dissolution testing :

32. Leak testing for Strips and Blister packing :
 Take the required number of strips / blisters as mentioned in annexure .
Check the quality of strips/ blisters for any damages.
 Tie the collected strips / blisters with a rubber band.
 Ensure that all strips / blisters are dipped in water and close the lid.
 Connect opening of the desiccator to the vacuum pump.
 Apply a vacuum of 300 mm of Hg and close the knob of the desiccator.
 Keep the vacuum for 30sec.

33. Leak testing for Strips and Blister packing :
 Release the vacuum by opening the knob of the desiccator slowly and open the
lid remove the strips / blisters.
 Wipe out the traces of water from the strips / blisters by using lint free duster .
 Open the pocket of strips by using scissors to remove the tablets / capsules.
 Open the blisters manually.
 Check for any traces of water inside the strips / blisters.
 Number of tablets or capsules, which have become wet , should not be more
than 1%.

34. IPQC TEST FOR CAPSULE :
 Appearance
 Size and Shape
 Disintegration Test
 Moisture permeation test
 Bloom strength of gelatin
 Content uniformity

35. Appearance :
 Capsules produced on a small or a large scale should be uniform in
appearance.
 Visual or electronic inspection should be undertaken to detect any flaws
in the integrity and appearance of the capsule.
 Evidence of physical instability is demonstrated by gross changes in
appearance, including hardening or softening, cracking, swelling,
mottling, printing mistake or discoloration of the shell.
 Defective capsules should be rejected.

36. Size and Shape:
 Hard capsules are made in a range of sizes, the standard industrial
ones in use today for human medicines range from size from 000 (the
largest, 1.40 ml) to 5 (the smallest, 0.13 ml) are commercially available.
 Soft gel capsules are available in variety of shapes such as spherical
(0.05–5 ml), ovoid (0.05–7 ml), cylindrical (0.15– 25 ml), tubes (0.5–0 ml),
pear (0.3–5 ml) etc .

37. Disintegration test:
 It is same as the test for tablets.
 If the capsules float on the surface of the medium, a disc may be added.
 If the capsules adhere to the disc, attach a removable piece of stainless steel
woven gauze with mesh aperture of 2.0 ± 0.2 mm to the upper plate of the
basket rack assembly and carry out the test omitting the discs.
 Operate the apparatus for 30 min unless otherwise directed.
 For hard gelatin capsule 30 min and for soft gelatin capsules 60 min is required.

38. Disintegration test:
 If any capsules fails to disintegrate, repeat the test on further 6 capsules.
 In the repeat test , if any capsule have not disintegrated , again repeat on 6
capsules replacing water in the vessel with 0.1 M hydrochloric acid or artificial
gastric juice .
 The capsule pass the test if all the 6 have disintegrated.

39. Moisture permeation test :
 The degree and rate of moisture penetration is determined by
packaging the dosage unit together with a color revealing desiccant
pellet .
 Expose the packaged unit to known relative humidity over a specified
time.
 Observe the desiccant pellet for color change.
 Any change in color indicates absorption of moisture .
 By measuring pre test weight and protest weight of pellet, amount can
be calculated.

40. BLOOM STRENGTH OF GELATIN :
 Bloom is a test to measure the strength of a gel or
gelatin. The test was originally developed and patented
in 1925 by Oscar T. Bloom.
 The test determines the weight in grams needed by a
specified plunger to depress the surface of the gel by 4
mm without breaking it at a specified temperature.
 The number of grams is called the bloom value, and
most gelatins are between 30 and 300gm bloom.
 The higher a bloom value, the higher the melting and
gelling points of a gel, and the shorter its gelling times.

41. Content uniformity
 Determine the content of the active ingredient in each of 30 capsules (hard or soft) taken
at random.
 10 of which is assayed by the specific procedure. The requirements are met if 9 of the 10
are within the specified potency range of 85 – 115% , and the tenth is not outside 75 –
125% .
 If more than 1 , but less than 3 , of the first 10 capsules fall outside the 85 – 115% limits,
the remaining 20 are assayed .
 The requirements are met if all 30 capsules are within 75 – 125% of the specified potency
range , and not less than 27 of the 30 are within the 85 – 115% range .

42. Reference
 L Lachman, HA Lieberman, JL Kanig. The Theory and Practice of Industrial
Pharmacy, 3rd Edition, Lea & Febiger, Philadelphia, 1986, 374-398.
 Haleem RM, Salem MY, Fatahallah FA, Abdelfattah LE. Quality in the
pharmaceutical industry - A literature review. Available :
http://www.sciencedirect.com/science/article/pii/S1319016413001114.
 Indian Pharmacopoeia Commission. Indian Pharmacopoeia. 7th ed. Ghaziabad:
Indian Pharmacopoeia Commission; 2014.
 United States Pharmacopeial Convention. United States Pharmacopoeia 33-
National Formulary 28. USA: Stationery Office; 2010.
 British Journal of Pharmaceutical Research 9(2): 1-9, 2016, Article no.BJPR.22044
ISSN: 2231-2919.