Presentatio on IPQC for Capsules by Akshay Trivedi 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".[1] This approach places an emphasis on three aspects (enshrined in standards such as ISO 9001)[2][3]: Elements such as controls, job management, defined and well managed processes,[4][5] performance and integrity criteria, and identification of records Competence, such as knowledge, skills, experience, and qualifications Soft elements, such as personnel, integrity, confidence, organizational culture, motivation, team spirit, and quality relationships. Inspection is a major component of quality control, where physical product is examined visually (or the end results of a service are analyzed). Product inspectors will be provided with lists and descriptions of unacceptable product defects such as cracks or surface blemishes for example.[3] The quality of the outputs is at risk if any of these three aspec Modern humans are distinguished from other species by their extensive use of tools to control and adapt to their surroundings. Early stone tools such as anvils had no holes and were not designed as interchangeable parts. Mass production established processes for the creation of parts and system with identical dimensions and design, but these processes are not uniform and hence some customers were unsatisfied with the result. Quality control separates the act of testing products to uncover defects from the decision to allow or deny product release, which may be determined by fiscal constraints.[6] For contract work, particularly work awarded by government agencies, quality control issues are among the top reasons for not renewing a contract.[7] The simplest form of quality control was a sketch of the desired item. If the sketch did not match the item, it was rejected, in a simple Go/no go procedure. However, manufacturers soon found it was difficult and costly to make parts be exactly like their depiction; hence around 1840 tolerance limits were introduced, wherein a design would function if its parts were measured to be within the limits. Quality was thus precisely defined using devices such as plug gauges and ring gauges. However, this did not address the problem of defective items; recycling or disposing of the waste adds to the cost of production, as does trying to reduce the defect rate. Various methods have been proposed to prioritize quality control issues and determine whether to leave them unaddressed or use quality assurance techniques to improve and stabilize production.[6] Notable approaches

1. IPQC FOR CAPSULE
• PREPARED BY : AKSHAY TRIVEDI
• ENROLLMENT NO. : 201804103910007
• M.PHARM – PQA (1ST SEM)
• MALIBA PHARMACY COLLEGE
• UKA TARSADIYA UNIVERSITY
1

2. WHAT IS IPQC?
IPQC is the activity performed between QC and QA.
It is a planned system to identify the materials,
equipments, processes, and operators; to enforce
the flow of manufacturing and packaging
operations according to the established rules and
particles; to minimize human error to detect the
error if and when it does occur; and to pinpoint the
responsibility to the personnel involved in each
unit operation of the entire process.
2

3. In general, in process control procedures are
usually rapid and simple tests or inspection that are
performed when the manufacturing of the product
batch in process.
During manufacturing process in process materials
should be tested for identity, strength, quality and
purity as appropriate and approved or rejected by
the QC unit during the production process.
3

4. The function of IPQC involves monitoring and if
necessary adaption of the manufacturing process
with a view to comply with pharmacopoeias.
4

5. IPQC TESTS FOR CAPSULES
1. BULK DENSITY AND TAPPED DENSITY
2. POWDER COMPRESSIBILITY
3. ANGLE OF REPOSE
4. PARTICLE SIZE DISTRIBUTION
5. APPEARANCE
6. GEL STRENGTH OF GELATIN
7. VISCOSCITY
8. DIMENSIONS OF HARD GELATIN CAPSULE SHELLS
9. UNIFORMITY OF WEIGHT
10. UNIFORMITY OF CONTENT
11. CONTENT OF ACTIVE INGREDIENTS
12. DISINTEGRATION TEST
13. DISSOLUTION TEST
5

6. BULK DENSITY
the ratio of the mass to the volume
Bulk density is determined by measuring the
volume of a known mass Of powder sample that
has been passed through screen into a graduated
cylinder (Method l) through a volume-measuring
apparatus into a cup (Method II).
6

7. Method I-Measurement in a Graduated'-
cylinder
Procedure-
unless otherwise specified pass a quantity of material
sufficient to complete the test through a 1.00 mm(NO.18)
screen to break up agglomerates that may have formed
during storage into a dry 250 ml cylinder introduce ,without
compacting, approximately 100g of test sample, M weighed
with 0.1% accuracy.
Select a sample mass having an untapped apparent volume
of 150-250ml
A 100 ml cylinder is used for apparent volume between 50
mL and 100mL.
7

8. Carefully level the powder without compacting ,if
necessary and read the unsettled apparent volume
V0 to the nearest graduated unit .
Calculate the bulk density in g per mL by this
formula
Bulk density = Mass of granules
Bulk volume of granules
8

9. TAPPED DENSITY
Tapped density is achieved by mechanically tapping
a measuring cylinder containing a' powder sample.
after observing the initial volume, the cylinder is
mechanically tapped, and volume readings are
taken until little further volume change is observed.
The mechanical tapping is achieved by raising the
cylinder and allowing it to drop under its own
weight a specified distance by either of two
methods as described below.
9

10. METHOD I
Procedure :-
Unless otherwise specified, pass a quantity of
material sufficient to complete the test through a
1.00-mm (No. 18) screen to break up agglomerates
that may have formed during storage Into a dry
250-mL glass graduated cylinder (readable to 2 mL)
weighing 220±44 g and mounted on a holder
weighing 450±10 g introduce, without compacting,
approximately 100 g of test sample (M) weighed
with 0.1% accuracy.
10

11. If it is not possible to use 100 g, the amount of the
test sample may be reduced and the volume of the
cylinder may be modified by using a suitable 100-
mL graduated cylinder (readable to 1 mL) weighing
130± 16 g and mounted on a holder weighing
240±12 g.
The modified test conditions are specified with the
results. Carefully level the powder without
compacting, if necessary , and read the ,unsettled
apparent volume(Vo) ,to the nearest graduated
unit.
11

12. Mechanically tap the cylinder containing the sample by
raising the cylinder and allowing it to drop under its own
weight using a suitable mechanical tapped density ,tester
,that provides a fixed drop of 14 ± 2 mm at a nominal rate of
300 drops per minute.
Unless otherwise specified, tap the cylinder 500 times
initially and measure the tapped, volume (V0), to the
nearest graduated unit. Repeat the, tapping
an additional 750 times and measure the tapped volume
(V0) to the nearest graduated unit.
12

13. If the differences between the two volumes is
less, than 2%, (V0) is the final tapped volume, (Vf )
Repeat in increments of 1250 taps as needed; until
the difference between succeeding measurements
is 'less than 2%.
Calculate the tapped density, in g per mL., by this formula-
= M
Vf
13

14. METHOD 2
as directed under Method 1 except that ,suitable
mechanical tapped density tester that provides a
fixed drop of 3 mm (±10%) at a nominal rate Of
250 drops per minute is used: '.
14

15. POWDER COMPRESSIBILITY
The Compressibility Index. and Hausner’s Ratio are
measures of the propensity of a powder to be compressed.
As such, they are measures of the relative importance of
inter particulate interactions.
In a free-flowing powder, such interactions are generally
less significant, and the bulk and tapped densities will be
closer in value.
For poor flowing materials, there are frequently, greater
interparticle interactions, and a greater difference between
the bulk and tapped densities will be observed. These
differences are reflected in the Compressibility Index and
the Hausner’s Ratio.
15

16. Compressibility Index-Calculate by the formula
=100×(Vo – Vf)
Vo
Hausner’s Ratio-Calculate by the formula
= Vo
VF
16

17. U.S. PHARMACOPOEIA 2009 , VOLUME-1 ,P-689-690. 17

18. ANGLE OF REPOSE
Definition: It is defined as maximum angle possible
between the surface of a pile of the powder and the
horizontal plane.
Method :Form the angle of repose on a fixed base. Vary
the height of the funnel to carefully build up a
symmetrical cone of powder.
The funnel height should be maintained approximately
2-4 cm from the top of the powder pile as it is being
formed in order to minimize the impact of falling
powder on the tip of the cone.
18

19. Determine the angle of repose by measuring the
height of the cone of powder and calculating the
angle of repose, from the following equation:-
ϴ= tan-1(h/r)
where, ϴ = angle of repose.
h = height of pile.
r = radius of base.
19

20. U.S. PHARMACOPOEIA 2009 , VOLUME-1 ,P-689-690. 20

21. PARTICLE SIZE DISTRIBUTION
Sieving is one of the oldest methods of classifying
powders and granules by particle size distribution
SIEVING METHODS
LIGHT OBSCURATION PARTICLE COUNT TEST
MICROSCOPIC PARTICLE COUNT TEST
21

22. If the test specimen weight is not given in the
monograph for a particular material, use a test
specimen having, weight between 25 and 100 g,
depending on the bulk density of the material.
22

23. 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, swelling, printing mistake or
discoloration of the shell. Defective capsules should
be rejected .
23

24. GEL STRENGTH OF GELATIN
Pipet 105 mL of water at,100 to 15° into a standard Bloom
bottle, add 7.5 g of Gelatin, and stir Allow to stand for 1
hour, then bring to a temperature of 62° in 15 minutes by
placing in a water bath regulated at 65° (the substance may
be swirled several times to aid solution).
Finally mix by inversion, allow to stand for 15 minutes, and
place in a water bath at 10±0.10. Chill, without disturbance,
for 17 hours Determine the gel strength in a Bloom
Gelometer (a device-developed to make this determination
under standardized conditions) .
24

25. VISCOSCITY
Viscosity is a property of liquids that is closely related to the resistance
to flow.
basic unit is the “poise”
Measurement of Viscosity - The usual method for measurement of
viscosity involves the determination of the time required for a given
volume of liquid to flow through a capillary.
Ostwald-Type Viscometer,
Brookfield viscometer,
Rotouisco meter,
Stormer viscometer.
25

26. DIMENTIONS OF HARD GELATINE
CAPSULE SHELLS
Hard Gelatine Capsule Shells normally used for the
incorporation of medicaments are cylindrical in
shape but other shapes are also formed for special
requirements. The shells of the capsules consists of
two prefabricated cylindrical sections, one end of
which is rounded and the other is open
26

27. 27

28. UNIFORMITY OF WEIGHT
Weigh individually 20 units selected at random or,
for single dose preparations in individual
containers, the contents of 20 units, and calculate
the average weight. Not more than two of the
individual weights deviate from the average weight
by more than the percentage shown in the table
and none deviates by more than twice that
percentage.
28

29. Weigh an intact capsule.
Open it without losing any part of the shell and
remove the contents as completely as possible.
For soft gelatine capsules, wash the shell with a
suitable solvent and keep aside until the odour of
the solvent is not perceptible.
Weigh the shell The difference between the
weighing gives the weight of the contents. Repeat
the procedure with another 19 capsules.
29

30. Hard capsules containing 25 mg or more of a drug
substance contain 25% or more, by weight, of the
dosage unit Of in the case of hard capsules, the
capsule contents, except-that uniformity of other
drug substances present in lesser proportions is
demonstrated by meeting Content Uniformity
Requirements.
30

31. UNIFORMITY OF CONTENT
It is pharmaceutical analysis parameter for the
quality control of capsules. Multiple capsules are
selected at random and a suitable analytical
method is applied to assay the individual content
of the active ingredient in each capsule.
The preparation complies if not more than one
individual content is outside the limits of 85 to
115% of the average content and none is outside
the limits of 75 to 125% of the average content.
INDIAN PHARMACOPOEIA 2010 , VOLUME-1 ,P-192
31

32. The preparation fails to comply with the test if more than
3 individual contents are outside the limits of 85 to 115%
of the average content or if one or more individual
contents are outside the limits of 75 to 125% of the
average content.
Calculation of Acceptance Value Calculate the acceptance
value by the formula: .
|M-X|+ks
32

33. CONTENT OF ACTIVE
INGREDIENT
For this test determine the amount of active ingredient
by the method described in the assay and calculate the
amount of active ingredient per capsule .
The capsule complies with the test if content of active
ingredient lies within the stated range The range is
based on the requirement that 20 capsule, or such
other number indicated in the monograph Where 20
capsule are not available a smaller number not less
than 5 can be used, for this smaller number tolerances
are widened in accordance with given capsule.
33

34. DISINTEGRATION TEST
For the purpose of this test, disintegration does not
imply complete solution of the dosage unit or even
of its active constituent.
Disintegration is defined as that state in which no
residue of the unit under test remains on the
screen of the apparatus or, if a residue remains, it
consists of fragments of disintegrated parts of
capsule shells.
34

35. Method-Unless otherwise stated in the individual monograph,
introduce one tablet or capsule into each tube and, if directed in
the appropriate general monograph, add a disc to each tube.
Suspend the assembly in the beaker containing the specified
liquid and operate the apparatus for the specified time. Remove
the assembly from the liquid. The tablets or capsules pass the
test if all of them have disintegrated.
If 1 or 2 capsules fail to disintegrate, repeat the test on 12
additional capsules; If the capsules adhere to the disc and the
preparation under examination fails to comply, repeat the test
omitting the disc. The preparation complies with the test if all the
capsules in the repeat test disintegrate.
35

36. DISSOLUTION TEST
1. Conventional-release dosage forms
2. Prolonged-release dosage forms
3. Modified-release dosage forms
36

37. Conventional-release dosage
forms
37

38. Prolonged-release dosage
forms
38

39. Modified-release dosage
forms
39

40. REFERENACE :-
United States Pharmacopeia Convention. Unite
States Pharmacopoeia 33-National Formulary 28.
USA: Stationery Office; 2010.
Indian Pharmacopoeia Commission. Indian
Pharmacopoeia. 7th ed. Ghaziabad: Indian
Pharmacopoeia Commission; 2010.
40

41. 41
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