Quality Control of Capsules

Capsule is a shell or a container prepared from gelatin containing one or more medicinal and/or inert substances. The gelatin capsule shell may be soft or hard depending on their formulation. Capsules are intended to be swallowed whole by the patient.

Capsules are preparations with hard or soft shells, of various shapes and capacities, usually containing a single dose of medicament. Types of capsules: hard, soft, enteric, and modified-release capsules.

Quality Control Tests for Capsules:

I.      Standard for content of active ingredients in capsules:

This test determines the amount of active ingredient by the method in the assay. 

II.      Disintegration:

Disintegration is the state in which no residue except fragments of capsule shell, remains on the screen of the test apparatus or adheres to the lower surface of the disc.  The disintegration test determines wither tablets or capsules disintegrate within a prescribed time when placed in a liquid medium under the prescribed experimental conditions. 

Method:

According to the B.P. and applies to hard and soft capsules.

Introduce one capsule into each tube and suspend the apparatus in a beaker containing 600 ml water at 37^oC. If hard capsules float on the surface of the water, the discs may be added. Operate the apparatus for 30 minutes; remove the assembly from the liquid. The capsules pass the test if

1.      No residue remains on the screen of the apparatus 

2.  If a residue remains, it consists of fragments of shell is a soft mass with no palpable core

4.      If the disc is used, any residue remaining on its lower surface should only consist of fragments of shell.

III.      Uniformity of Weight:

This test applies to all types of capsules and it is to be done on 20 capsules.

Method:

Weigh an intact capsule. Open the capsule without losing any part of the shell and remove the contents as completely as possible. Weigh the shell. The weight of the contents is the difference between the weighing. Repeat the procedure with a further 19 capsules selected at random. Determine the average weight.

Limit:

Not more than two of the individual weights deviate from the average weight by more than the percentage deviation shown in the table below, and none deviates by more than twice that percentage.

Average Wt of Capsule Content	Percentage Deviation
Less than 300 mg	10
300 mg or more	7.5

Observation Table:

Capsule Number	Wt. of intact capsules (A)	Wt. of empty shell (B)	Wt of contents = A - B
up to 20
Total wt			X

Average weight = X / 20

Upper limit = average weight + (Average weight * % error)

Lower limit = average weight - (Average weight * % error)

Pharmacopoeial quality control tests for tablets

British pharmacopoeia

1.       For all tablets:

                                  I.            Content of active ingredients

                                II.            Disintegration

                              III.            Uniformity of content

                              IV.            Labeling. 

2.       Uncoated  tablets:

                                  I.            Disintegration test

                                II.            Uniformity of weight

3.       Effervescent tablet:

                                  I.            Disintegration test

                                II.            Uniformity of weight

4.       Coated tablet:

                                  I.            Disintegration test

                                II.            Uniformity of weight

Indian pharmacopoeia

Uncoated tablet:

1.       Uniformity of container content

2.       Content of active ingredient

3.       Uniformity of weight

4.       Uniformity of content

5.       Disintegration test

Enteric coated tablet:

1. Disintegration test

Dispersible tablet:

1. Uniformity of dispersion
2. Disintegration

Soluble tablet:

1. Disintegration test

Effervescent tablet:

1. Disintegration/ Dissolution / Dispersion test.

United states pharmacopoeia

Physical tests applicable to tablet formulation:

1.       Bulk density / Tapped density of powder

2.       Powder fineness

3.       Loss on drying

4.       Disintegration test

5.       Tablet friability

6.       Dissolution test

7.       Drug release testing

8.       Uniformity of dosage form

9.       Container permeation test

10.   Labeling of inactive ingredients

Evaluation of Tablets

Official and unofficial tests for evaluation of tablets

Official Tests:

1.       Weight variation

2.       Disintegration  

3.       Dissolution

4.       Drug content

Non-Official Tests:

1.       Hardness

2.       friability

General Appearance:

 The general appearance of a tablet, its identity and general elegance is essential for consumer acceptance, for control of lot-to-lot uniformity and tablet-to-tablet uniformity. The control of general appearance involves the measurement of size, shape, color, presence or absence of odor, taste etc.

Size & Shape:

It can be dimensionally described & controlled. The thickness of a tablet is only variables. Tablet thickness can be measured by micrometer or by other device. Tablet thickness should be controlled within a ± 5 % variation of standard value.

Unique identification marking:

These marking utilize some form of embossing, engraving or printing. These markings include company name or symbol, product code, product name etc. 

Organoleptic properties & hardness of tablets

Color distribution must be uniform with no mottling. For visual color comparison compare the color of sample against standard color.

Hardness :

Tablet requires a certain amount of strength or hardness and resistance to friability to withstand mechanical shocks of handling in manufacture, packaging and shipping. Hardness generally measures the tablet crushing strength.

Hardness (crushing strength):

It is the load required to crush the tablet when placed on its edge.To determine the need for pressure adjustments on the tableting machine.  Hardness can affect the disintegration. So if the tablet is too hard, it may not disintegrate in the required period of time.  And if the tablet is too soft, it will not withstand the handling during subsequent processing such as coating or packaging.  In general, if the tablet hardness is too high, we first check its disintegration before rejecting the batch.  If the disintegration is within limit, we accept the batch. If Hardness is high + disintegration is within a time accept the batch.

Pfizer type hardness tester

                                     Monsento type hardness tester

Factors Affecting the Hardness:

a)     Compression of the tablet and compressive force.

b)     Amount of binder. (More binder à more hardness)

c)      Method of granulation in preparing the tablet (wet method gives more hardness than direct method, Slugging method gives the best hardness).

Limits: 5 kilograms minimum and 8 kilograms maximum.

 Make hardness test on 5 tablets and then take the average hardness.

Friability:

Friability of a tablet can determine in laboratory by Roche friabilator. This consist of a plastic chamber that revolves at 25 rpm, dropping the tablets through a Distance of six inches in the friabilator, which is then operate for 100 revolutions. The tablets are reweighed. Compress tablet that lose less than 0.5 to 1.0 % of the Tablet weigh are consider acceptable.

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 Rouch friabilator is used to evaluate the ability of the tablet to withstand abrasion in packaging, handling, and shipping.

Procedure:

1. Weigh 20 tablets together = 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 (only the intact ones) = W2

Friability (% loss) = W1 - W2/100

 It must be less than or equal to1 % but if more we do not reject the tablets as this test is non-official .Perform this test using 20 tablets that were used first in the weight variation test.

Thickness test

Thickness is an unofficial test. Thickness of the tablet is inversely proportional to hardness i.e. increase in hardness decrease the  thickness & vice versa. Thickness of tablet is measured by Vernier caliper/screw gauge. It is determined for 10 tablets.

Weight variation test (uniformity of weight)

   Weigh 20 tablet selected at random, each one individually . X1, X2, X3… Xz

Determine the average weight. X= (X1+X2 +X3+…+ Xz)/20

Limit:

Upper limit = average weight + (average weight  % error)

Lower limit = average weight - (average weight  % error)

The individual weights are compared with the upper and lower limits.

Not more than two of the tablets differ from the average weight by more than the % error listed, and no tablet differs by more than double that percentage.

Weight variation tolerances for uncoated tablets

USP -NF standards

SN	Average wt. of tablet(mg)	Max. % difference allowed
1	130 or Less	10%
2	130-324	7.5%
3	More than 324	5%

Indian Pharmacoepia Standards

SN	Average wt. of tablet(mg)	Max. % difference allowed
1	84  or Less	10%
2	84-  250	7.5%
3	More than 250	5%

Content Uniformity Test:

It is an official test. Randomly select 30 tablets. 10 of these assayed individually. The Tablet pass the test if 9 of the 10 tablets must contain not less than 85% and not more than 115% of the labeled drug content and the 10th tablet may not contain less than 75% and more than125 % of the labeled content. If these conditions are not met, remaining 20 tablets assayed individually and none may fall outside of the 85 to 115 % range.