Quality Assurance procedures for Tablets

DINESH KUMAR Mankaran Singh Deepak Sharma Gurmeet Singh M.PHARMACY PHARMACEUTICS CT Institute of Pharmaceutical sciences Jalandhar, INDIA AICTE , PCI approved

Quality
In manufacturing, a measure of excellence or a state of being free from defects, deficiencies, and significant variations, brought about by the strict and consistent adherence to measurable and verifiable standards to achieve uniformity of output that satisfies specific customer or user requirements. Quality, simplistically, means that a product should meet its specification.

Quality Assurance
It is the sum total of the organized arrangements with the objective of ensuring that products will be of the quality required for their intended use.

Quality of Tablet could be effected by

Unit variable Unit step Unit process

which could be explained by FISH-BONE DIAGRAM

A simple FISHBONE diagram of the Processing steps and in Process variables during Tablet manufacturing that may influence the quality and consistency of final product dose uniformity
PREBLENDING (1-3)
SPEED LOAD TIME TIME

DRYING (9-11)
TEMP. SIZE

BLENDING (15-17)
SPEED LOAD TIME

D O S E

TIME SPEED LOAD RATE SPEED SCREEN

RATE SPEED FORCE

AMOUNT

SIZING (12-14)

TABLETING (18-19)

GRANULATING (4-8)

U N I F O R M I T Y

Processing Problems associated with Tablets

Capping and Lamination Picking and Sticking Mottling Poor flow Poor mixing Double impression

Quality of tablets should fulfill certain specifications

1. The tablet should include the correct dose of the drug. (Weight uniformity and content uniformity test) 2. The drug should be released from the tablet in a controlled and reproducible way . (Dissolution test) 3. The tablet should show sufficient mechanical strength to withstand fracture and erosion during manufacturing and handling. (Hardness and friability test) 4. The appearance of the tablet should be elegant and its weight, size and appearance should be consistent .(Visual observation, weight variation, thickness and diameter of the tablet) 5. The tablet should be packed in a safe manner.

Quality control tests and specifications for some of these properties are given in pharmacopoeias. The most important for these are;
Weight uniformity Dose uniformity The drug release in terms of tablet disintegration and drug dissolution Resistance of tablets to fracture in terms of friability and harness testing The microbial quality of the product

These factors must be controlled during production (in-process control) and verified after production. Some test methods are described in the pharmacopeias; others are not and thus are referred to as "non-compendial" tests.

A part of Good Manufacturing Practice (GMP), the production run is monitored under control chart. At regular intervals (10-15 min.) during the course of manufacturing, the operator must sample specified number of tablets for testing (in-process control) e.g. weight of tablet, tablet thickness, friability, disintegration time,

Official Quality control tests for tablets (Compendial tests)

British Pharmacopoeia (B.P.) & US Pharmacopoeia (USP) 1- Uniformity of content of active ingredient (Uniformity of weight & Content uniformity) 2- Disintegration test. 3- Dissolution test. 4- Friability test.

USP mentions some Q.C. tests before the powder is compressed e.g. powder fineness, density,

I- Compandial tests
1- Uniformity of active ingredient
Traditionally, dose variation between tablets is tested in two separate tests; 1- Weight uniformity 2- Content uniformity If the drug forms greater part of the tablet, any variation in the tablet weight obviously indicates a variation in the active ingredient. (Weight uniformity test) If the drug is potent (USP specifies 50 mg of the active ingredient or less), the excipients form the greater part of the tablet weight and the correlation between the tablet weight and amount of the active ingredient can be poor, in this case another test (Content uniformity) must be performed.

A. Weight uniformity (B.P. design)

Weigh 20 tablets individually (i.e. determine the weight of each tablet alone; X1, X2, X3 X20)
Calculate the average weight of tablets ( = Total weight of tablets ) Number of tablets Average weight of tablets (X) = (X1+X2 +X3++ X20)/20

B. Content uniformity
USP defines content uniformity test for tablets containing 50 mg or less of drug substance in case of uncoated tablets and for all sugar coated tablets regardless to the drug content.

USP design: Ten tablets are individually assayed for their content (according to the method described in the individual monograph) The requirements for content uniformity are met if the amount of the active ingredient in each tablet lies within the range of 85-115 % of the label claim.

Non-Compandial tests
There are many tests are frequently applied to tablets for which there are non-pharmacopoeial requirements but will form a part of manufacture's owner product specifications.

1- Tablet thickness 2- Tablet hardness

II- Non-Compandial tests

1. Tablet thickness
Tablet thickness is important for tablet packaging; very thick tablets affect packaging either in blisters or plastic containers. The tablet thickness is determined by the diameter of the die, the amount of fill permitted to enter the die and the force or pressure applied during compression. The thickness of the tablet may be measured manually or by automatic equipment.

2. Hardness test
In general, tablets should be sufficiently hard to resist breaking during normal handling, packaging and shipping, and yet soft enough to disintegrate properly after swallowing.

Hardness of the tablet is controlled by (or is affected by) the degree of the pressure applied during the compression stage.
Hardness is an important criterion, since it can affect disintegration and dissolution.

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