Quality Control of Pharmaceutical Tablets

Abstract

Quality control in pharmaceutical industries can be defined as a procedure or set of procedures designed to ensure the output of uniform batches of drugs to the established specifications of pharmaceutical formulations. It is an essential operation in the production of drugs. Quality control essentially requires organization and strict quality checks at each level of production in an industry.This article is aimed at  providing a short review of steps and tests of quality control for pharmaceutical tablets.

Introduction

Tablets are solid drug delivery systems prepared by compressing a single dose of one or more active drug substance(s) with some additives/ pharmaceutical excipients. They may be circular, oblong, oval, triangular or cylindrical in shape and flat-, round-, concave- or convex-faced with straight or bevelled edges.
Quality control of pharmaceutical tablets is concerned with both quality and quantity of the tablets. The quality  must be built in during plant construction, product research and development, purchasing of materials, production, testing, inspection, packaging,labelling, storage, and distribution. And thus cannot be assumed that finished product testing alone will ensure product quality.

Quality Control Practices in Manufacturing of Pharmaceutical Tablets

This includes practices that must be carried out in the process of quality control of pharmaceutical tablets. They are;

1. Quality Assurance (QA)

Quality assurance is all arrangements made with the aim of ensuring that pharmaceutical tablets shows the same level of quality required for their intended use. This includes all that influences the quality of the tablets.

2. Good manufacturing practice(GMP) 

This is a basic requirement that ensures that drugs and methods of production used in the facilities or controls used in the manufacture, processing, handling or packaging of the tablets conforms with those practices that will assure that such drugs meet the quality standards appropriate to their intended use and as required by the marketing authorization.These regulations concern themselves with specific criteria for buildings, equipment, personnel, components, master formula and batch production records, production and control procedures, product containers, packaging and labelling, laboratory controls, distribution records, stability and complaint files.

Factors that affects Quality of Pharmaceutical Tablets  

Variations in quality of pharmaceutical tablets produced may occur due to any mistake during the whole process (from the reception of the raw materials up to the finished product in packed form). Risk of error increases as the materials increases and the method becomes more complicated. Sources of product quality variation during manufacture may include:

1. Manufacturing Materials which can include variations among suppliers of the same substance, among batches from the same suppliers or within a batch.
2. Variations of the equipment of the same process, difference in adjustment, ageing machines and improper care.
3. Improper working conditions, inadequate training and understanding and lack of interest and emotional upheaval. 
4. Wrong procedure, inadequate procedure and negligence in procedure by chance. 
5. The environment may lose a problem in production thereby causing variations due to lack of space, dust or dirty workplace which can cause cross contamination.

Quality Control Tests for Pharmaceutical Tablets

In pharmaceutical tablet formulation, a number of quality control tests are performed to ensure that tablets produced meet the requirements as specified in official compendium and conventional requirements established by the industries over the years. These tests can be grouped into two broad categories namely:

1. Official tests
2. Non-official tests. 

Official or Pharmacopeia Tests. 

These tests are called official tests because the test methods are described in official compendia such as the British Pharmacopoeia, American Pharmacopoeias etc. They are standardized test procedures which clearly state the limits under which compressed tablets could be accepted. These tests include: 

1. Content of Active Ingredient

This is determined by weighing the tablets then they are crushed in a mortar with a pestle. An amount equivalent to the theoretical content of each tablet or the average of the crushed tablets is weighed out in an analytical balance. The weighed powder is dispersed in a solvent in which the active drug is freely soluble or in a solvent prescribed in the individual drug monograph. This is then filtered and an aliquot of the resultant filtrate is subjected to the stipulated assay procedures. Analysis of the active drug is usually carried out using spectrophotometry or High-Performance Liquid Chromatography (HPLC). This results show the content of the active ingredient and verifies it with the .B.P. 

2. Uniformity of Weight/ Weight variation test

The test for uniformity of weight is performed by weighing individually 20 tablets randomly selected from a tablet batch and determining their individual weights. The individual weights are compared with the average weight.

3. Uniformity of Content

This test ensures the content consistency of active drug substances within a narrow range. This test is crucial for tablets having a drug content of less than 2 mg or when the active ingredient comprises less than 2% of the total tablet weight. Here, some tablets are randomly selected, these tablets are assayed individually. The requirements for content uniformity are met if the amount of active ingredient 90% of selected tablets lies within the range of 85% to 115% of the label claim. There are various factors which are responsible for the variable content uniformity in tablets. This may include: Tablet weight variation, uneven distribution of the drug in the powder or granules, segregation of the powder mixture or granulation during formulation processes

4. Disintegration Time Test

This is the time it takes for a tablet to  breakdown into granules or primary powder particles. All USP tablets must pass a test for disintegration, which is conducted in vitro using a disintegration test apparatus.The apparatus consists of a basket-rack assembly containing six open-ended transparent tubes of USP-specified dimensions, held vertically upon a 10-mesh stainless steel wire screen. During testing, a tablet is placed in each of the six tubes of the basket, and through the use of a mechanical device, the basket is raised and lowered in a bath of fluid (e.g. water, or as prescribed in the individual drug monograph) at 29 to 32 cycles per minute, the wire screen always below the level of the fluid. For most normal release tablets, the time permitted is 15 minutes.Tablets are said to have disintegrated if no fragments (other than fragments of coating) remains on the screen, or if particles remain, they are soft without an un-wetted core. Chewable tablets are not required to comply with the test. Disintegration is used as a guide in the preparation of an optimum tablet formula and as an in-process control test to ensure batch to batch uniformity. There are some factors which affect the disintegration of tablets and they include: Medium used, temperature of the test media, operator’s experience, nature of the drug, the diluent used in the formulation, the type and concentration binder used, type and amount of disintegrant used including method of incorporation, the presence of excessive lubricants and overly mixed lubricants, compressional force used.

5. Dissolution Test

This test measures the amount of time required for a given percentage of the drug substance in a tablet to go into solution under a specified set of conditions. It is intended to provide a step toward the evaluation of the physiological availability of the drug substances.
There are various factors which  can affect the dissolution of a drug and they include: Physiochemical properties of the drug, polymorphic form, particle size, salt form, hydrates and anhydrates.In vitro dissolution test is performed using a variety of equipment/apparatus. The British Pharmacopoeia recommends three types of apparatus – the rotating basket, the rotating paddle and the flow-through cell. The static-basket magnetic stirrer assembly can also be used for this test.

Non-Pharmacopoeial or Non-Official Tests

These are tests that are performed on pharmaceutical tablets which are not listed in official compendia and concern a variety of qualities such as the porosity of tablets, hardness or crushing strength test, friability test, tensile strength determination, thickness test etc.

1. Tablet Hardness or Crushing Strength Test

This measures the degree of force in kilograms, pounds, or in arbitrary units needed to fracture a tablet. Besides the concentration of binders used and the compression force, the hardness of a tablet depends on: the characteristics of the granules to be compressed e.g., hardness and deformation under load, the type and concentration of lubricant used and the space between the upper and lower punches at the time of compression.
The crushing strength of tablets is usually checked using Monsanto or Stokes hardness tester, Strong-Cobb hardness tester and the Pfizer crushing strength tester.A force of about 4 kg is considered the minimum requirement for a satisfactory tablet. 

2. Friability Test

This measures the resistance of tablets or granules to abrasion or fracture. The idea behind this test is to mimic the kind of forces, caused by phenomena such as collisions and sliding of tablets towards each other, which a tablet is subjected to during coating, packaging, handling, and shipping.The test is rejected if any tablet caps, laminates or breaks up in course of the test. As a rule of thumb, a maximum weight loss of not more than 1% generally is considered acceptable for most pharmaceutical products. Values of up to 2% or above have been reported in direct compression formulations. The friability of tablets may be influenced by moisture content. A number of instruments are available for friability tests but the most popular and most reliable is the Roche Friabilator.

3. Tablet Thickness

Tablet thickness is determined by the diameter of the die, the amount of fill permitted to enter the die cavity, the compaction characteristics of the fill material, and the force or pressure applied during compression. To manufacture tablets of uniform thickness during and between batch productions for the same formulation, care must be exercised to employ the same factors of fill, die, and pressure. The degree of pressure affects not only thickness but also hardness of the tablet. Thus, for tablets of uniform thickness and hardness, it is doubly important to control pressure. Tablet thickness also becomes an important characteristic in packing operations and in counting of tablets using filling equipment which uses the uniform thickness of the tablets as a counting mechanism.Tablet thickness is measured with a vernier caliper, thickness gauge or automated equipment (Automatic weight, hardness, thickness, and tablet diameter test instrument). The thickness of a tablet should be controlled within ±5% variation of a standard value depending on the size of the tablet.
Other non-pharmacopoeial tests include measurement of tablet diameter, porosity, liquid penetration, mechanical strength, and density, visual appearance, labelling, odour, taste, texture.
CONCLUSION
Assessment of the quality of pharmaceutical tablets is essential to minimize or eliminate the risk of marketing unsafe or substandard products. In order to guarantee quality and consistency of drugs batch to batch, all operations involved in the manufacture of these tablets from receipt of raw materials, through processing, packaging and repackaging, labelling and re-labelling, completion of the finished products, to distribution should be controlled.

References

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