Quality Control Requirements for Pharmaceutical Dosage Forms

Quality control of pharmaceutical formulations is an essential operation in the production of drugs. It is a procedure or set of procedures designed to ensure the output of uniform batches of drugs conforms to the established specifications. This requires organization and strict quality checks at each level of production.

Quality control is concerned with both quality and quantity. The quality of pharmaceutical dosages forms must be built in during plant construction, product research and development, purchasing of materials, production, testing, inspection, packaging, labelling, storage, and distribution.  It cannot be assumed that finished product testing alone will ensure product quality.

This article provides an overview of quality control requirements for dosage forms and the types of tests needed for their evaluation.

Good Manufacturing Practice

Good Manufacturing Practice (GMP) is a requirement that drugs and methods used in or the facilities or controls used in their manufacture, processing, handling or packaging conform 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.

Quality Assurance (QA)

Quality assurance is the totality of arrangements made with aim of ensuring that pharmaceutical products are of the quality required for their intended use. This includes all that influences the quality of the product.

QA = QC + GMP

Quarantine

The status of starting or packaging materials, intermediates, or bulk or finished products isolated physically or by other effective means while a decision is awaited on their release, rejection or reprocessing.

Common sources of quality variation

When the quality of any drug is given by an industry, then it is responsible for any variation from the standard. Variation in quality may occur due to any mistake during the whole process, that is 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 are:

Materials

1. Variation among suppliers of the same substance.
2. Variation among batches from the same suppliers.
3. Variation within a batch.

Machines

1. Variation of the equipment of the same process
2. Difference in adjustment
3. Ageing machines and improper care

Men

1. Improper working conditions
2. Inadequate training and understanding
3. Lack of interest and emotional upheaval
4. Dishonesty, fatigue and carelessness

Methods

1. Wrong procedure
2. Inadequate procedure
3. Negligence in procedure by chance.

Milieu (Environment or Premises)

This is the fifth source of quality variation. The environment must be clean, dust- free, spacious and properly designed to minimize the risk of errors and permit effective cleaning and maintenance in order to avoid cross-contamination. It must be suitable for the purpose for which it is to be used.

Quality control requirements for oral solid dosage forms (Tablets, Capsules Powders)

1. Evaluation for visual appearance, labelling, odour, taste, texture, hardness and friability.
2. Moisture content: Limits are given in official compendia.
3. Standards and tests of identity: designed to demonstrate clearly that the specimens examined contain the active ingredient(s) they purport to contain.
4. Standards and tests of homogeneity: Apply test for uniformity of weight.
5. Standards and test for purity: for potentially harmful degradation compounds that may be generated during production and storage of dosage forms and for contaminants whose presence may indicate deviation from GMP.
6. Standards and assays for the active ingredient(s) and for degradation products: It provides quantitatively permitted range per tablet or capsule of average weight.
7. Uniformity of content: It involves individual analysis of for a given number of dosage forms to assess possible variation. This test is particularly more important where the declared quantity of active ingredient in a single tablet is less than 5 mg and in case of sugar-coated tablets 10 mg or less.
8. Standards and tests of performance: Designed to provide some assurance that the dosage form will release its active ingredient as intended. Dissolution rate tests for poorly soluble drugs, potent drugs and cases with dissolution problems; disintegration test to supplement dissolution rate tests.
9. Stability indicating tests: This is to take into account the deterioration in activity or strength of the drug product that may occur because of degradation of the active ingredient in the dosage form as well as aspects of physical instability of the product e.g. development of undue colour or colour instability.
10. Storage conditions.

Sterility and apyrogenicity tests are essential additional tests for powdered materials for injection.

Quality Control requirements for semi-solid dosage forms (Ointments, Creams, Jellies and Suppositories)

Tests include:

1. Evaluation for visual appearance, colour, odour, labelling, and homogeneity
2. Loss of water
3. Consistency
4. Softening range (for suppositories)
5. Viscosity
6. Particle size distribution
7. Ph
8. Assay of active ingredients and of degradation products
9. Identification test for active ingredient and possible contaminants
10. Stability of the active ingredient in the dosage form
11. Release of the active ingredient from the dosage form and
12. Storage conditions.

Quality control requirements for liquid preparations

Tests include:

1. Evaluation for visual appearance, colour, taste, odour, labelling, and homogeneity,
2. Assay of active ingredients and of degradation products.
3. Pourability
4. Viscosity
5. Isotonicity
6. Particle size agglomeration and particle size distribution
7. Clarity
8. Crystallization and precipitation
9. Gas evolution
10. Relative density
11. pH
12. Surface tension
13. Microbial limit tests
14. Stability of the active ingredient(s), and identification tests
15. Light stability
16. Container and closure compatibility
17. Redispersibility
18. Suspensibility
19. Storage condition

For liquid products to be used as injections, eye drops or vaccines sterility, apyrogenicity test and particulate matter testing are necessary as additional tests.

Conclusion

The quality of pharmaceutical dosage forms is essential to minimize or eliminate the risk of marketing unsafe products. In order to guarantee quality and consistency of drugs batch to batch, all operations involved in the manufacture of dosage forms, 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

• Samir A. Hanna (1989) Quality Assurance. Drug Development and Industrial Pharmacy, 15:6-7, 869-894, DOI: 10.3109/03639048909043654 
• World Health Organization (2007). Quality assurance of pharmaceuticals: A compendium of guidelines and related materials Volume 2, 2nd updated edition. Switzerland: WHO Press.