Stability study of drugs
Stability of pharmaceutical product may be defined as the capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, therapeutic and toxicological specification.
Instability may cause
– Undesired change in performance, i.e. dissolution/bioavailability
– Substantial changes in physical appearance of the dosage form
– Causing product failures
Factors affecting Stability
1- Environmental factors
– Temperature – Light
– Oxygen – Moisture
– Carbon dioxide
2- Drugs or excipients in the dosage form
-Particle size of drug
-pH of the vehicle
3- Microbial contamination
4- Trace metal Contamination
5- Leaching from containers
Stability testing/study is termed as a complex process because of involvement of a variety of factors including
1.stability of the active ingredients
2.container/closure system used for packaging
3.heat and moisture conditions encountered during shipment, storage and handling.
4.type of dosage form
5.interaction between active ingredients and excipients
Need for Stability Study
- Provide evidence as to how the quality of the drug product varies with time.
- Establish shelf life for the drug product.
- Determine recommended storage conditions
- Determine container and closure system suitability.
- Safety point of view of patient.
Types of Stability
- THEARAPEUTICAL STABILITY
- PHYSICAL STABILITY
- TOXICOLOGIC STABILITY
- MICROBIOLOGICAL STABILITY
- CHEMICAL STABILITY
1. Physical degradation
2. Chemical degradation
Microbiological stability implies that:
The formulation has not suffered from any microbiological attack and is meeting the standards with respect to lack of contamination/sterility.
Sources of Microbial Contamination:
|Water||gram-negative groups: Pseudomonas,
|Air||Mould spores: Penicillium, Aspergillus
Bacterial spores: Bacillus spp. Yeasts
|Animal products||Salmonella, Coliforms|
|Personnel||Coliforms, Staphylococci, Sterptococci|
- Preformulation is branch of pharmaceutical science that investigate physico-chemical properties of new drug compounds in order to develop safe, effective, and stable dosage form.
Goals of Preformulation
- To develop the necessary physicochemical parameters of new drug substances.
- Determining the kinetic rate profile.
- To set uo physical characteristics
- Compatibility with common excipients
- Formulating an elegant, safe, efficacious dosage form with good bioavailability.
- To formulate new dosage form of already existing drug.
Some commonly evaluated parameters
- Crystallinity & Polymorphism
- Particle size & shape and
- Bulk density
- Surface area and Solubility