Stability Studies

Module 6 : Pharmaceutical Preformulation : Basics and Industrial Applications

Types of Stability Studies

Inherent stability of drug substance is a critical component of preformulation studies and provides numerous inputs for development of the drug product. Various stages like processing, storage and gastrointestinal milieu, challenge the stability of a drug substance. A typical preformulation protocol involves studies to assess chemical stability, physical stability and photostability. Chemical stability is performed both in solid state and solution state. It is an established fact that solid state and solution state stability can differ both qualitatively and quantitatively.

Stability Chambers

Experimental Determination of Stability

Extensive studies are performed for chemical stability of the drug substance, by exposing it to variety of stressors. These studies also provide information of the degradation products and help in developing meaningful specifications. Most common pathways for drug degradation include hydrolysis, oxidation and photochemical degradation. Solution thermal degradation studies are performed by exposing solution of drug substance to elevated temperatures and quantifying the remaining drug. The data obtained from these studies can be fitted in mathematical models to calculate reaction kinetics and predict shelf life.

Solid State Studies

tability Solid state degradation studies are more difficult to interpret as they do not follow Arrhenius kinetics outside a narrow range. Simultaneous phase transformations in crystallinity and solvation state, add further complexity to the data interpretation. Usually solid state studies are performed in presence of moisture, to simulate ubiquitous presence of water in pharmaceutical systems. It is also becoming increasingly important to understand effect of unit processes on phase transformation of drug substance, to satisfy regulatory expectations of QbD. Energy intensive unit processes like milling, drying and compaction can trigger solid phase transformations, with consequent impact on stability and performance. Hence it is important to include these studies in the stability assessment.

Stability can change with change in pH

pH stability studies both in solution state and solid state, are performed and help in understanding the fate of drug substance in gastrointestinal milieu. It also indicates the need for controlling the pH of the micro-environment in formulation matrix.

Stability Studies and Formulation Development

Stability studies provide useful inputs for formulation development, processing and packaging development. Need for (i) addition of stabilizing excipients, (ii) environment control during manufacturing and (iii) protective packaging systems, can be proactively identified from the findings of these stability studies.

Dr. Arvind Bansal


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