Stressed stability studies

Comparative Stress Stability Studies for Rapid Evaluation of Manufacturing Changes or Materials from Multiple Sources... 

In this chapter, considerations are described for conducting comparative stress stability studies. Examples are presented to illustrate considerations and approaches for using stress conditions to compare sample stability. Finally, a statistical modeling approach is described, whereby the stability of a labile compound is modeled as a function of moisture and temperature. While requiring more time than some stress condition studies, this approach allows prediction of stability behavior over a wide range of conditions and ultimately saves time by eliminating the need for additional studies. 

Considerations involved in planning, conducting, and interpreting comparative stress stability studies are outlined in Table 1 and discussed below. 

Accelerated or stress stability studies for the purpose of predicting sample shelf life at normal conditions have been investigated for many years. In addition, some examples of stress stability studies for sample comparison have been described. Goldberg and Nightingale (25) compared the stability of aspirin in a combined dosage form with propoxyphene. The hydrolysis... 

Is the method specific and stability indicating as shown by analysis of samples subjected to stressed stability studies (pH, light, heat, oxidation) Normally, specificity is determined through peak purity using ultraviolet (UV) diode array or liquid chromatography (LC)/mass spectrometry (MS) analysis. In methods for analysis of drug products, placebo formulations (and stressed placebos) must yield blank chromatographic baselines. The development... 

Additional preformulation and physicochemical characterization of the candidate compound are performed and stress stability studies may be initiated. Ideally, the optimal solid state (polymorphic) and chemical (salt) form of the molecule are identified as part of clinical candidate selection. Selection of the most stable and bioavailable form will expedite subsequent development. The methods for testing the drug substance are refined and additional methods may be developed. 

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