Characterization of the “hygroscopic” properties of active pharmaceutical ingredients

ABSTRACT

The amount of water vapor taken up by an active pharmaceutical ingredient (API) as a function of relative humidity is routinely evaluated to characterize and monitor its "hygroscopicity" throughout the drug development process. In this minireview we address the necessity of going beyond the measurement of water vapor sorption isotherms to establish the various mechanisms by which solids interact with water and the important role played by the crystalline or amorphous form of the solid. Practical approaches for choosing experimental conditions under which water vapor sorption should be measured, including the pre‐treatment of samples and the time allowed to reach an equilibrium state are presented. With the assistance of a flowchart, we provide a basis for the systematic examination of samples to establish the likely mechanisms of sorption and the indicators pointing toward future problems with physical and chemical instabilities. Finally, we present strategies for managing materials that might be susceptible to the detrimental effects of water vapor sorption. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1047–1059, 2008