Polymorphic Transformation of Indomethacin Under High Pressures*

To study the effect of pressure on polymorphic transformation, intact powder, and ethanol slurry of α, γ, and amorphous forms of indomethacin (IMC) were compressed under high pressures. A quantifying method for the percentages of these three constituents in sample powder was established. Using this method, analysis of compressed samples revealed that α form, which is difficult to prepare in stable form under atmospheric pressure, was easily obtained in stable form from the ethanol slurry of the amorphous IMC, which does not include any specific crystalline forms. In the ethanol slurry of γ form, transformation to α form was observed: a reciprocal phenomenon under atmospheric pressure. These results can be rationally explained as follows: α form is more easily crystallized than γ form in the ethanol solution, the more closely-packed crystal structure of α form is thermodynamically predominant over γ form under high pressure, and pressure-induced amorphization occurs. This study indicates that crystallization experiments from the slurry of amorphous samples under various pressures can be useful in screening polymorphic or other solid states. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association.