The phase (trans)formation and physical state of a model drug in mesoscopic confinement

Compounds embedded into mesoporous or even microporous matrices are interesting for many emerging applications, such as novel catalysts, sensors, batteries, hydrogen storage materials or modern drug delivery devices. We report on two unexpected phenomena regarding the structural and dynamic properties of a model drug substance (indomethacin) when confined in mesoscopic matrices. Firstly, we show that the confinement directs the crystallization of the drug into a stable polymorph that is not otherwise formed at all; its relative amount depends on the pore size. This phenomenon is also explained theoretically using a modified classical heterogeneous nucleation theory. Secondly, we demonstrate that--even at relatively low volume fractions--the confined drug forms a condensed phase in a way that obstructs the passage of the pore channels. This may have far-reaching consequences for understanding the mechanisms of drug release from porous matrices.