title: The phase (trans)formation and physical state of a model drug in mesoscopic confinement.
abstract: 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.
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, SI-1000 Ljubljana, Slovenia.
authors.forename: Tina
authors.initials: T
authors.lastname: Ukmar
authors.forename: Aljaž
authors.initials: A
authors.lastname: Godec
authors.forename: Odon
authors.initials: O
authors.lastname: Planinšek
authors.forename: Venčeslav
authors.initials: V
authors.lastname: Kaučič
authors.forename: Gregor
authors.initials: G
authors.lastname: Mali
authors.forename: Miran
authors.initials: M
authors.lastname: Gaberšček
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003460:Crystallization; D003692:Delayed-Action Preparations / Q000737:chemistry; D007213:Indomethacin / Q000737:chemistry*; D008958:Models, Molecular; D016062:Porosity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D007213:Indomethacin