Spontaneous Crystalline-to-Amorphous Phase Transformation of Organic or Medicinal Compounds in the Presence of Porous Media, Part 1: Thermodynamics of Spontaneous Amorphization

Spontaneous crystalline-to-amorphous phase transformation of organic or medicinal molecules in the presence of mesoporous materials has been observed, for which pathway was suggested to be via the vapor phase, that is, sublimation of the crystalline molecules followed by adsorption on the porous media. The objective of this paper is to rigorously evaluate this amorphization pathway and to study the thermodynamics of spontaneous amorphization. Mesoporous silicon dioxide (SiO2) was used as a model system. Physical mixtures of SiO2 and crystalline compounds were prepared and stored at 0% relative humidity (RH) and 40 degrees C. Loss of crystallinity of the model compounds was confirmed using powder X-ray diffraction and polarized light microscopy. Adsorption chamber was set up, in which naphthalene and SiO2 were stored, without physical contact, under reduced pressure at 0% RH and 40 degrees C. Data confirmed that the rate and extent of sublimation and adsorption of naphthalene were significant for amorphization to occur on a pharmaceutically relevant timescale. Furthermore, a thermodynamic model has been developed to explain spontaneous amorphization. This unique phase transformation phenomenon can be a simple and effective method to improve the aqueous solubility and bioavailability of poorly soluble drug molecules. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2801-2815, 2011