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Solubility is an important parameter with relevance to drug absorption. Poor solubility can result in erratic oral absorption and poor bioavailability. Of further interest, is the susceptibility of compounds to transform from one solid form to another with different physical properties. In this study, two different polymorphs of a proprietary Boehringer Ingelheim compound, BIX 011397 (polymorph III) and BIX 011398 (polymorph I) were investigated by the CheqSol (Chasing Equilibrium Solubility, patent applied for) method for equilibrium solubility measurement.1, 2 The method dissolves and partially reprecipitates ionizable compounds using a GLpKa/D-PAS titration system that can repeatably cycle the solution between a supersaturated and subsaturated state. Accurate solubility values are determined from the transition between the supersaturated solution (with solid precipitating) and the subsaturated system (with solid redissolving). The objective was to investigate the feasibility of detecting polymorphic conversions whilst performing these equilibrium solubility studies. Comparisons were made to traditional shake-flask measurements, and solids were characterized using TGA, DSC, microscopy and XRPD methods.
PTT-显微拉曼-石墨烯检测
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