Pharmaceutical Cocrystallization: Engineering a Remedy for Caffeine Hydration

摘要: A systematic crystal engineering study was performed on the model pharmaceutical compound caffeine to prepare a cocrystal that, unlike caffeine, is physically stable at all relative humidities (RH). Six materials containing with one of several dicarboxylic acids are described herein. Methods cocrystallization included solution growth, neat solid-state grinding, and grinding solvent-drop addition. Crystal structures reported for total five cocrystals (with oxalic acid, malonic maleic glutaric acid), including two recently polymorphic cocrystals. In each these structures, predicted intermolecular hydrogen-bonding motif observed. The stability respect RH evaluated six materials. acid exhibits complete humidity over period weeks. Other demonstrate lesser degrees humidity.