Sarkar Anindita, Rohani Sohrab
Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, N6A 5B9, Ontario, Canada.
J Pharm Sci. 2015 Jan;104(1):98-105. doi: 10.1002/jps.24248. Epub 2014 Nov 18.
Cocrystal forming ability of antiviral drug acyclovir (ACV) with different coformers was studied. Three cocrystals containing ACV with fumaric acid, malonic acid, and DL-tartaric acid were isolated. Methods of cocrystallization included grinding with dropwise solvent addition and solvent evaporation. The cocrystals were characterized by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The crystal structure of the cocrystal with fumaric acid as conformer was determined by single crystal X-ray diffraction. Formation of supramolecular synthon was observed in the cocrystal. Stability with respect to relative humidity for the three cocrystals was evaluated. The aqueous solubility of the ACV-cocrystal materials was significantly improved with a maximum of malonic acid cocrystal, which was about six times more soluble at 35°C compared with that of parent ACV. The dissolution profile indicates that at any particular dissolution time, the concentration of cocrystals in the solution was higher than that of the parent ACV, and malonic acid cocrystals had a maximum release of about twice than the hydrated ACV.
研究了抗病毒药物阿昔洛韦（ACV）与不同共形成物的共晶形成能力。分离出了三种含阿昔洛韦与富马酸、丙二酸和DL-酒石酸的共晶。共结晶方法包括滴加溶剂研磨和溶剂蒸发。通过粉末X射线衍射、差示扫描量热法和热重分析对共晶进行了表征。以富马酸为共形成物的共晶的晶体结构通过单晶X射线衍射确定。在共晶中观察到超分子合成子的形成。评估了三种共晶在相对湿度方面的稳定性。ACV-共晶材料的水溶性显著提高，丙二酸共晶的水溶性提高最大，在35°C时其溶解度比母体ACV高约六倍。溶出曲线表明，在任何特定的溶出时间，溶液中共晶的浓度均高于母体ACV，丙二酸共晶的最大释放量约为水合ACV的两倍。
