Shah J C, Chen J R, Chow D
Department of Pharmaceutical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, USA.
Drug Dev Ind Pharm. 1999 Jan;25(1):63-7. doi: 10.1081/ddc-100102142.
Etoposide, an anticancer drug, has low oral bioavailability because of low aqueous solubility, slow dissolution rate, and instability in acidic pH. Our objective was to enhance the aqueous solubility and dissolution rate of etoposide by polymorph formation. Preparation of various polymorphs of etoposide was attempted by crystallizing etoposide from organic solvents. Physicochemical properties of the crystals, namely, crystal habit, thermal behavior with hot-stage microscopy, thermal analysis by differential scanning calorimetry, IR spectrum, and solubility and dissolution rates, were examined. Based on the physicochemical characteristics, a metastable polymorph of etoposide was identified when it was crystallized from isopropanol. The metastable polymorph had an equilibrium solubility and intrinsic dissolution rate of 221 micrograms/ml and 16.3 micrograms/min/cm2, respectively; 1.9 and 1.7 times that of etoposide powder at 25 degrees C, respectively.
依托泊苷是一种抗癌药物，由于其水溶性低、溶解速度慢以及在酸性pH值下不稳定，口服生物利用度较低。我们的目标是通过形成多晶型物来提高依托泊苷的水溶性和溶解速度。尝试通过从有机溶剂中结晶依托泊苷来制备其各种多晶型物。研究了晶体的物理化学性质，即晶体习性、热台显微镜下的热行为、差示扫描量热法进行的热分析、红外光谱以及溶解度和溶解速度。基于物理化学特性，当依托泊苷从异丙醇中结晶时，鉴定出一种亚稳多晶型物。该亚稳多晶型物在25℃时的平衡溶解度和固有溶解速度分别为221微克/毫升和16.3微克/分钟/平方厘米；分别是依托泊苷粉末在25℃时的1.9倍和1.7倍。
