酮康唑固体分散体及共研磨物的制备及其体外溶出作用研究

目的:制备酮康唑固体分散体及其共研磨物并考察其体外溶出作用。方法:分别以聚乙二醇(PEG)、聚维酮(PVP)和泊洛沙姆(F68)作为载体材料,采用熔融法或溶剂法制备药物与载体不同比例(1∶1、1∶3、1∶5、1∶10)的酮康唑固体分散体;另制备药物与低取代羟丙基纤维素(L-HPC)不同比例(1∶0.5、1∶1、1∶1.5)的酮康唑共研磨物;研究各固体分散体和共研磨物的体外溶出情况,同时与酮康唑原料药进行比较。结果:与原料药比较,载药固体分散体和共研磨物可以显著提高酮康唑的溶出水平,且溶出速率随着载体比例的增加而增大,各固体分散体(1∶10)和共研磨物(1∶1.5)在20min时累积溶出率均大于90%,而原料药低于50%。结论:酮康唑制成固体分散体和共研磨物可以显著提高其体外溶出度。

Study on the Preparation and in Vitro Dissolution of Ketoconazole Solid Dispersion and Cogrinding Mixture

OBJECTIVE： To prepare Ketoconazole solid dispersions and cogrinding mixture, and to investigate dissolution rate in vitro. METHODS： Ketoconazole solid dispersion was prepared by melting or solvent evaporation methods using PEG, PVP, F68 as carrier materials with different proportion of drugs to carrier （ 1 ： 1, 1 ： 3, 1 ： 5, 1 ： 10）. Ketoconazole cogrinding mixture was prepared with different proportion of drugs to L-HPC （1 ： 0.5, 1 ： 1, 1 ： 1.5）. The in vitro dissolution rate of Ketoconazole solid dis- persions and cogrinding mixture were tested and compared with that of ketoconazole raw material. RESULTS： Compared with raw material, drug-loaded solid dispersion and cogrinding mixture could significantly improve the dissolution rate of ketoconazole with the proportion of carriers increased. Within 20 rain, all dissolution rates of solid dispersion （1 ： 10） and cogrinding mixture （ 1 ： 15） were above 90% while that of raw material was lower than 50% method can significantly increase the dissolution rate of ketoconazole CONCLUSION： Solid dispersion technology and cogrinding