目的采用固体分散技术,比较4种不同载体对他克莫司的溶解度和体外溶出度的作用。方法分别以泊洛沙姆188(F68)、聚维酮(PVP)k29/32、硬脂酸聚烃氧(40)酯(S40)和羟丙甲纤维素(HPMC)为载体,采用溶剂-熔融法或溶剂法,制备他克莫司固体分散体。测定溶解度,进行体外溶出试验,并采用DSC、XRD法鉴别药物在固体分散体中的存在状态。结果各种固体分散体均能大大增加他克莫司的溶解度,加快其体外溶出。他克莫司在固体分散体中可能以无定型态或分子状态存在。结论PVP或HPMC作为载体制成固体分散体,对增加他克莫司的溶解度和体外溶出度的效果优于F68和S40。

OBJECTIVE To compare the solubility and in vitro dissolution of four tacrolimus-carrier solid dispersions.METHODS Tacrolimus solid dispersions were prepared respectively with solvent evaporation-fusion method or solvent method using F68,S40,PVP and HPMC as carriers.The solubility and in vitro dissolution characteristics of pure drug and solid dispersions in water were studied.DSC and XRD were used to determine the status of tacrolimus in solid dispersions.RESULTS The solubility and in vitro dissolution of all tacrolimus solid dispersions were increased significantly.Tacrolimus existed as amorphous or molecular state in tacrolimus solid dispersions.CONCLUSION The effects of PVP and HPMC as carriers of solid dispersions to increase the solubility and in vitro dissolution of tacrolimus solid dispersions are better than F68 and S40.