4种他克莫司固体分散体的体外特性研究_顾希平.pdf

4 ＊ 顾希平,吴君华,任飞亮, 裴元英 (, 200032) :　采用固体分散技术, 比较4种不同载体对他克莫司 溶解度和体外溶出度 作用。　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(PMC)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 存在状态。　各种固 体分散体均能大大增加他克莫司 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。 　PVP 或 PMC 作为载体制成固体分散体, 对增加他克莫司 溶解度和体外溶出度 效果优于F68和S40。 :他克莫司;泊洛沙姆 188;聚维酮;硬脂酸聚烃氧(40);羟丙甲纤维素;固体分散体 :R944　　　:A　　　:1001-2494(2006)07-0523-04 Studies on Preparation and in vitro Evaluation of Tacrolimus Solid Dispersions ＊ GU Xi-ping, WU Jun-hua, REN Fei-liang, PEI Yuan-ying (College of Pharmacy, Fudan University, Shanghai 200032, China) ABSTRACT:OBJECTIVE　To compare the solubility and in vitro dissolution of four tacrolimus-carrier solid dispersions.MET ODS　 Tacrolimus solid dispersions were prepared respectively with solvent evaporation-fusion method or solvent method using F68, S40, PVP and PMC as carriers.The solubility and in vitro dissolution characteristics of pure drug and solid dispersions in water were studied.DSC and XRDwere 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.CONCLU- SION　The effects of PVP and PMC as carriers of solid dispersions to increase the solubility and in vitro dissolution of tacrolimus solid dis- persions are better than F68 and S40. KEY WORDS:tacrolimus;F68;PVP;S40; PMC;solid dispersion 　　(tacrolimus, FK-506) 1　 (), DSC204 ();D/max- , A(CsA) rB 12kW X ( ,CsA 10 ～100 , );(Thermo Nicolet, [1] 。,、 USA);ZRS-8 ( 、;, );(SPD-10A、LC-10AT [2] [3] , 。1987 , onbo 、 T-230A ,);CQ50 (PMC), ()。 、 、( [4] , 04