拉帕替尼固体分散体的制备及体外溶出度研究  

Preparation and in vitro Dissolution of Lapatinib Solid Dispersion

作　　者：王喻华 冯菊红[1,2] 刘祺 孙锟辉[1,2] 王理想 何少男 胡学雷 WANG Yuhua;FENG Juhong;LIU Qi;SUN Kunhui;WANG Lixiang;HE Shaonan;HU Xuelei(School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430074,China;Key Laboratory of Green Chemical Process of Ministry of Education,Wuhan 430074,China)

机构地区：[1]武汉工程大学化工与制药学院,湖北武汉430074 [2]绿色化工过程教育部重点实验室,湖北武汉430074

出　　处：《化学与生物工程》2021年第8期39-43,54,共6页Chemistry & Bioengineering

基　　金：湖北省自然科学基金重点项目(2011CDA048)。

摘　　要：抗癌药物拉帕替尼水溶性差、生物利用度低。为了改善其溶解度,分别以亲水性高分子材料共聚维酮(CoPVP)、聚乙烯吡咯烷酮(PVPk30)和泊洛沙姆188(F68)为载体,采用溶剂法制备拉帕替尼固体分散体;以累积体外溶出度为评价指标,优化拉帕替尼固体分散体的制备工艺;通过X-射线衍射仪(XRD)、热重-差热分析仪(TGA-DSC)和扫描电镜(SEM)对拉帕替尼固体分散体进行了物相鉴别。结果表明,拉帕替尼以无定形态高度分散于载体PVPk30中;当拉帕替尼与载体PVPk30的质量比为1∶7、反应温度为60℃、反应时间为30 min时,拉帕替尼固体分散体的溶出效果最佳,累积体外溶出度可以达到89.98%,远高于拉帕替尼原料药(10.43%)和拉帕替尼与PVPk30的物理混合物(12.55%)。As an anti cancer drug,Lapatinib has poor water solubility and low bioavailability.To improve the solubility of Lapatinib,we prepared its solid dispersions(SD)by a solvent method by using three types of hydrophilic polymers,including copovidone(CoPVP),polyvinylpyrrolidone(PVPk30),and poloxamer 188(F68)as carriers.Moreover,we optimized the preparation process by using the cumulative in vitro dissolution as an evaluation index.Futhermore,we identified the phases of Lapatinib SD by X-ray diffraction(XRD),thermogravimetric analysis-differential scanning calorimetry(TGA-DSC),and scanning electron microscopy(SEM).The results show that Lapatinib is highly dispersed in carrier PVPk30 with amorphous form.When the mass ratio of Lapatinib to PVPk30 is 1∶7,the reaction temperature is 60℃,and the reaction time is 30 min,the dissolution effect of Lapatinib SD is the best,and the cumulative in vitro dissolution can reach 89.98%,which is much higher than that of Lapatinib(10.43%)and physical mixture of Lapatinib and PVPk30(12.55%).

关 键 词：拉帕替尼 固体分散体 体外溶出度 溶剂法 表征 

分 类 号：R944.9[医药卫生—药剂学]