基于溶解度参数法和差式扫描量热法优化筛选奥拉帕利固体分散体载体  

Optimization and screening of carrier for solid dispersion of olaparib based on the solubility parameter and differential scanning calorimetry

作　　者：严梦梦 吴秀娟 朱恒清 刘思远 袁熙敏 丁汉成 衡伟利 张建军[2] 钱帅[1] YAN Meng-meng;WU Xiu-juan;ZHU Heng-qing;LIU Si-yuan;YUAN Xi-min;DING Han-cheng;HENG Wei-li;ZHANG Jian-jun;QIAN Shuai(School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China;School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学中药学院,江苏南京211198 [2]中国药科大学药学院,江苏南京211198

出　　处：《药学学报》2022年第5期1486-1494,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82074029,82104401);中国博士后基金资助项目(2020M671665,2021M693517);国家药品监督管理局药品监管创新与评价基金项目(3342100010);中央高校基金资助项目(2632021ZD15)。

摘　　要：固体分散体是药物高度分散在载体材料中形成的分散体系,常用于改善难溶性药物的溶解度及溶出速率。药物与载体的混溶性是固体分散体溶出性能改善及产品稳定的关键,因此载体种类的选择及载药量的优化至关重要。本研究通过溶解度参数法和Flory-Huggins相互作用理论初步预测奥拉帕利(OLP)与不同载体(VA64、Soluplus、Plasdone S630和Kollidon K29/32)的混溶性,并结合差式扫描量热法(DSC)对药物和载体的混溶性进行实验评估,筛选出具有良好混溶性的载体材料。通过绘制药物与载体的混溶性相图,优选出两者的最佳比例。理论计算和实验评估表明,OLP与VA64的混溶性最佳,当载药量为30%时可同时满足较大载药量和物理稳定性的需求。偏光显微镜、X-射线衍射法、DSC和激光共聚焦拉曼光谱法表明,固体分散体中OLP呈无定形态分散在载体中。粉末溶出试验表明,与OLP晶体相比,其体外溶出度明显提高。本研究采用理论计算和DSC实验评估筛选载体,并得到药物与载体的最佳配比,为固体分散体载体的选择及用量的确定提供更为有效的研究策略。Solid dispersion,a dispersion system in which drug molecules are highly dispersed in carrier materials,has been commonly used to improve the solubility and dissolution rate of poorly soluble drugs.The miscibility between drug and carrier is crucial to improve the dissolution performance and stability of solid dispersion.Therefore,the selection of carrier types and the optimization of drug loading are very important.In the current study,the solubility parameter method and Flory-Huggins theory were used to predict the miscibility between olaparib(OLP)and different carriers(VA64,Soluplus,Plasdone S630 and Kollidon K29/32).Besides,the carrier material with good miscibility was experimentally screened by differential scanning calorimetry(DSC).The optimum of drug-carrier ratio was further performed based on the miscibility phase diagram of drug and carrier.Theoretical calculation and experimental evaluation showed that the miscibility of OLP and VA64 was the best,and the drug loading of 30%could meet the requirements of large drug loading and physical stability.Polarizing light microscope,X-ray powder diffraction,DSC and laser confocal Raman spectroscopy exhibited that OLP was amorphous form in the solid dispersion system.Powder dissolution test demonstrated that the solid dispersion showed significantly enhanced dissolution rate in comparison to crystalline OLP.In this study,theoretical calculation and experimental evaluation were used to screen the types of carriers and optimize the drug loading,which provides an efficient strategy for the selection of carrier and the amount used in solid dispersion.

关 键 词：固体分散体 奥拉帕利 载体 理论计算 实验评估 

分 类 号：R943[医药卫生—药剂学]