固化材料介孔二氧化硅对西罗莫司自微乳体外释放性能的影响及机制研究  

Effects of Solidified Material Mesoporous Slilica on in vitro Release Performance of Sirolimus Self-microemulsifying Drug Delivery System and Mechanism Research

作　　者：张灵娜 张雪婷 陈旭 周欣 宋洪涛 Zhang Lingna;Zhang Xueting;Chen Xu;Zhou Xin;Song Hongtao(Department of Pharmacy,900th Hospital of Joint Logistics Team of the PLA,Fuzhou 350025China)

机构地区：[1]中国人民解放军联勤保障部队第九〇〇医院药剂科,福州350025

出　　处：《中国药师》2022年第3期389-395,共7页China Pharmacist

基　　金：福建省自然科学基金面上项目(编号:2019Y0071);中国人民解放军联勤保障部队第九OO医院院立课题(编号:2020L16)。

摘　　要：目的:对西罗莫司(SRL)固体自微乳的体外溶出行为进行研究,明确不同结构的介孔二氧化硅(MS)对西罗莫司自微乳(SRL-SMEDDS)释放的影响。方法:制备不同官能团修饰的介孔二氧化硅固化西罗莫司自微乳制剂SRL-SMEDDS-MS(-R),使用小杯法进行体外溶出试验,通过计算自微乳的扩散效率、差式扫描量热法(DSC)和X-射线光电子能谱(XPS)考察自微乳在介孔硅中的释放机制。结果:在0.4%十二烷基硫酸钠(SDS)介质中,不同的SRL-SMEDDS-MS(-R)溶出度的大小排序为甲基修饰≈羧基修饰>羟基修饰>氨基修饰(SRL-SMEDDS-MS-M≈SRL-SMEDDS-MS-C> SRL-SMEDDS-MS-H> SRL-SMEDDS-MS-A),在水溶液中SRL-SMEDDS-MS-M和SRL-SMEDDS-MS-H的溶出度显著降低。SRL-SMEDDS-MS-A在水和0.4%SDS中均溶出困难,DSC和XPS结果证明SRL与MS-A存在强烈的氢键作用力。结论:表面官能团在SRL-SMEDDS-MS(-R)的药物释放中起着至关重要的作用,MS-M和MS-C可显著提高SRL的体外溶出度。Objective: To study the in vitro dissolution behavior of sirolimus(SRL) solid self-microemulsion, and to clarify the effects of slilica nanoparticles with different mesoporous structures on the release performance of sirolimus self-microemulsifying drug delivery system. Methods: The SRL-SMEDDS-MS(-R) with different functional groups were prepared, and the in vitro dissolution test was carried out by the small cup method. The release mechanism of self-microemulsion in mesoporous silica was investigated by calculating the diffusion efficiency of self-microemulsion, differential scanningcalorimetry(DSC) and X-ray photoelectron spectroscopy(XPS). Results: The order of SRL release in 0.4% SDS solution was SRL-SMEDDS-MS-M≈ SRL-SMEDDS-MS-C>SRL-SMEDDS-MS-H>SRL-SMEDDS-MS-A,and the dissolution rate of SRL-SMEDDS-MS-M and SRL-SMEDDS-MS-H decreased significantly in water solution. SRL was very difficult to release from SRL-SMEDDS-MS-A, and DSC and XPS results proved that SRL and MS-A had strong hydrogen bonding force. Conclusion: Surface functional groups play a vital role in the drug release of SRL-SMEDDS-MS(-R), and MS-M and MS-C can significantly improve the in vitro dissolution of SRL.

关 键 词：西罗莫司 自微乳化给药体系 介孔二氧化硅 体外溶出度 表面修饰 

分 类 号：R944.9[医药卫生—药剂学]