流变学指导热熔挤出技术制备苏沃雷生-共聚维酮固体分散体  

Rheology guided the preparation of suvorexant-copovidone solid dispersions via hot melt extrusion technology

作　　者：赵朋 李聪慧 帅思祎 杨兵 张慧 刘楠 王增明 王永军[1] 郑爱萍 ZHAO Peng;LI Cong-hui;SHUAI Si-yi;YANG Bing;ZHANG Hui;LIU Nan;WANG Zeng-ming;WANG Yong-jun;ZHENG Ai-ping(Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China;State Key Laboratory of National Security Specially Needed Medicines,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]沈阳药科大学无涯创新学院,辽宁沈阳110016 [2]军事医学研究院国家安全特需药品全国重点实验室,北京100850

出　　处：《药学学报》2024年第8期2396-2403,共8页Acta Pharmaceutica Sinica

基　　金：国家重点研发计划资助项目(2023YFC2706100)。

摘　　要：药物与载体材料的流变学性质对于固体分散体的处方和工艺开发具有广泛的指导意义。本研究以苏沃雷生为模型药,共聚维酮为载体材料,对不同药物载体比例的物料流变学特性进行了系统研究,为确定固体分散体的处方和工艺提供了充分依据。振荡温度扫描结果可得最佳的苏沃雷生-共聚维酮比例为1∶4,若比例大于1∶4,物料玻璃态转化温度增加趋势显著,同时固体分散体增溶效果会呈下降趋势。振荡温度扫描与振荡温度扫频结果可得,当挤出温度大于150℃时,物料黏度低于10 000 Pa·s,熔体可顺利挤出;同时结合溶出结果最终得到最佳的挤出温度为160~180℃。最后通过流变学特性研究指导开发的苏沃雷生片在多介质中溶出均与市售片剂Belsomra相似。因此,流变学研究可以从机制层面筛选优化苏沃雷生固体分散体处方与工艺,对提高热熔挤出制备固体分散体研发成功率及缩短研发周期具有重要意义。The rheological properties of drug and carrier materials have a wide range of guiding significance for the formulation and process development of solid dispersions.In this study,the rheological properties of materials with different drug carrier ratios were systematically studied with suvorexant as the model drug and copovidone as the carrier material,which provided a sufficient basis for determining the formulation and process of solid dispersions.The optimal suvorexant-copovidone ratio obtained by oscillating temperature scanning was 1∶4.If the ratio is greater than 1∶4,the glass transformation temperature of the material will increase significantly,and the solubilization effect of the solid dispersion will show a downward trend.The results of oscillation temperature scanning and oscillation temperature sweep can show that when the extrusion temperature is greater than 150℃,the viscosity of the material is less than 10000 Pa·s,and the melt can be extruded smoothly,and the best extrusion temperature of 160−180℃can be obtained by combining the dissolution results.Finally,the dissolution of suvorexant tablets guided by rheological property studies in multiple media is similar to that of the commercially available tablets Belsomra.Therefore,rheological studies can screen and optimize the formulation and process of suvorexant solid dispersions at the mechanism level,which is of great significance to improve the success rate of R&D and shorten the R&D cycle of solid dispersions prepared by hot melt extrusion.

关 键 词：流变学 热熔挤出 苏沃雷生 固体分散体 玻璃态转化温度 黏度 

分 类 号：R943[医药卫生—药剂学]