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
赵朋 1李聪慧 2帅思祎 2杨兵 2张慧 2刘楠 2王增明 2王永军 3郑爱萍2
作者信息
- 1. 沈阳药科大学无涯创新学院,辽宁沈阳 110016;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
- 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
- 3. 沈阳药科大学无涯创新学院,辽宁沈阳 110016
- 折叠
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.
Abstract
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 theological 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 10 000 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Key words
rheology/hot melt extrusion/suvorexant/solid dispersion/glass transition temperature/viscosity引用本文复制引用
基金项目
国家重点研发计划资助项目(2023YFC2706100)
出版年
2024
NETL
NSTL
万方数据