通过通过热挤出 (SEDEX) 在自乳化输送系统中通过固体和液体料进行低剂量卡维迪洛尔连续制造的比较
Ožbej Zupančič1, Josip Matić1, Aygün Doğan1
1Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, Austria.
Pharmaceuticals (Basel, Switzerland)
|October 26, 2024
概括
固体自乳化药物输送系统 (SEDDS) 的热挤压 (HME) 使用预溶解的卡维迪醇可确保药物的均分配和稳定的制造工艺. 这种连续制造方法为水溶性较差的化合物提供了改善的药物输送.
科学领域:
- 制药技术 制药技术 制药技术
- 药物输送系统 药物输送系统
- 连续制造 连续制造 连续制造
背景情况:
- 固体自乳化药物递送系统 (SEDDS) 对于改善水溶性差的药物的生物可用性至关重要.
- 热挤出 (HME) 是一种有前途的连续制造技术,用于生产固体SEDDS.
- 优化低剂量药物的HME过程需要仔细考虑药物整合方法.
研究的目的:
- 为了比较两个试点规模的HME方法,用于制造含有低剂量卡维迪洛的固体SEDDS.
- 评估药物合并 (粉末与预溶解) 对药物分发和可处理性的影响.
- 评估不同聚合物 (Kollidon® VA64和Soluplus®) 配制的固体SEDDS的性能.
主要方法:
- 卡维迪醇是一种水溶性较差的模型药物,在低度 (0.5-1.0%w/w) 中被纳入液体SEDDS配方中.
- 两种HME加工方法进行了比较:将卡维迪醇作为粉末加入与在液体SEDDS中预溶解.
- 药物分布,过程参数 (扭矩),辅助剂兼容性 (DSC,WAXS) 和自我乳化性能 (滴滴大小,时间,温度依赖性) 被评估.
主要成果:
- HME成功地生产了可加工的固体SEDDS,其SEDDS含量高达20% w/w.
- 在SEDDS中预溶解卡维迪醇,导致药物在挤出物中分布均,与粉末合并方法不同.
- SEDDS配方表现出塑化效应,将HME过程扭矩降低高达50%.
- 使用Kollidon® VA64的固体SEDDS显示出快速的自我乳化 (在15分钟内) 与稳定的液滴大小 (150-200纳米).
- 使用Soluplus®的固体SEDDS表现出较慢的乳化 (超过60分钟) 和取决于温度的滴滴大小增加,表明潜在的相位逆转.
结论:
- 通过HME连续制造固体SEDDS对于低剂量,水溶性较差的药物是可行的.
- 在SEDDS配方中提前溶解药物对于在HME期间实现均药物分配至关重要.
- 基于Kollidon® VA64的固体SEDDS提供了稳定高效的药物输送系统,具有强大的自我乳化特性.
- 聚合物的选择显著影响固体SEDDS的自我乳化性能和温度灵敏度.
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