计算支持探索具有挑战性的药物的三级固体分散使用coformer和基烯纤维素
Andreas Niederquell1, Susanne Herzig1, Monica Schönenberger2
1Institute for Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, School of Life Sciences FHNW, Hofackerstr. 30, 4132 Muttenz, Switzerland.
Molecular pharmaceutics
|October 10, 2024
概括
计算建模有助于为具有挑战性的药物开发稳定的无形固体分散. 这种方法预先选择辅助剂,提高配方稳定性并降低结晶风险.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 计算化学计算化学
背景情况:
- 许多无形药物配方面临着稳定性挑战.
- 开发稳定的无形固体分散对于不易溶解的化合物至关重要.
研究的目的:
- 为了探索稳定无形药物的三元固体分散.
- 引入一种计算方法来预选辅助剂.
- 评估溶解度参数间隔和COSMO-RS理论在配方开发中的有效性.
主要方法:
- 使用基烯纤维素作为聚合物和dl-/l-酸作为辅助剂.
- 采用可溶性参数间隔 (可溶性参数的重叠范围,ORSP) 和COSMO-RS用于in silico选.
- 进行热挤出用于配方制备.
- 使用批量分析和先进显微镜 (聚焦激光扫描,原子力显微镜) 评估物理稳定性.
主要成果:
- 在子选成功预测了稳定的配方.
- 用dl-酸和l-酸在基烯基纤维素中的三级固体分散物在3个月内没有显著的药物结晶.
- 在l-酸配方中的微小表面结晶是由于湿度.
结论:
- 拟议的计算方法与小规模挤出相结合,显示出开发具有挑战性的药物的稳定配方的前景.
- 这种方法可以帮助有效预选无形固体分散物的辅助剂.
- 需要进一步的研究来充分优化这种配方策略.
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