无形固体分散形成,以提高 Racemic 和 Enantiopure Praziquantel 的释放性能
Hector Polyzois1, Hanh Thuy Nguyen1, Benedito Roberto de Alvarenga Junior1
1Department of Industrial and Molecular Pharmaceutics, College of Pharmacy, Purdue University, West Lafayette, Indiana 47907, United States.
Molecular pharmaceutics
|September 18, 2024
概括
使用特定的聚合物开发PZQ的无形固体分散 (ASD),可显著提高药物释放和生物可用性. 这种方法为目前的PZQ片提供了一个有前途的替代方案,可能有助于改善杆菌病的治疗.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 药用化学 医学化学
背景情况:
- 全球有超过2.5亿人患有杆菌病,其主要治疗方法是praziquantel (PZQ).
- 目前的晶体种族PZQ (RS-PZQ) 配方的溶解和生物可用性较差,导致副作用和合规性问题.
- 关于使用无形固体分散 (ASD) 改善PZQ生物可用性的研究有限.
研究的目的:
- 研究RS-PZQ和R-PZQ无形固体分散物的制备和性能.
- 确定适合抑制结晶和增强PZQ释放的聚合物.
- 评估通过溶剂蒸发 (SE) 和热挤出 (HME) 制备的ASD的物理稳定性和药物释放特性.
主要方法:
- 进行核化诱导时间实验,以选RS-PZQ和R-PZQ的聚合物.
- 使用溶剂蒸发 (SE) 和热挤出 (HME) 用精选的纤维素基聚合物 (HPMCAS-MF和HPMC E5 LV) 制备无形固体分散 (ASD).
- 使用X射线粉末衍射 (XRPD) 证实ASD无形性质,并在加速条件下评估稳定性.
主要成果:
- 鉴定出基甲基纤维素酸酸盐 (HPMCAS-MF) 和基甲基纤维素 (HPMC E5 LV) 是有效的结晶抑制剂.
- 与HPMCAS-MF配制的SE ASDs与商业PZQ片相比,显示药物释放显著更快 (增加6倍).
- SE R-PZQ ASDs的药物释放与RS-PZQ ASDs相比较或优越,这表明对抗体特定配方的潜力.
结论:
- 无形固体分散剂 (ASD),特别是SE使用HPMCAS-MF制备的分散剂,显著改善了普拉齐量子 (PZQ) 的溶解和释放.
- 开发的ASD表现出良好的物理稳定性,表明它们适合制药配方.
- 在自闭症患者中用活性R-反体 (R-PZQ) 配方提供了一个有希望的策略,以克服当前PZQ治疗的局限性并提高患者的服从性.
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