结合溶解和受控释放策略,制备带有阿尔本达的pH敏感固体分散:体外和体内研究
Dehai Su1, Mingyang Bai1, Chaoqun Wei1
1Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University (SCAU), Guangzhou, China.
这项研究开发了一种新的pH敏感固体分散阿尔本达 (ABZ),以改善其口服输送. 新配方增强了ABZ溶解性和肠道药物度,为治疗三病提供了一个有前途的替代方案.
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:
- 阿尔本达 (ABZ) 是一种BCSII类药物,对三毛病有效,但由于溶解性差和pH敏感性有限.
- 高剂量的ABZ可以导致发育性毒性,需要优化输送策略.
- 目前的口服配方在实现一致的治疗疗效方面面临挑战.
研究的目的:
- 开发和描述阿尔本达 (ABZ-pHs-SD) 的pH敏感固体分散,以改善口服.
- 与商业产品相比,评估新配方的溶解特征,药理动力学和肠道药物度.
- 评估ABZ-pHs-SD作为工业上可行的药物输送系统的潜力.
主要方法:
- ABZ被配制成一种pH敏感的固体分散剂,使用糖单酸盐 (GM) 和酸酸酸盐 (HPMC-AS).
- 描述涉及SEM,PXRD,DSC和FT-IR,以确认药物分散和状态.
- 在体外溶解,体内药理动力学和肠道药物度与商业ABZ配方进行了比较.
主要成果:
- ABZ-pHs-SD显著增加了ABZ的水溶性,增加了3.15倍.
- 该配方在弱性条件下表现出受控释放,并在酸性环境中防止释放.
- 与商业产品相比,体内研究显示ABZ-pHs-SD的Cmax较低,Tmax更高,肠道药物度增加,而不会影响生物可用性.
结论:
- ABZ-pHs-SD是一种有前途的药物输送策略,用于提高难溶性和pH敏感的阿尔本达的治疗疗效.
- 简单的制备方法凸显了这种固体分散方法的工业可行性.
- 这种配方提供了一个潜在的解决方案,以减少ABZ剂量频率和相关的毒性.
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