超和的二甲基脂分散,以改善粉分子的口服生物利用性:阿普雷皮坦的案例研究
Ajay Sanjay Lale1, Arvind Sirvi1, Shubham Debaje1
1Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S Nagar, Punjab, India.
概括
聚合物增强的脂固体分散剂显著提高了阿普雷皮坦 (APT) 的生物制药性能. 这种方法促进药物释放,吸收,并减少食物的影响,为增强药物输送提供了一个有希望的策略.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 生物制药生物制药公司
背景情况:
- 阿普雷皮坦 (APT) 由于溶解度和溶解度低,其生物制药性能不佳.
- 固体分散是一种提高难溶性药物的可溶性和生物利用性的策略.
- 基于脂的固体分散为改善药物配方提供了潜力.
研究的目的:
- 研究将聚合物纳入脂基固体分散物的使用,以增强阿普雷皮坦的生物制药性质.
- 评估聚合物选择对药物沉抑制的影响.
- 评估优化的阿普雷皮坦固体分散的体外和体内性能.
主要方法:
- 使用微阵列板进行聚合物选,以确定最佳的沉抑制剂.
- 通过共同溶剂蒸发制备二进制 (BD) 和三进制 (TD) 脂分散物.
- 使用SEM,PXRD,FTIR和NMR进行固态特征.
- 在空腹和食状态模拟肠液 (FaSSIF/FeSSIF) 中进行体外溶解研究.
- 在仿生条件下的体外透研究.
- 在禁食状态下进行体内药理动力学评估.
主要成果:
- 确定HPMCAS是抑制药物沉的最佳聚合物.
- 无论是BD还是TD都显著增加了阿普雷皮坦的溶解 (FaSSIF中的4.8-9.9倍).
- TD减少了食物对阿普雷皮坦溶解的积极影响.
- 试验室透研究显示,BD (3.3x) 和TD (14x) 的稳定状态流量显著更高.
- 在体内研究表明,阿普雷皮坦与TD和BD的吸收增强 (Cmax增加2.1x和1.3x,AUC0-t增加2.3x和1.4x).
结论:
- 基于聚合物的脂分散有效地提高了阿普雷皮坦的生物制药性能.
- 开发的固体分散导致更好的溶解,透和口服吸收.
- 这种配方策略对改善阿普雷皮坦特等难溶药物的输送具有显著的前景.
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