基于基基纤维素的溶球加快了阿普雷皮坦的溶解,并与其超和相结合,用于口服输送
Jan Kožák1, Paul Bühlbecker1, Annika Rautenberg1
1Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany.
概括
使用低粘度基纤维素 (HPC) 的喷冷干燥 (SFD) 制造了阿普雷皮坦的无形固体分散物. 这些快速溶解的粉末改善了大鼠的口服药物输送和生物可用性.
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
- 材料科学 材料科学 材料科学
背景情况:
- 喷雾冷干燥 (SFD) 提供了一种生产具有治疗潜力的自由流动的冷解粉末的方法.
- 无形固体分散 (ASDs) 增强了水溶性较差的药物的口服生物可用性.
- 阿普雷皮坦是一种水溶性较差的药物,需要先进的配方策略才能有效地口服.
研究的目的:
- 使用二甲基硫氧化物作为喷雾溶剂制造非水性SFD颗粒的阿普雷匹坦.
- 创建无形固体分散 (ASDs) 以改善阿普雷皮坦口服.
- 评估低粘度基纤维素 (HPC) 等级对粉末特性,稳定性,溶解性和药理动学的影响.
主要方法:
- 使用二甲基硫氧化物和低粘度HPC等级 (HPC-SSL,HPC-UL) 采用非水性喷雾冷干燥 (SFD).
- 准备了具有不同固体含量 (5%,10%),药物辅助剂比率 (20/80,40/60,100/0) 的配方,并与造的ASD相比较.
- 分析包括粒子形态,存储稳定性 (25°C12个月),pH1.2的体外溶解,以及在老鼠体内药理学研究.
主要成果:
- SFD产生了自由流动的粉末,平均颗粒大小在300-500μm之间.
- 实现了无形配方,保持稳定12个月.
- 在pH值1.2的溶解研究显示过和,在某些比率下,度高达和度的四倍.
- 在生体内对大鼠进行的研究显示,tmax为2.5-4小时,Cmax为1.04-1.24μg/ml,AUC为5.4-8.1μg*h/ml.
- 观察到几何粒子密度下降和生物利用率增加之间的潜在关系.
结论:
- 低粘度HPC等级是非水性SFD的合适辅助剂.
- 这种方法有效地产生无形,迅速溶解,低密度的阿普雷皮坦粉末.
- 开发的SFD方法增强了水溶性较差的化合物的口服药物输送.
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