再分散性高药负荷无形配方的设计:离子对非离子表面活性剂对加工和性能的影响
Mengqi Yu1, Hardeep S Oberoi1, Hitesh S Purohit1
1Research & Development, AbbVie Inc., North Chicago, Illinois 60064, United States.
Molecular pharmaceutics
|October 25, 2023
概括
使用维生素ETPGS,可以制备具有高药物负载 (>90%) 的工程无形纳米粒子 (ANP). 这些ANP保持生物可用性,同时减少对溶解不良药物的聚合物需求.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
背景情况:
- 无形固体分散 (ASD) 增强了口服药物的生物可用性,但通常需要高的聚合物含量 (<25%的药物负载).
- 在ASD的局部纳米粒子形成驱动超和,以改善药物吸收.
- 直接设计的无形纳米粒子 (ANP) 提供了一种减少聚合物使用的策略.
研究的目的:
- 用维生素ETPGS (TPGS) 作为稳定剂制备和描述高药载无形纳米粒子 (ANPs).
- 将TPGS稳定ANP与使用阳离子表面活性剂 (二硫酸盐) 制备的ANP进行比较.
- 评估表面活性剂选择对ANP属性和再分散行为的影响.
主要方法:
- 溶剂/抗溶剂纳米沉,有机溶剂去除和喷雾干燥用于ANP制备.
- 动态光散射,过剂强度测定,扫描电子显微镜和差分扫描热量计被用于表征.
- 模型化合物ABT-530用于用TPGS准备ANP.
主要成果:
- 使用TPGS成功制备了高药载荷ANP (<300nm).
- 描述揭示了纳米粒子表面特性受表面活性剂影响的差异 (TPGS与阳离子).
- 稳定剂的选择显著影响ANP的行为和再分散.
结论:
- 维生素ETPGS是一种有效的非离子表面活性剂,用于制备高药载荷无形纳米粒子.
- 了解表面活性剂的影响对于设计有效的高药载荷无形配方至关重要.
- 优化稳定剂可以导致减少聚合物数量,而不会影响生物可用性.
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