在半孔中含有大量的脂性化合物,以提高溶解性和溶解性能
Marvin Benedikt Brenner1, Matthias Wüst2, Martin Kuentz3
1University of Bonn, Pharmaceutical Institute, Department of Pharmaceutics, Gerhard-Domagk-Str. 3, 53121 Bonn, Germany.
International journal of pharmaceutics
|February 28, 2024
概括
将难以溶解的药物加载到半孔中,提高了它们的稳定性和溶解性. 这种先进的配方策略显著提高了高脂性活性药物成分 (API) 的性能,优于现有的产品.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 药物运输 药物运输 药物运输
背景情况:
- 溶性较差的活性药物成分 (API) 在载体聚合物中通常具有有限的溶性,导致药物负载较低和稳定性降低.
- 高脂性API (log D7.4 > 8) 由于溶解性差,因此存在重大制剂挑战.
- 半孔二氧化载体提供了一个有前途的方法,以非晶体形式稳定API,增强溶解.
研究的目的:
- 为了研究将高脂性API加载到中孔性二氧化载体中.
- 为了评估中等孔性二氧化配方对API稳定性,溶解性和溶解性能的影响.
- 为了与商业产品比较中孔二氧化配方的性能.
主要方法:
- 在Syloid® XDP 3050和Silsol® 6035中介孔载体中装载辅酶Q10 (CoQ10),阿斯坦丁 (ASX),普罗布科尔 (PB) 和卢梅芬 (LU).
- 评估API加载配方的物理稳定性和非晶体形式.
- 在生物相关介质中确定平衡溶解度,并在两相溶解研究 (BiPHa+) 中确定性能.
- 在混合度和实验色谱方法的in silico计算,以分析药物-相互作用.
主要成果:
- 配方在非晶体形式中实现了物理稳定性,药物负载高达50%.
- 增加的药物负载显著提高了生物相关介质的平衡溶解度.
- 在生物相关溶解研究中,中孔性二氧化配方表现出更好的性能,特别是对于CoQ10和ASX.
- CoQ10和ASX配方的表现优于现有的商业产品.
结论:
- 半孔二氧化载体有效地稳定不溶性,高脂性API在非晶体状态.
- 在中孔中配制显著提高了溶解性和溶解性,从而提高了体外性能.
- 这种方法为当前对具有挑战性的API,特别是CoQ10和ASX等天然产品的配方提供了优质的替代方案.
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