通过纳入复合物 (β-cyclopodextrin和hydroxypropyl β-cyclopodextrin) 提高阿皮克萨班的可溶性和溶解率,并计算其纳入复合物的计算
Zainab N Salman1, Israa Al-Ani1, Khaldun M Al Azzam1
1Pharmacological and Diagnostic Research Center (PDRC), Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan.
ADMET & DMPK
|November 8, 2023
概括
这项研究通过使用氧贝塔-环氧德 (HPβCD) 纳入复合物增强了阿皮克萨班 (AP) 的溶解性和溶解. 优化的AP-HPβCD复合物显著改善了口服药物的生物可用性.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 物理化学 物理化学
背景情况:
- 阿皮克萨班 (AP) 是一种口服抗凝剂和X因子抑制剂.
- AP具有较差的水溶性,溶解率和生物可用性.
- 提高AP的溶解度对于提高其治疗疗效至关重要.
研究的目的:
- 为了提高阿皮克萨班 (AP) 的水溶性和溶解率.
- 通过复杂化增强AP的口服生物可用性.
- 准备和表征与β-cyclodextrin (βCD) 和基基β-cyclodextrin (HPβCD) 的AP的包括综合体.
主要方法:
- 使用制,溶剂蒸发和喷雾干燥方法制备了阿皮克萨班 (AP) 纳入复合物.
- 综合体的特点是FTIR,DSC和药物含量分析.
- 阶段溶解性研究,紫外线光谱测量和计算机模拟 (对接) 被使用.
主要成果:
- 阶段溶解性研究表明,HPβCD的AP溶解性显著增加 (从54×10-3 mmol/L到66 mmol/L).
- 复杂化导致更高的溶解率,在一小时内95%的AP释放,而自由AP则为60% (p<0.05).
- 计算机对接支持形成稳定的1:1AP-cyclopodextrin复合体.
结论:
- AP-HPβCD复合物,特别是1: 2重量比,显著提高了AP的水溶性.
- 这种复杂化有效地提高了apixaban的体外溶解率.
- 开发的包容复合物有可能改善apixaban的口服生物可用性.
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