在开发皮多格雷尔固体分散配方时采用体外基方法
Ehlimana Osmanović Omerdić1,2, Sandra Cvijić1, Jelisaveta Ignjatović1,3
1Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia.
Bioengineering (Basel, Switzerland)
|April 26, 2025
概括
这项研究优化了使用 in vitro-in silico 方法的克洛皮多格雷尔固体分散 (SD). 特定的聚合物配方显著提高了克洛皮多格雷尔的生物可用性和改善了药理动力学特征.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 药理动力学 药理动力学
背景情况:
- 克洛皮多格雷尔的生物可用性可能受到其药理动力学特征的限制.
- 固体分散 (SD) 技术提供了一种提高药物吸收的策略.
- 优化SD配方因子对于提高药物疗效至关重要.
研究的目的:
- 研究固体分散配方因子对克洛皮多格雷尔生物可用性和药理动学的影响.
- 开发和验证一个基于生理学的生物制药模型 (PBBM) 皮多格瑞尔.
- 为了预测克洛皮多格雷尔SDs的药理动力学性能,使用体外-在-的方法.
主要方法:
- 使用Poloxamer 407和copovidone在1:5和1:9的药物与聚合物比率下制备克洛皮多格雷尔固体分散剂.
- 在不同的pH条件下进行体外溶解试验.
- 开发和验证一种特定于克洛皮多格雷尔的生理学基础生物制药模型 (PBBM).
- 使用体外溶解数据作为PBBM的输入来进行药物动力学概况的in silico预测.
主要成果:
- 聚合物类型和比率显著影响了SDs中的克洛皮多格雷尔释放;高聚合物含量减少了释放.
- 与立即释放片相比,使用科波维 (1:5) 和波洛克萨默 (1:9) 的SD显示了药物吸收和生物可用性的100%以上的改善潜力.
- 波洛克萨默 (1:9) 配方可以通过促进远端肠道的吸收来减少药物动力学变异性,可能降低第一通代谢.
结论:
- 在体外-在体内方法是有效的开发和优化克洛皮多格雷尔固体分散配方.
- 特定的SD配方,特别是与科波维 (1:5) 和波洛克萨默 (1:9),可以显著提高克洛皮多格雷尔的生物可用性.
- 向远端肠道吸收可能是一个可行的策略,以改善克洛皮多格雷尔的药理动力学特征,减少变异性.
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