预测计算模型用于评估共磨对药物溶解的影响
Nicolas Pätzmann1, Patrick J O'Dwyer2, Josef Beránek3
1School of Pharmacy, University College Cork, Cork, Ireland; Department Preformulation and Biopharmacy, Zentiva, k.s., Prague, Czechia.
概括
共同研磨可显著提高药物溶解率的难以溶解的化合物. 新的模型准确地预测了使用药物特性 (如颗粒大小和溶解度) 的溶解改善,有助于早期配方开发.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 物理化学 物理化学
背景情况:
- 共磨是一种提高水溶性较差药物的溶解率的关键技术,对于改善药物的吸收至关重要.
- 在预测模型中存在一个显著的差距,用于量化通过共同研磨实现的溶解率改进.
- 了解和预测这些改进对于有效的药物配方开发至关重要.
研究的目的:
- 开发和验证定量模型,以预测在共磨后,水溶性较差的药物的溶解率的增加.
- 确定影响共同研磨在增强溶解效果的关键药物特性.
- 建立用于指导早期制药配方的计算工具.
主要方法:
- 使用生物相关溶解设置对29种不同晶体药物的选,在与Polyvinylpyrrolidone K25共同和物理混合的混合物中进行选.
- 使用带有变量选择的部分最小平方 (PLS) 回归来预测在15分钟和60分钟的共同磨粉溶解比率 (COMDR).
- 开发基于PLS模型识别的最有影响力的药物特性的多重线性回归方程.
主要成果:
- PLS模型准确地预测了COMDR15分钟 (R2=0.82,Q2=0.77) 和COMDR60分钟 (R2=0.87,Q2=0.84) 的时间.
- 使用三个关键药物特性的多重线性回归模型显示,COMDR15分钟 (R2 = 0.83) 和COMDR60分钟 (R2 = 0.84) 的高预测能力.
- 最有影响力的预测变量是药物颗粒的中位数大小,计算的logD6.5,Kappa 3描述符和24小时后的明显溶解度.
结论:
- 同是一种可行的策略,可以显著提高水溶性较差的药物的溶解率.
- 基于特定药物的物理化学性质的预测模型可以准确地预测来自共同研磨的溶解增强.
- 这些开发的模型作为优化药物配方在早期开发阶段的有价值的计算工具.
相关概念视频
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