计算水溶性较差的弱的单质盐的pH溶性概况和pHmax
1Sanofi U.S., CMC Formulation, Synthetics Platform, 350 Water Street, MA 02141 Cambridge, USA.
International journal of pharmaceutics
|February 26, 2025
概括
这项研究引入了新的方程来预测制药盐的溶解度和pHmax,有助于选择最佳的药物盐形式,以改善生物可用性和稳定性,而无需合成.
科学领域:
- 制药科学 制药科学
- 物理化学 物理化学
- 药物开发 药物开发
背景情况:
- 制药盐增强水溶性较差的活性制药成分 (API) 的生物可用性.
- 盐的选择需要平衡超和的高溶解度与保质期的物理稳定性.
- 预测盐的特性,如pH-可溶性概况和最大pH (pHmax) 是至关重要的,但具有挑战性.
研究的目的:
- 为关键盐参数开发预测方程,特别是pH-可溶性概况和pHmax.
- 为了使得在常见电流的存在下,能够计算低于pHmax的盐溶性.
- 为了提供一个工具来评估盐形成者的风险,而不需要盐合成.
主要方法:
- 开发新的数学方程来建模pH-可溶性概况和pHmax.
- 利用现有的文献数据进行模型的实验验证.
- 开发模型与传统计算方法的比较.
主要成果:
- 该模型准确地预测了盐的溶解度,与实验数据有很好的一致性.
- 开发的方程对于水溶性较差,pKa值较低的基特别有效.
- 这项研究支持将盐的选择集中在足够的,而不是最大的溶解度上,以确保物理稳定性.
结论:
- 开发的方程为明智的药用盐选择提供了有价值的工具.
- 该模型有助于在药物开发过程的早期评估盐形成者的风险.
- 优化盐的选择包括平衡溶解度和物理稳定性,以防止对保质期的有害影响.
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