一个预测系统:小分子添加剂对通过热挤出技术制备的无形固体分散物的特性有调节作用
Peiya Shen1, Chunfeng Zhang2, Enshi Hu1
1School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, PR China.
概括
小分子添加剂 (SMA) 用于通过防止再结晶和增强稳定性来改善无形固体分散 (ASD). 开发了一个预测系统来调节ASD属性,降低开发成本.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 计算化学计算化学
背景情况:
- 无形固体分散 (ASD) 具有可溶性优势,但由于聚合物的高度和溶液超和,因此面临重新结晶和减少溶解等挑战.
- 在ASD中,水友性聚合物可以增加高度,导致不稳定性和药物再结晶,损害治疗效果.
研究的目的:
- 研究一般公认安全 (GRAS) 清单中的小分子添加剂 (SMA) 的使用,以增强药物聚合物ASD的特性.
- 建立一个分子层面的理解SMA和ASD之间的相关性.
- 构建一个用于调节ASD属性的预测系统,重点关注稳定性和溶解.
主要方法:
- 使用汉森溶解性参数,弗洛里-哈金斯相互作用参数和差异扫描热量计来选SMA及其剂量.
- 使用X射线光电子光谱和吸附能量的计算 (Eabs) 进行表面分析,以评估湿度和稳定性.
- 分子动力学模拟,包括射线分布函数分析,以了解组件相互作用和溶解性能.
主要成果:
- 确定了影响湿度和稳定性的关键因素,包括ASD系统和溶剂之间的表面组分布和吸附能量.
- 确定组件之间的相互作用是溶解性能的关键.
- 通过模拟和固态表征,成功构建并验证了用于调节ASD属性的预测系统.
结论:
- SMAs可以有效地减轻再结晶的风险,并改善ASD的稳定性和溶解.
- 开发的基于分子动力学和固态特征的预测系统有效地指导SMA和ASD配方的选择.
- 这种方法大大减少了与ASDs药物开发前查相关的时间和经济成本.
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