在现场通过聚合物喷雾干燥进行共结晶,作为防止共结晶解离的策略
ShiZhe Shao1,2, Michael W Stocker1,2,3, Salvatore Zarrella4
1School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin D02 PN40, Ireland.
Molecular pharmaceutics
|August 18, 2023
概括
聚合物显著提高了在晶体固体分散 (CSDs) 中的双烯酸-l-烯酸共晶体 (DPCC) 的物理稳定性. 即使添加1%重量的聚合物,也可以防止高湿度下的共晶解离,而PVP和PVPVA提供了更好的保护.
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:
- 狄克洛芬酸-l-合晶 (DPCC) 的物理稳定性很差,特别是在潮湿的条件下.
- 晶分裂对药物配方和输送构成挑战.
研究的目的:
- 研究各种聚合物对通过联合喷雾干燥制备的共晶体解离的影响.
- 为了评估二二烯酸-l-合晶 (DPCC) 在不同聚合物的晶体固体分散 (CSD) 中的物理稳定性.
主要方法:
- 联合喷雾干燥API,联合制造器和聚合物,以形成CSD.
- 太赫兹拉曼光谱 (THz Raman) 和粉末X射线衍射 (PXRD) 用于监测共晶解离.
- 现场拉曼探测器用于缓冲区和水中的实时解离监测.
主要成果:
- DPCC解离是通过水介导的,在40°C和95%的RH下,在18小时内超过60%的解离.
- 在同样的条件下,将1%重量的聚合物纳入CSD有效地防止了DPCC解离.
- 使用聚乙烯利 (PVP) 和聚乙烯利1-联合乙酸 (PVPVA) 的CSD显示出优异的稳定性,在7天后仍然未分离或部分稳定.
结论:
- 聚合物显著提高了CSD中DPCC的物理稳定性,防止了水媒介解离.
- 喷雾干燥促进了高效的分子水平混合,现场聚合物凝形成了保护性屏障.
- 用PVP和PVPVA等特定聚合物的CSD为制药应用提供了更高的稳定性和更好的动态溶解性.
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