结晶度
过饱和度
溶解
成核
溶解度
化学工程
无定形固体
材料科学
Crystal(编程语言)
聚合物
结晶
吸附
扫描电子显微镜
晶体生长
结晶学
化学
有机化学
复合材料
程序设计语言
工程类
计算机科学
作者
Dana E. Moseson,Andrew S. Parker,Stephen P. Beaudoin,Lynne S. Taylor
标识
DOI:10.1016/j.ejps.2020.105276
摘要
The solubility advantage of amorphous solid dispersions (ASDs) is contingent upon supersaturation being generated and maintained. If crystals are present within an ASD, these crystals directly result in lost solubility advantage, and may also seed crystal growth leading to desupersaturation. The goal of this study was to evaluate the impact of residual crystals on ASD supersaturation profiles. Indomethacin-copovidone (PVPVA) ASDs with different levels of residual crystallinity were manufactured by hot melt extrusion (HME). PVPVA at 5 and 50 µg/mL was found to be a highly effective nucleation and crystal growth inhibitor of indomethacin at high supersaturation. Evidence of polymer adsorption onto indomethacin crystals was observed by atomic force microscopy and scanning electron microscopy. HME ASDs containing 0-25% residual crystallinity demonstrated lost solubility advantage, along with minimal desupersaturation during non-sink dissolution testing. While bulk seeds did not properly represent the impact of residual crystals, extensive polymer adsorption onto residual seed crystals resulted in poisoned crystal growth, limiting the potential dissolution performance consequences. Several risk factors related to the presence of residual crystallinity were identified: polymeric crystal growth inhibition effectiveness, seed properties, and supersaturation conditions.
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