As a promising strategy, amorphous solid dispersion (ASD) technology has been widely studied and employed. However, moisture affects the physical stability of ASD, leading to phase separation and recrystallization. This study aims to investigate the moisture-induced physical instability of the nitrendipine (NTD) ASD systems from apparent phenomenon to molecular mechanism. The critical relative humidity (CRH) of the ASD was identified as 50% RH through a dynamic vapor sorption study. After being stored above the CRH, ASDs exhibited obvious phase separation and recrystallization, owing to water competition hydrogen bond as evidenced by molecular docking. After 75% RH exposure, the ASD underwent obvious recrystallization thereafter the dissolution was reduced. However, the dissolution of ASD samples stored at 60% RH did not decrease obviously. This study helps to understand the environment humidities for ASD physical stability and gives hints at the relation between recrystallization and dissolution in the ASD system.

中文翻译：

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水分引起的有限重结晶可能不会减少无定形固体分散体的溶解：以尼群地平为例

作为一种有前景的策略，非晶固体分散体（ASD）技术已被广泛研究和应用。然而，水分会影响 ASD 的物理稳定性，导致相分离和重结晶。本研究旨在从表观现象到分子机制研究尼群地平 (NTD) ASD 系统由水分引起的物理不稳定性。通过动态蒸汽吸附研究，ASD 的临界相对湿度 (CRH) 被确定为 50% RH。分子对接证明，在 CRH 之上储存后，由于水竞争氢键，ASD 表现出明显的相分离和重结晶。75%RH暴露后，ASD发生明显的再结晶，随后溶解减少。然而，在60%RH下保存的ASD样品的溶出度并没有明显下降。这项研究有助于了解 ASD 物理稳定性的环境湿度，并提示 ASD 系统中重结晶和溶解之间的关系。