Moisture-induced limited recrystallization may not reduce the dissolution of amorphous solid dispersions: A case of nitrendipine

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.