Effects of Temperature and Ionic Strength of Dissolution Medium on the Gelation of Amorphous Lurasidone Hydrochloride.

PURPOSE: Amorphous lurasidone hydrochloride (LH) showed decreased dissolution behavior in comparison to crystalline LH owing to gelation during dissolution as reported in our previous study. The current study aims to investigate external factors including temperature and ionic strength on the gelation and hence the dissolution of amorphous LH.

METHODS

Dissolution tests of amorphous LH were performed under different temperatures and buffer ionic strengths. The formed gels were characterized by rheology study, texture analysis, PLM, SEM, DSC, XRPD and FTIR.

RESULTS

With the increase of temperature and ionic strength of medium, the dissolution of amorphous LH decreased, while the strength, hardness and adhesiveness of in situ formed gel enhanced. Amorphous LH converted into its crystalline state during dissolution and the crystallization rate was affected by medium conditions. With medium temperature increasing from 30°C to 45°C, the gel microstructure changed from interconnecting fibrillar network to spherical particle aggregate. On the other hand, the formed spherulitic gel aggregate exhibited increased particle size when increasing the ionic strength of medium.

CONCLUSIONS

With increase of temperature and ionic strength, the gel strength of in situ formed gel from amorphous LH enhanced with more compact microstructure, subsequently leading to decreased dissolution profiles.