Lurasidone-β-cyclodextrin complexes: Physicochemical characterization and comparison of their antidepressant, antipsychotic activities against that of self microemulsifying formulation

Abstract

Lurasidone hydrochloride (LHD) is an atypical antipsychotic drug has poor aqueous solubility and low bioavailability (9–19%). This study describes effect of different methods of complex formation with β-cyclodextrin (BCD) on enhancement of dissolution and on antidepressant, antipsychotic effects of LHD. Other purpose of this study is to compare pharmacodynamic effects of complexes with that of self microemulsifying drug delivery system of LHD (SMEDDS).Inclusion complexes (IC) of LHD and BCD were prepared by physical mixing (PM), kneading (KN) and spray drying (SD) in a 1:1 M ratio. These complexes were characterized by different techniques. KN and SD showing enhancement in dissolution, were compared with SMEDDS using Forced swim test (FST) and Tail suspension test (TST) for antidepressant action and Paw test for antipsychotic activity.Characterization of complexes confirmed interaction between LHD and BCD. Enhancement in dissolution is seen in following order SD > KN > PM > LHD. In all three animal models, SD, KN and SMEDDS showed statistically significant effect (p < .05) than drug alone showing enhancement in bioavailability.Complexation of LHD with BCD enhances dissolution which reflected in improvement of antidepressant and antipsychotic activity of drug. Solubility enhancement methods like complexation and self microemulsion improves pharmacodynamic activities of drug. Improvement of pharmacodynamic effect is seen in order, SD ≥ SMEDDS ≥ KN > LHD.