Studies on spectral characterization and solubility of hydroxypropyl β-cyclodextrin/iloperidone binary and ternary complexes using different auxiliary agents

Abstract

The antipsychotic drug Iloperidone (ILO) suffers from drawbacks of low solubility and poor bioavailability. In order to overcome such problems, we proposed to prepare binary and ternary complexes using kneading method and further compared for their ability to improve the solubility of ILO. Based on preliminary studies and phase solubility diagram, 1:1 ratio of drug and Hydroxypropyl β-cyclodextrin (HPβCD) was selected. Tartaric acid (TA) and Kolliphor P-188 (KP) were selected as auxiliary agents (AAs) for ternary systems. Significant improvements in the stability constant and complexation efficiency were seen in the phase solubility studies for TA in comparison to KP. Complexation was studied using PXRD, DSC, FT-IR and NMR. Apparent changes in the crystallinity of ILO were observed from PXRD and DSC studies, suggesting formation of complexes. The interactions in the inclusion complexes were confirmed by FT-IR and 1HNMR. Saturation solubility and in vitro dissolution studies showed increase in the drug solubility and release from the complexes compared to the pure drug alone. These studies suggest some interaction between AAs, ILO and HPβCD in ternary complexes. Thus, the present study led to the conclusion that AAs positively enhance solubility of the drug ILO and consequently may improve bioavailability.