Influence of auxiliary agents on solubility and dissolution profile of repaglinide with hydroxypropyl-β-cyclodextrin: inclusion complex formation and its solid-state characterization

Abstract

Inclusion complexation of repaglinide (RPG) with hydroxypropyl-β-cyclodextrin (HPβCD) in presence and absence of auxiliary substances such as polyvinyl pyrrolidone-K30 (PVP) and l-arginine (ARG) was formulated in an attempt to improve its physicochemical properties by using three different techniques viz. physical mixing—by geometric mixing of individual components, kneading method—by incorporating binder solution in physical mixture and co-evaporation method—by using rotary evaporator. Phase solubility studies showed formation of complex in 1:1 M ratio with AL type of curve in presence and absence of both auxiliary substances. The rise in stability constant was observed in presence of auxiliary substances suggests positive effect on complex formation. As compared to the complexes with PVP, tremendous improvement in aqueous solubility of RPG in supramolecular inclusion complex with ARG was observed. The solid state characterization of inclusion complexes prepared by different methods were carried out by differential scanning calorimetry (DSC), powder X-ray diffraction (PX-RD), fourier transformation-infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and in vitro dissolution studies. Among all complexes, ternary complex with ARG prepared by co-evaporation method showed improvement in dissolution profile of RPG indicating complete amorphization and entrapment of pure drug in HPβCD which is evident by DSC and PX-RD. Investigation concludes that ARG and PVP can show synergistic effect in inclusion complex formation of RPG with HPβCD.