Effect of p-sulfonatocalix[4]resorcinarene (PSC[4]R) on the solubility and bioavailability of a poorly water soluble drug lamotrigine (LMN) and computational investigation

Abstract

As a part of our research investigations to unfold the chemistry of calixresorcinarene, we studied the formation of an inclusion complex with p-sulfonatocalix[4]resorcinarene (PSC[4]R) of a poorly water soluble drug lamotrigine (LMN). The complete complexation of the drug was achieved after 48 h of stirring with PSC[4]R in water and evaporation of the water to give a solid complex. The inclusion complex between PSC[4]R and LMN was studied by different analytical techniques including FT-IR, PXRD and UV-VIS spectroscopy. The complexation was determined by thermal analysis and a phase solubility study. The prepared complexes exhibited improved in vitro dissolution profile and decreased in vivo acute oral toxicity compared to the pure drug. The results of the phase solubility experiments are in good conformity to signify the formation of 1 : 1 PSC[4]R : LMN complexes. Computational studies were performed to understand the intermolecular association of this inclusion complex using docking and short dynamic simulations. The purpose of this study was to enhance solubility resulting in high dissolution rate and bioavailability of this essentially poorly water soluble drug LMN.