Dissolution behavior and thermodynamic stability of fused-sugar dispersions of a poorly water-soluble drug

Abstract

The current research was undertaken to develop and evaluate dissolution profiles of thermodynamically stabilized sugar dispersions of the poorly water-soluble, model drug etoricoxib (ETX). Fused-sugar dispersions were formulated using sorbitol, xylitol, and maltose separately, and the binary systems were stabilized by incorporation of the antiplasticizing agents poloxamer 407 and PVP K30 to obtain ternary and quaternary systems. The sugar dispersions (F1-F12) were subjected to in vitro dissolution studies, and based on model-independent dissolution parameters, ETX-sorbitol binary/ ternary/composite systems were selected for thermodynamic stability study. The aged ETX-sorbitol composite dispersion (SF8) displayed the highest percent dissolution efficiency (%DE80min of 78.48), the minimum t50% of 4.45 min, and the least tendency to recrystallize (Dcryst of 0.68), confirming maximum amorphization and thermodynamic stability among all the composite dispersions. The SEM photomicrographs reveal complete miscibility of drug in the aged quaternary dispersion SF8, and its diffuse reflectance (DR) spectrum confirms the absence of any chemical change. Conclusively, sorbitol binary systems can be effectively stabilized by incorporation of PVP K30-poloxamer 407 and retain the dissolution characteristics of sugar dispersions upon aging.