Miscibility evaluation of Efavirenz and polymers for solid solution preparation by hot melt extrusion

Abstract

The aim of the present study was to evaluate the miscibility between efavirenz and various polymers (polyvinylcaprolactam-polyvinylacetate-polyethylene glycol graft copolymer (Soluplus®), vinylpyrrolidone-vinylacetate copolymers (Kollidon® VA-64), poly(butylmethacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methylmethacrylate) (Eudragit® EPO), polyvinylpyrrolidone (Kollidon® K-30), polyvinyl alcohol (PVA) and hydroxypropyl cellulose (HPC) for the preparation of solid solution by hot-melt extrusion process. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier-transform infrared spectroscopy (FT-IR) and dissolution test. Solid state moisture stability of extrudates was investigated by dynamic vapour sorption technique. The calculated solubility parameters showed that efavirenz were miscible with the polymers studied, except for HPC and PVA. Extrudates containing 50:50 efavirenz/polymer could be prepared by hot melt extrusion at 20 ºC above glass transition temperature (Tg) of each polymer. However, PVA mixture was not possible to be extruded. The extrudates, except for HPC, were found to be in solid solution form according to their transparent appearance. DSC thermograms showed absence of melting endotherm of efavirenz and presence of only single Tg. The XRPD patterns of the extrudates also showed absence of drug crystals. FT-IR spectra suggested possible interactions between efavirenz and polymers. Dissolution of efavirenz from the extrudates was markedly improved, as compared to the drug itself. In addition, the extrudates were stable after exposure to moisture sorption/desorption cycles as their amorphous character and dissolution behavior were marginally changed. Therefore, efavirenz and the polymers studied, except for HPC, were miscible and their solid solutions could be prepared by hot-melt extrusion process.