Comparative evaluation of ibuprofen co-crystals prepared by solvent evaporation and hot melt extrusion technology

Abstract

Ibuprofen (IBP) is a BCS Class – II drug that belongs to Non-Steroidal Anti-Inflammatory Drug (NSAID) category, having very poor solubility. In the present study, we have explored co-crystallization as a method of solubility enhancement of IBP. l-proline was selected as co-former based on its pKa difference with IBP, Hansen Solubility Parameter (HSP), and computational studies. The initial trials were taken using solvent evaporation method and later studied by hot melt extrusion technique to compare the results. The co-crystals were characterized by visual morphology, Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Fourier Transform-Infrared Spectroscopy (FT-IR), and Powder X-Ray Diffraction (PXRD) studies. The co-crystals were further evaluated for contact angle studies, solubility studies, dissolution studies, flow properties, and compressibility studies. Co-crystals showed distinct morphology in the SEM study compared to plain IBP. The DSC thermogram revealed a new melting endotherm of the co-crystals. Peak shifts and band broadening were also observed in FT-IR study indication formation co-crystals. The change in crystal lattice was confirmed using PXRD studies. In-vitro dissolution studies have shown higher drug release of co-crystals compared to physical mixture however the release differed in different media. No change in crystallinity of co-crystals was observed during compressibility studies. Thus, melt extrusion technique was successfully explored for IBP co-crystals using l-proline as the co-former.