Formulation, Optimization, in Vitro and in Vivo Investigation of Ketoprofen - Fumaric Acid Co-crystal for the Solubility Enhancement of Ketoprofen

Abstract

The present piece of research work is framed as improving the solubility of ketoprofen by forming co-crystal using fumaric acid as a coformer. Co-crystal of ketoprofen and fumaric acid were prepared by simple solvent assisted grinding. The independent variables i.e. drug and coformer were mixed in 1:1 molar ratio and dependent variables were assumed to be solubility and % drug release. Differential scanning calorimetry, fourier transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance and scanning electron microscopy techniques were used to characterize the preparation of optimized batch of co-crystal and further, evaluated for in-vitro and in-vivo anti-inflammatory and analgesic activities. Based on results of solubility and dissolution rate studies the drug showed 4-5 fold improvement in both the properties on co-crystallisation. The values of Gibbs free energy are negative at all levels of carrier demonstrating spontaneity of drug solubilization process. The IC50 value of optimized batch of co-crystal formulation and pure drug was observed as 327.33 µg/ml and 556.11 µg/ml, respectively, demonstrating that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. In-vivo (anti-inflammatory and analgesic) activities revealed that optimized batch of co-crystal formulation delivered a rapid pharmacological response in wistar rats and albino mice when compared with standard drug.