Development of ketoprofen-p-aminobenzoic acid co-crystal: formulation, characterization, optimization, and evaluation

In the present study, ketoprofen- p- aminobenzoic acid (KP-PABA) co-crystal was prepared, to advance solubility and dissolution rate of drug, by solvent evaporation technique employing central composite experimental design. The optimized batch as recommended by the experimental design was characterized by FTIR, DSC, XRD, SEM, and NMR studies and further, evaluated for in-vitro and in-vivo anti-inflammatory and analgesic activities. The solubility and % drug release of different batches of co-crystal was found to be between 34.20–60.11 µg/ml and 68.11–93.45%, respectively. Physical characterization by X-ray diffraction spectra and differential scanning calorimetric studies confirmed the crystallinity of prepared co-crystal. The IC 50 value of optimized batch of co-crystal formulation and pure drug was observed as 248.79 µg/ml and 524.40 µg/ml, respectively, displaying that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. The results of in-vivo anti-inflammatory activity carried out by rat paw edema method revealed that the optimized batch of co-crystal preparation provided a significant % inhibition in paw volume in contrast to standard drug in wistar rats. Hence, the crystalline molecular complex of ketoprofen with p- aminobenzoic acid was documented that set out an improvement in solubility and also in anti-inflammatory activity of the drug in wistar rats.