Development of Ketoprofen-p-Aminobenzoic Acid Co-Crystal: Formulation, Characterization, Optimization and Evaluation

Abstract Co-crystal is a promising class of solids that may provide options for improved properties. In the present study, ketoprofen- p-aminobenzoic acid (KP-PABA) co-crystal were prepared to sought enhanced solubility and dissolution rate of drug. KP-PABA co-crystal were prepared by solvent evaporation technique employing central composite experimental design, selecting independent variables as concentration of drug and PABA whereas dependent variables were assumed to be solubility and % drug release. The optimized batch as suggested 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. Co-crystal containing ketoprofen and PABA in molar ratio (1:1) was found to be optimized formulation batch. Physical characterization by X-ray diffraction spectra and differential scanning calorimetric studies confirms the crystallinity of prepared co-crystal. The half maximal inhibitory concentration (IC50) values for in-vitro anti-inflammatory activity comes out to be 34.04 µM for ketoprofen and 4.373µM for optimized formulation, exhibiting almost 8-fold amplification indicating higher anti-inflammatory effect of optimized batch as compared to 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. In this case, a crystalline molecular complex of drug Ketoprofen, that demonstrate poor aqueous solubility, with p-aminobenzoic acid was recognized that further set out an improvement in solubility and also in anti-inflammatory activity of the drug in wistar rats.