Enhancing Aqueous Solubility of Ketoprofen by Fusion Technique Using Suitable Co-formers

The aim of the present work was to prepare, characterize and evaluate the solubility and dissolution behavior of ketoprofen co-crystals. Fusion method was employed for the preparation of ketoprofen co-crystals. The co-formers selected were cinnamic acid, glutaric acid, maleic acid, malonic acid, nicotinamide, oxalic acid, p-amino-benzoic acid, pamino salicylic acid, saccharin and urea. The prepared ketoprofen co-crystals were characterized by FT-IR, DSC and XRD. Ketoprofen co-crystals were evaluated for solubility and dissolution. Micromeritic properties were evaluated for cocrystal exhibiting higher solubility. A Shift in the IR peaks was observed for all the prepared co-crystals with no presence of additional peaks. DSC studies showed decrease in the heat of fusion from 257.74 to 50.39 J/g and melting point of drug from 95.80 to 73.57°C in the co-crystals. XRD peaks exhibited different peak patterns than peaks shown by the pure ketoprofen. All the preparations exhibited enhanced aqueous solubility as well as dissolution when compared with pure ketoprofen. Amongst the co-crystals prepared, Ketoprofen-p-Amino-salicylic acid co-crystals, exhibited 14 fold increases in aqueous solubility and in vitro release was found to be 93.41% in 60 mins. This work demonstrates the potential of cocrystallization by fusion as screening method for particle engineering. The results demonstrate the feasibility of pharmaceutical co-crystal design for ketoprofen.