Preparation and Characterization of Cyclodextrin Inclusion Complexes for Improving Solubility and Dissolution of Nimesulide

Abstract

Nimesulide (4'-nitro-2'-phenoxy methane sulfonanilide) is a selective cyclooxygenase-2 inhibitor and one of the potent non steroidal anti-inflammatory drugs (NSAIDs). It is practically insoluble in water and hence has a low bioavailability. To improve solubility and dissolution of nimesulide, its β-cyclodextrin complex were prepared.

Nimesulide was complexed with β-cyclodextrin in 1:1, 1:2 and 1:3 molar ratios using solvent evaporation method with the addition of freeze drying. The prepared inclusion complexes were evaluated for solubility, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X ray powder diffraction (XRPD) and in vitro dissolution study. All the complexes showed about up to 12 fold increase in solubility.  The complex prepared in 1:3 ratios showed the greatest improvement in solubility (from 9.67 to 108.60 μg/ml). In SEM, the complexes showed irregular disc shaped non-porous surface. XRPD data indicated that maximum amorphization was induced in the complex prepared with 1:2 ratio. The DSC data confirmed the formation of inclusion complex. The dissolution of the drug in the complexes was also found to be improved. Complex prepared by solvent evaporation method in 1:2 molar ratio showed a marked improvement in dissolution profile (complete release in just 30 minutes) than that of pure drug which showed just 60.02 % drug release at the end of 3 hour.  It was concluded that the β-cyclodextrin complex made in 1:2 molar ratio showed good solubility and the dissolution profile as compared to the complex made in 1:1 and 1:3 molar ratio. It was concluded that the complex prepared by solvent evaporation method with 1:2 molar ratio showed the best performance with respect to great improvement in solubility, the best amorphization and the best in vitro dissolution profile as compared to other complexes.