ENHANCEMENT OF SOLUBILITY AND DISSOLUTION OF NIMESULIDE USING SOLUBILIZATION, SOLID DISPERSION AND COMPLEXATION TECHNIQUES

Nimesulide is a preferential COX-2 inhibitor. It has high anti-inflammatory, antipyretic and analgesic activities. It has poor aqueous solubility (0.01mg/ml). Solubility of nimesulide was studied using different cosolvent mixtures and various classes of nonionic surfactants. Dimethylacetamide (DMA); at 10% v/v exhibited the highest solubilizing effect (10-fold) towards nimesulide as compared with other cosolvents. Among the tested nonionic surfactants at 10% w/v, brij 58 which exhibited the highest solubilization effect (39-fold). The dissolution of nimesulide from solid dispersions was also studied. Solid inclusion complexes of nimesulide with β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP β-CD) were prepared at a molar ratio of 1:1. Eutectic mixtures were obtained at weight ratio of 1:9 binary systems as confirmed by DSC studies. The dissolution studies indicated that the highest relative amounts dissolved were obtained from solid dispersions as compared with physical mixtures or pure nimesulide. Also higher relative amounts dissolved were obtained with polyvinylpyrrolidones (PVPs) at weight ratio of nimesulide/PVP 40000 1:7. Physicochemical characterization of pure drug, PVP 40000, nimesulide/PVP 40000 solid dispersion and the physical mixture at this ratio were conducted by DSC, FTIR, X-RPD and SEM. The DSC thermograms and X-RPD patterns demonstrated that nimesulide existed in an amorphous form and there is an intermolecular hydrogen bond between the drug and the carrier as shown from FTIR analysis. SEM images confirmed the absence of the crystalline structure of nimesulide in the solid dispersion.