Improvement of Nimesulide Dissolution by a Co‐grinding Method Using Surfactants

Abstract

A co-grinding method was used to improve the dissolution characteristics of nimesulide, a poorly water-soluble non-steroidal anti-inflammatory drug. Nimesulide solubility was studied to determine the solubilization process using different concentrations of Tween 80 at different pH values. At a 10% Tween 80 concentration, a large proportion (> 90%) of drug was entrapped in micelles when the pH of buffer solution was greater than pKa of nimesulide. A 32 factorial design was adopted using the concentration of Tween 80 and sodium lauryl sulphate as independent variables. Improved drug dissolution was obtained when the drug was mixed first with aqueous surfactant solution and later blended with adjuvant such as lactose and microcrystalline cellulose. Sodium lauryl sulphate was more effective in increasing the drug dissolution compared with Tween 80. The use of a blend of Tween 80 and sodium lauryl sulphate is justified since the interaction term (Tween 80 x sodium lauryl sulphate) for percentage drug release in 45 and 120 min was not significant. Contour plots were obtained for the angle of repose and percentage drug release in 30, 45 and 120 min. The study revealed that optimum level of surfactants should be used. The granule flow was adversely affected and no further improvement of drug dissolution was observed when the surfactants were used at high levels. The improved drug dissolution may be attributed to improved wetting and micellization due to presence of surfactants or hydrophilic adjuvant. More than two-fold increase in the drug dissolution was obtained by the selected batches.