Characterization of ternary solid dispersions of nimesulide with Inutec SP1 and β-cyclodextrin and evaluation of anti-inflammatory efficiency in rats

Abstract

Objective The objective of this investigation is to enhance the physicochemical properties of nimesulide (NS) and the stability of NS solid dispersions in order to improve the anti-inflammatory activity of the drug. Background NS – a NSAID – is sparingly soluble in water and this low aqueous solubility in addition to its poor wettability leads to variability in the bioavailability of the drug. Materials and methods In the present study, ternary dispersions of NS were investigated using a new polymeric carrier, Inutec SP1 (Inutec), in combination with β cyclodextrin (β-CD). The ternary dispersions were prepared using different ratios of NS and β-CD (2 : 1; 1 : 1; 1 : 2), to which a fixed amount of Inutec (20% w/w of total formula) was added using different methods of incorporation of the drug. Physical mixtures of equivalent compositions were prepared by physically mixing the ingredients. The optimal formulation obtained with a full factorial experimental design was used for the evaluation of anti-inflammatory activity. Results In the ternary dispersions, the dissolution behavior improved in comparison with the physical mixtures and was found to be dependent on the technique of incorporation of the drug, the method of preparation, and the molar ratio of drug to β-CD. Physical characterization of the ternary dispersions by infrared spectroscopy (FTIR), differential scanning calorimetry, and X-ray powder diffraction indicated a decrease in crystallinity because of partial inclusion in β-CD and the effect of Inutec, which promoted the formation of microcrystals or partial amorphization of the drug during the processing of the dispersions by kneading. Differential scanning calorimetry and X-ray powder diffraction curves of the dispersions prepared by the solvent method indicated the presence of a polymorphic form of NS with a lower melting point. The optimized ternary dispersion predicted by the full factorial design showed good physical stability following an accelerated stability test. The ternary dispersion of NS, Inutec, and β-CD was found to show better anti-inflammatory efficiency in rats compared with a commercial tablet of NS. Conclusion It can be concluded that the dissolution properties and the anti-inflammatory efficacy of the ternary dispersions of NS with β-CD and Inutec were enhanced because of a secondary solubilization of the inclusion by the polymeric surfactant.