Physicochemical and pharmacological properties of nimesulide/beta-cyclodextrin formulations

This study was carried out with the aim of optimizing the pharmacological p rofile of a non-steroidal anti-inflammatory drug, nimesulide, through the u se of solid systems containing beta-cyclodextrin. The interactions between nimesulide and beta-cyclodextrin were thoroughly investigated both in solut ion and in the solid state. The effect of beta-cyclodextrin on the aqueous solubility of nimesulide was evaluated using the phase solubility method. T he amount of nimesulide dissolved increased linearly with the addition of b eta-cyclodextrin according to an A(L) type plot and without precipitation o f the complex. The apparent stability constant of the complex, calculated u sing this method and supposing 1:1 stoichemetry, was 533 M-1; this was conf irmed by and UV spectrophotometry-based method. The increase in the apparen t hydrophilicity of nimesulide due to beta-cyclodextrin was confirmed by th e n-octanol/buffer partition coefficient of the drug, either alone or in th e presence of an equimolar amount of beta-cyclodextrin at PH values of 2.0, 4.5 and 7.4. Equimolar nimesulide/beta-cyclodextrin solid systems were pre pared using various techniques (physical mixing, kneading, co-evaporation, freeze-drying, spray-drying) and fully characterized by differential scanni ng calorimetry, X-ray powder diffractometry and Fourier transport infra-red analysis. This results of the solid state study demonstrated that freeze- and spray-dried products had the highest degree of amorphization and agreed with the hypothesis of the existence of an inclusion in the solid state. T he dissolution profile of the drug was affected by the physico-chemical pro perties of each solid state system, the freeze-dried and spray-dried produc ts being the most rapidly dissolving forms. The analgesic and ulcerogenic a ctivities of nimesulide/beta-cyclodextrin systems, determined after oral ad ministration in rats, have shown an improvement in the pharmacological prof ile of MlM with cyclodextin-containing systems.