Acta Pharm. 52 (2002) 227-241
The objective of the present investigation was to study the influence of croscarmellose sodium and Aerosil 200 as adsorbate carriers on in vitro dissolution of nimesulide from solid dispersion systems. Preliminary studies were carried out using the physical blends of nimesulide and adjuvants. Solid dispersions were prepared using solvent evaporation and co-grinding methods.
A 32 factorial design was adopted in the co-grinding method using the concentration of croscarmellose sodium and Aerosil 200 as independent variables. Tween 80, sodium lauryl sulphate (SLS), polyethylene glycol 400 (PEG 400), propylene glycol (PG) and polyvinylpyrrolidone K30 (PVPK30) were used in batches of factorial design. Full and reduced models were evolved for dependent variables, such as the angle of repose, percentage of drug release in 20 min (Q20) and percentage of drug release in 30 min (Q30). The reduced models were validated using two check-points. Angle of repose < 30°, Q20 > 75% and Q30 > 85% were used as constraints for the selection of an optimized batch. Contour plots are presented for the selected dependent variables.
Aerosil 200 was found to be more effective in increasing the drug dissolution compared to croscarmellose sodium. Wettability study was carried out for the pure drug and the optimized batch. Differential scanning calorimetry and X-ray diffraction studies were carried out in order to characterize the drug. Improved drug dissolution was attributed to decreased crystallinity of the drug, improved wetting and the solubilizing effect of adjuvants such as Tween 80, SLS, PEG 400, PG and PVP K30 from the solid dispersions of nimesulide. In conclusion, dissolution of nimesulide can be modulated using appropriate levels of functional pharmaceutical adjuvants.
Keywords: nimesulide, in vitro drug dissolution, solid dispersions, croscarmellose sodium, Aerosil 200, factorial design