Drug Discov Ther. 2008;2(2):122-127.
Using factorial design to improve the solubility and in-vitro dissolution of nimesulide hydrophilic polymer binary systems.
Khattab IS, Al-Saidan SM, Nada AH, Zaghloul AA
The aim of the present study was to use factorial design to enhance the dissolution rate of nimesulide using solid binary systems with the hydrophilic carriers D-mannitol and polyethylene glycol (PEG 4000). Two-factor full factorial design was employed to investigate the effects of the drug/carrier ratio (X1, 10 and 20%) and the method of preparation (X2, physical or co-melted mixture) on the percent drug release after 60 min (Y1). Drugcarrier co-melted mixtures were prepared by melting the carriers D-mannitol or PEG with the drug. For physical mixtures, the drug and carrier were mixed thoroughly in a mortar until a homogeneous mixture was obtained. Drug-carrier interactions were investigated by differential scanning calorimetry (DSC). All prepared mixtures were filled in hard gelatin capsules, size 0, and then their dissolution rate was tested. The results showed an increase in the solubility of the drug with increasing polymer concentrations. Thermal analysis revealed no notable differences regarding thermal events of nimesulide, D-mannitol, PEG 4000, and their physical or comelted mixtures. The percent drug released after 60 min was 29.5% for nimesulide alone, 37.14 and 32.0% for a PEG/Physical mixture with a 10 or 20% drug/polymer ratio, and 69.7 and 53.1% for a PEG/Co-melted mixture with the same ratios. For nimesulide/D-mannitol, this percent drug released was 33.57 and 29.6% for a physical mixture and 63.13 and 48.04% for a co-melted mixture. Formulations with PEG showed an increase in solubility as well as dissolution in comparison to those prepared with D-mannitol. Factorial design was successfully used to optimize the dissolution rate of nimesulide. The chosen polymers caused a notable increase in drug solubility and co-melted formulations generally showed a higher dissolution than those prepared with physical mixtures.