A factor analysis for complex systems containing nimesulide.

Abstract

Binary systems containing Nimesulide and PEG 4000 were prepared by the melting method in the concentration range 3-25% w/w of the drug. The systems are homogeneous in the molten state, while, after cooling, two phases were formed of different density. They were manually separated and separately studied. Upper phases are richer in PEG 4000, while the lower ones contain the drug at levels even higher than those of the starting mixtures. The two phases were examined by DSC and UV techniques; high dissolution rates were observed with upper phases, while lower phases did not display improvement with respect to a physical mixture or micronized drug. With the aim to avoid phase separation, a third component was added to the binary system containing 5% w/w drug, during the melting. The ternary systems were prepared containing sodium dodecyl sulfate, triethanolamine, polysorbate 80, poloxamer, and cetomacrogol: a homogeneous phase was obtained only in two cases (with the addition of sodium dodecyl sulfate and triethanolamine), but only in the presence of triethanolamine dissolution rate was improved. Finally, a factor analysis was performed for complex systems containing a combination of the four additives, each one at two concentrations (1.25 and 2.5% w/w), to evaluate the optimum system in terms of both kinetic and composition parameters. Results suggest that additives affect mainly the physical aspect of the formulation rather than the kinetic behavior, which appears little improved only in a few cases.