Polymer solid dispersion system of nimesulide: in vitro dissolution assessment, thermodynamic and physicochemical characteristics

Nimesulide is a well-known non-steroidal anti-inflammatory active pharmaceutical ingredient (API), but it is poorly soluble in water, which makes its bioavailability relatively low. The aim of the work was to investigate the effect of polyvinylpyrrolidone (PVP) of different molecular weights on the phase solubility of nimesulide and to evaluate the thermodynamic parameters of the obtained complexes in order to determine the optimal polymer for further development of a solid dispersed system (SDS) of nimesulide and to study its physicochemical properties, which lead to an improvement in the solubility of API in the composition of the obtained composite material. Materials and methods. The dependence of the nimesulide dissolution profile in water on the concentration of PVP of different molecular weights was studied by the Higuchi and Connors method. SDS was prepared by the «green» method of solvent evaporation and were characterised by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) and were evaluated for dissolution profiles. Research results. The influence of PVP of different molecular weights on the phase solubility of nimesulide was studied, and it was found that the best increase in solubility in water was observed in the system with PVP K-25 – 5.27 times. Thermodynamic parameters of this composition were also investigated. The FTIR results indicate that the formation of complexes between the API and the polymer is predominantly due to hydrogen bonds. DSC and PXRD showed that nimesulide is present in SDS in an amorphous form. The results of the in vitro release kinetics study showed that the release rate of nimesulide from the formed SDS was higher than the dissolution rate of the comparison drug. Conclusions. A solid dispersed system prepared by the «green» method of solvent evaporation using PVP K-25 as a carrier can be used as a good strategy for formulating effective anti-inflammatory drugs of nimesulide with increased bioavailability