Study of factors affecting the process of complexation of nimesulide - γ-cyclodextrin

Complexation helps to increase the solubility as well as improving other qualities of drug substances. To study this process and subsequent preparation of compounds, we chose γ-cyclodextrin and nimesulide, a widely used drug for the treatment of acute and chronic pain.

To obtain the inclusion complexes, we used a combination of methods: co-evaporation and coprecipitation. Varying some parameters of complexation (the pH of the reaction mixture (pH = 3; pH = 7), and the presence and volume of additional solvent (acetone)), several samples of putative complexes were obtained as a result of the experiment. Qualitative analysis was carried out by FTIR spectroscopy on a Fourier spectrometer (‘FMS 1201’, Russia). The obtained IR spectra suggest that some functional groups of nimesulide (S=O, R-NO2) interacting with functional groups of γ-CD lead to a shift in the corresponding absorption bands. The formation of the complex was further confirmed by differential scanning calorimetry. The change in the enthalpy of phase transition with respect to the pure substance indirectly testifies to the formation of the complex compound. The quantitative composition of inclusion complexes was studied using a calibration plot method on a Shimadsu UV-1800 UV spectrometer. Quantitative analysis showed that the most complete incorporation of nimesulide into the cavity of γ-CD is achieved with the addition of an additional solvent (acetone) and the observance of an acidic environment in the reaction mixture. A change in other parameters (temperature or time of mixing the reaction mixture) did not have a noticeable effect on the process. the toxicological activity of the obtained compounds was not studied. Based on the confirmed safety of nimesulide and γ-CD, we assume that the complexes are also non-toxic.

Thus, knowing the factors that have a predominant influence on the process of complexation, it is possible to obtain inclusion complexes of cyclodextrins with various drugs, creating new modified forms.