Insight into inclusion complexation of indomethacin nicotinamide cocrystals

The objective of this research was to investigate the feasibility of the interaction between indomethacin-nicotinamide cocrystals with β-cyclodextrin and hydroxypropyl-β-cyclodextrin in the solid-state. The study has emphasized on the possibility of inclusion complex formation and its effect on the dissolution performance of the cocrystals. The solid systems in the molar ratio of 1:1 of the host and guest molecules were prepared by co-grinding and co-evaporation methods and compared with their physical mixtures. Furthermore, the molecular behaviors of the cocrystals in all prepared samples were thoroughly characterized by powder X-ray diffraction, differential scanning calorimetry, Fourier-transform infrared spectroscopy, scanning electron microscopy and in-vitro dissolution performance. The results of these studies indicated that complexes prepared by the co-evaporation method with hydroxypropyl-β-cyclodextrin have shown complete inclusion of the cocrystals into the cyclodextrin cavity and a partial inclusion with β-cyclodextrin. Moreover, a significant (p < 0.05; ANOVA/Tukey) higher in-vitro dissolution was achieved in co-evaporate complex prepared with hydroxypropyl-β-cyclodextrin compared to that prepared with β-cyclodextrin, indomethacin-nicotinamide cocrystals and indomethacin itself.