The novel cocrystals of acacetin with 4,4′-bipyridine and 2,2′-bipyridine: Crystal structures analysis, stability and dissolution evaluation

To our best knowledge, acacetin has great potential for market development and clinical application due to its various pharmacological effects including antioxidant, anti-inflammatory, anti-cancer, neuroprotective, hepatoprotective, cardioprotective and so on. However, low solubility and poor bioavailability overshadow its prospect for new drug development and application. In order to optimize the solubility of acacetin, a scientific and reasonable cocrystal design was launched. In this study, the cocrystal of acacetin-4,4′-bipyridine and acacetin-2,2′-bipyridine were successfully prepared and systematically characterized by single-crystal X-ray diffraction, powder X-ray diffraction, fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. With the efforts of structural analysis and theoretical calculation, it was found that the two formed cocrystals including acacetin-4,4′-bipyridine and acacetin-2,2′-bipyridine possessed significant distinctions in terms of the type of space group and crystal system, the lattice arrangement as well as the forces and hydrogen bonds connections involved in the generation of cocrystals. By the evaluation of stability and dissolution, the results indicated that two cocrystals could keep stable under high temperature, high humidity as well as light condition and significant enhancement in the solubility and dissolution rate of acacetin were achieved by the formation of two new cocrystals which might be contributed to the increase of its bioavailability. This study was of significance to not only investigate the differences of two cocrystals in the aspects of space group, lattice arrangement, intermolecular force and thermodynamic stability, but also provided a new approach to optimize the solubility of acacetin.