Cocrystals of betulin with adipic acid: preparation and thermal behavior

The cocrystal of betulin (BE) with adipic acid (AA) was prepared using a liquid-assisted grinding method. The formation of BE-AA cocrystal was confirmed by powder X-ray diffraction, IR spectroscopy and thermal analysis methods. It was assumed that 1:1 BE-AA cocrystal hydrate was formed when liquid-assisted grinding was carried out using water-miscible liquids in which the solubility of adipic acid was higher than in others. The cocrystal hydrate was stable under room temperature and rather high relative humidity. Nevertheless, the betulin–adipic acid cocrystal was found to decompose under heating after the loss of water molecules, followed by phase transformation. An anhydrous BE-AA cocrystal was also prepared by the BE-AA physical mixture heating up to the point of adipic acid melting.