Improving solubility of fisetin by cocrystallization
Fisetin, a naturally occurring polyphenolic compound, has a proven record of in vitro demonstrated anti-carcinogenic, anti-inflammatory and antiviral properties, yet similarly to many promising APIs, its in vivo administration is complicated by low aqueous solubility and unfavourable pharmacokinetics. The presented study was focused on obtaining and characterizing cocrystals of fisetin, with the aim of improving its solubility. Solvent-drop grinding experiments, combined with FT-Raman and XRPD, were conducted to identify new cocrystalline phases, which were afterwards isolated as single-crystals and characterized structurally and in terms of thermal stability and solubility. Dissolution studies of pure fisetin and four cocrystals, namely fisetin–isonicotinamide 1 : 1 (FisInam), fisetin–nicotinamide 1 : 2 hemiethanolate (FisNam), fisetin–nicotinamide 1 : 1 (FisNam2) and fisetin–caffeine 1 : 2 (FisCaf), showed that a 2.5-fold increase of fisetin solubility was achieved for FisNam and to a smaller extent for FisCaf and FisInam (ca. 1.8- and 1.5-fold, respectively).