Salts of rucaparib with dicarboxylic acids: synthesis, crystal structures and solubility

Abstract

Rucaparib (RUC) is a potent poly (ADP-ribose) polymerase inhibitor for the treatment of advanced ovarian cancer and recurrent epithelial ovarian cancer. It is marketed in the form of its camsylate salt with a solubility of 1.4 nmol L⁻¹ and absolute oral bioavailability of 36–37%. To expand the solid-state scope of RUC, three salts with fumaric acid (RUC/FA, 2 : 1), adipic acid (RUC/AA, 1 : 1) and pimelic acid (RUC/PA, 1 : 1) were synthesized and characterized. The crystal structure and infrared spectroscopy analyses demonstrate that proton transfer occurs between the RUC and FA/AA/PA molecules, confirming the formation of salts. In comparison with the commercial camsylate salt of RUC, RUC/AA and RUC/PA exhibit significantly enhanced solubility without sacrificing hygroscopicity and physical stability. Therefore, RUC/AA and RUC/PA may have the potential for developing improved formulations of RUC.