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

• Published in: CrystEngComm Vol. 24; no. 44; pp. 7813 - 782
• Main Authors: Wu, Chao, Gao, Lu, Xiong, Jing, Dai, Xia-Lin, Gao, Wei, Lu, Tong-Bu, Chen, Jia-Mei
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 14.11.2022
• Subjects: Bioavailability; Cancer; Crystal structure; Dicarboxylic acids; Fumaric acid; Hygroscopicity; Infrared analysis; Ribose; Solubility
• DOI: 10.1039/d2ce00842d
• ISSN: 1466-8033

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. Three new salts of rucaparib with fumaric acid, adipic acid and pimelic acid were synthesized and characterized, and the latter two demonstrate significantly improved solubility without sacrificing hygroscopicity and physical stability.