Novel Salts of the Atypical Antipsychotic Drug Lurasidone with Improved Solubility and Bioavailability

Lurasidone is an atypical antipsychotic drug for treating schizophrenia and bipolar disorder. The commercial form of lurasidone hydrochloride performs poor bioavailability and significant food effect owing to its poor water solubility. In this study, three novel salts of lurasidone, namely, lurasidone–ketoglutaric acid (LUD–KTA), lurasidone–trans-aconitic acid (LUD–TAA), and lurasidone–maleic acid (LUD–MA–H2O), were obtained and characterized by powder X-ray diffraction and thermal analyses. The molecular components and structures were confirmed by single-crystal X-ray diffraction. The results of the stability experiment showed that LUD–KTA and LUD–TAA exhibited satisfying physical stabilities. Based on in vitro powder dissolution experiments, the new salts achieved remarkably higher solubility than LUD-HCl. In addition, in vivo studies also showed that LUD–KTA and LUD–TAA provided superior bioavailability.