Facile syntheses of novel salts of a triazole antifungal agent with enhanced solubility

Abstract

Acid addition salts of a triazole antifungal agent itraconazole were prepared with an aim to enhance the aqueous solubility and dissolution characteristics of the drug. Nitric, sulfuric, and p-toluenesulfonic acid addition salts (1a-c) were prepared using facile synthetic procedures. The solubility of the salts in water was found to be 24, 22, and 58 mg/mL, respectively, for 1a, 1b, and 1c, which is significantly higher than that of itraconazole (1 ng/mL). In addition to this, solubility of the salts in simulated gastric fluid (SGF) and other pharmaceutically used solvents such as ethanol and propylene glycol was also improved to a great extent. Also, it was observed that from 1a, 1b, and 1c, approximately 33, 26, and 45% drug was released in SGF in 3 h, whereas less than 10% drug was released from the free base form. © 2013 HeteroCorporation.