Phenazopyridine Cocrystal and Salts That Exhibit Enhanced Solubility and Stability

One phenazopyridine monohydrate (1·H2O), one cocrystal of phenazopyridine with phthalimide (2), and three salts of phenazopyridine with benzoic acid (3), 4-hydroxyphenylacetic acid (4), and scaaharin (5) were synthesized, and their structures were determined by single crystal X-ray diffraction. The results of dissolution experiments indicate that the solubility of phenazopyridine can be enhanced after the formations of cocrystal and salts, in which the apparent solubility value of 5is approximately 9 times as large as that of phenazopyridine in water, and the apparent solubility value of 4 is approximately 10 times as large as that of phenazopyridine hydrochloride (1·HCl) in 0.1 M HCl aqueous solution. The results of the stability study demonstrate that 2–5 are less hygroscopic than 1·H2O and 1·HCl at both 85% and 98% RH.