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 5 is 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.