Polymorphic Ammonium Salts of the Antibiotic 4-Aminosalicylic Acid

Abstract

Reaction of the antibiotic 4-aminosalicylic acid with ammonia yields three polymorphic forms of the ammonium 4-aminosalicylate salt [NH4][C6H3NH2OH(COO)]. When the reaction is conducted in solution, the three polymorphs are obtained concomitantly, while liquid-assisted grinding and solid–gas reaction result in the formation of pure Form II. The three polymorphs are characterized by different patterns of hydrogen bonding interactions between the structurally rigid anions and the ammonium cations. Solid products were characterized by single-crystal and powder X-ray diffraction, variable temperature powder diffraction, calorimetric techniques (DSC and TGA), and hot-stage microscopy (HSM).