Intensified Crystallization Processes for 1:1 Drug–Drug Cocrystals of Sulfathiazole–Theophylline, and Sulfathiazole–Sulfanilamide

Abstract

The chemical synthesis and crystallization steps were integrated successfully for directly producing a 1:1 cocrystal of sulfathiazole–theophylline and a 1:1 cocrystal of sulfathiazole–sulfanilamide. The benefits of this process intensification were the reduction of number of steps, and the amount of energy consumption and solvent used. In addition, the overall cocrystal yields by Intensified Method I were much higher than the ones by the conventional method. Intensified Method I also gave high-purity cocrystals of ≥99%. Sulfathiazole not forming cocrystals with sulfanilamide by Intensified Method I was dissolved in the mother liquor by taking advantage of the pH-dependent solubility of sulfathiazole. Cocrystals of both sulfathiazole–theophylline and sulfathiazole–sulfanilamide systems remained stable under conditions of 40 °C and 75% relative humidity for a month.