Cocrystal screening of anticancer drug p-toluenesulfonamide and preparation by supercritical antisolvent process

Abstract

p-Toluenesulfonamide (PTS) is a new anticancer drug in development. Its poor dissolution behavior complicates the design and development of the formulation process. The present study aimed to improve the dissolution profile of PTS by using a cocrystal engineering approach. Cocrystal screening of PTS with commonly used coformers was investigated, including 4,4′-bipyridine, nicotinamide, isonicotinamide, and sulfacetamide. According to the results of PXRD, FTIR, DSC, and elemental analyzer, a cocrystal of PTS with coformer 4,4′-bipyridine in a stoichiometric ratio of 2:1 was first disclosed. The single crystal of this cocrystal was then prepared, and the crystallographic data were identified and reported. In addition, an intensified crystallization technique, the supercritical antisolvent (SAS) process, was applied to produce this cocrystal using CO2 as the antisolvent. The effect of SAS process parameters was studied, including the operating temperature, operating pressure, solution flow rate, and nozzle diameter. Optimized SAS conditions were proposed for cocrystal preparation, yielding a total powder recovery of approximately 70% and a purity level of up to 90%. Furthermore, according to the results of the dissolution rate study, the dissolution rate of SAS-produced cocrystal was enhanced considerably about 375 times compared to the physical mixture.