Identification, Isolation and Origin of Potential Dimer Impurities of Dichlorphenamide: A Carbonic Anhydrase Inhibitor Drug (Antiglaucoma)

Abstract

Present work describes the identification, isolation and characterization of two new process related dimeric impurities of dichlorphenamide (1). During the synthesis of dichlorphenamide, the formation of two new dimeric impurities namely 2,3-dichloro-5-(3,4-dichloro-5-sulfamoyl-phenyl)sulfonyl-benzenesulfonamide (2) (1,1′-dichlorphenamide dimer) and 2,3-dichloro-5-(2,3-dichloro-5-sulfamoyl-phenyl)sulfonyl-benzenesulfonamide (3) (1,3′-dichlorphenamide dimer) was observed. In addition, origin and the strategies adapted to control these potential dimer impurities were also described. These impurities have a substantial impact on the quality of the drug substance as well as drug product.