Modulation of biopharmaceutical properties of drugs using sulfonate counterions: A critical analysis of FDA-approved pharmaceutical salts

The physicochemical and ADMET properties of drugs can be modulated by converting them into a suitable salt form. The detailed analysis of the FDA database over the past 80-years revealed the contribution of 49-counterions in pharmaceutical salts with varying ionic charge, dissociation constant, and aqueous solubility. The ‘sulfonate’ is one of the key counterions comprising inorganic sulfate and organic sulfonates. Phentolamine mesylate is the first sulfonate salt approved in 1952 as an antihypertensive medication. So far, 69 sulfonate salts are approved by FDA in the last seven decades comprising sulfate, mesylate, besylate, tosylate, methylsulfate, camsylate, isethionate, and edisylate salts. Among these sulfonate salts, mesylate (25 drugs) and sulfate (24 drugs) have a major share. This review provides an account of FDA-approved sulfonate salts from 1952 to 2020. The decade-wise analysis indicates that 2011–2020 contributed a maximum number of sulfonate salts (19) and least (5) in 1971–1980. The technical advantage of sulfonate salts over other salt forms and the parent drug is also discussed.