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

Salification has a successful track record in modulating the biopharmaceutical properties of drugs. This is evident from the significant share (40%) of pharmaceutical salts in FDA-approved drugs in the past 80-years. Based on the ionic nature of drugs, the corresponding cationic or anionic counterions are employed for salification. This review aims to provide the contribution of cationic counterions in FDA-approved drugs from 1939 to 2020. The analysis of 80-years data has shown that the 7.1% of the FDA-approved drugs comprise cationic counterions (98 pharmaceutical salts). Heparin sodium is the pioneering drug in the history of pharmaceutical salts that was approved in 1939 as an anticoagulant medication. Inorganic (sodium, calcium, potassium, magnesium, silver), as well as organic (tromethamine, meglumine, erbumine) cationic counterions, were used in FDA-approved drugs with a major share by sodium (76 drugs). The technical superiority of cationic salts over other salt forms and the parent drug is also exemplified using case studies.