API Salt Selection: A Classical but Evolving Approach in Modern Drug Development

For several decades, generating salt forms of the active pharmaceutical ingredients (APIs) has remained the preferred approach for the pharmaceutical industries. The salt form of the APIs provides the advantage of improving the solubility and stability, enhancing the dissolution rate, permeability, manufacturing robustness, taste masking, and life cycle management. The pharmaceutical salts are the ionic compounds of a drug and its counterion. The counterions can be classified as anionic, cationic, organic anions, and aromatic sulfonates. The salt form of the drug does not exhibit pH-dependent solubility. Developing a salt form of the drug will improve the bioavailability of poorly soluble drugs belonging to the biopharmaceutical classification system (BCS) class II and IV. Around 50% of the solid oral dosage forms in the market utilize the salt form of the drug. Identifying the suitable salt form right in the early stages of development will eliminate the need for complex formulation platforms such as amorphous solid dispersions. Despite various advantages, a few limitations must be addressed, such as hygroscopicity, polymorphism, and counterions. The salt screening can be integrated with artificial intelligence (AI) and computational tools to accelerate development. The review article summarizes the principles, benefits, limitations, and future outlook for pharmaceutical salts.