Pharmaceutical salts: A formulation trick or a clinical conundrum?

The term pharmaceutical salt is used to refer to an ionisable drug that has been combined with a counter-ion to form a neutral complex. Converting a drug into a salt through this process can increase its chemical stability, render the complex easier to administer and allow manipulation of the agent's pharmacokinetic profile. Salt selection is now a common standard operation performed with small ionisable molecules during drug development, and in many cases the drug salts display preferential properties as compared with the parent molecule. As a consequence, there has been a rapid increase in the number of drugs produced in salt form, so that today almost half of the clinically used drugs are salts. This, combined with the increase in generic drug production, means that many drugs are now produced in more than one salt form. In almost all cases where multiple drug salts of the same agent exist, they have been marketed as therapeutically equivalent and clinicians often treat the different salt forms identically. However, in many cases this may not be justified. This review describes why many pharmaceutical salts are, in fact, not chemically equivalent, and discusses whether such chemical differences may translate into differences in therapeutic effectiveness. It will also explore, with examples, what the clinical cardiologist should consider when prescribing such agents for their patients.