Choosing a salt
When the free acid or base of a drug is poorly soluble, awkward to crystallize, or unstable, the most common rescue is to make a salt. [[phc-salt-selection|Salt selection]] is the structured search for the best counter-ion: pair an acidic drug with a base (sodium, potassium) or a basic drug with an acid (hydrochloride, sulfate, tartrate), and you produce a new crystalline solid. The drug molecule is unchanged, but its salt can have dramatically better solubility, faster dissolution, a more convenient melting point, and better handling.
- Confirm the drug is ionizable. Salt formation needs an acidic or basic group; a neutral molecule has nothing to pair with — there a cocrystal may be the alternative.
- Make several candidate salts with pharmaceutically acceptable counter-ions and crystallize each.
- Characterize each — solubility, melting point, hygroscopicity, crystallinity, and solid-state stability.
- Pick the all-rounder, not the single best on one axis — a slightly less soluble salt that is stable and non-hygroscopic often wins.
Melting point: a quick, telling number
The melting point is the temperature at which the orderly crystal lattice collapses into a liquid. It is cheap to measure — often by differential scanning calorimetry on a milligram — yet it tells you a lot. A sharp, single melt suggests a pure, single crystalline form. A high melting point usually signals strong lattice forces, which often (not always) means lower solubility and good thermal stability. A low or smeared melt can warn of impurities, a mixture of forms, or a tendency to soften during processing.
Hygroscopicity: the thirsty powder problem
Some powders quietly drink water straight from the air. [[phc-hygroscopicity|Hygroscopicity]] measures that thirst — how much moisture a solid takes up as humidity rises. A little is normal; a lot is trouble. Absorbed water can cake a free-flowing powder into a brick, throw off the weighed amount of drug per dose, accelerate hydrolysis and other degradation, and even convert one solid form into a hydrate. A strongly hygroscopic salt may need a sealed container and humidity-controlled manufacturing rooms — real cost.