Take It With a Grain of Salt

Salt is more than what you sprinkle on your popcorn! That white powder is referred to as "salt," but it is really just one salt in a class of compounds. A salt is a material that is made from the reaction of an acid and a base. Do you remember learning about acids and bases in school or helping a child with a homework experiment? Read on for a refresher on what they are, how they form salts, and how we use salts in pharmaceuticals!

Acid – a compound that can "donate" a proton (a hydrogen atom missing an electron). Examples are acetic acid (vinegar), citric acid (present in citrus fruits, used to make sour candy), hydrochloric acid (found in stomach acid), sulfuric acid (car battery, petroleum manufacturing).

Base – A compound that can "accept" a proton. Examples are sodium bicarbonate (baking soda), soap, ammonia, sodium hydroxide (drain cleaner), sodium hypochlorite (bleach).

One way to make a salt is to mix an acid and a base. As the acid gives up a proton, it becomes negatively charged. Conversely, when the base accepts the proton, it becomes positively charged. This results in two oppositely charged particles that are tightly attracted to each other, forming an ionic bond. The new molecule will have different solubility and melting points.

Why is this important? See the next page to read how we use salts in pharmaceuticals.

We measure acids and bases on a scale called pH (1 to 14). This is measured in an aqueous (water) solution of the compound. A low pH is acidic, and a high pH is basic. A pH of 7 is a neutral compound. See the chart below for the pH values of common items (values are approximate and depend on the concentration of the aqueous solution).

Examples of some common salts include:

Salts can be used in pharmaceuticals to alter properties of molecules. Molecules can be produced in different crystal forms. These different forms can impact purity and solubility of a molecule. Another way to do that is to make a salt of the molecule of interest. A salt of a molecule can have different chemical (stability and purity profiles) properties and physical properties (solubility) from the neutral molecule.

Salts of APIs can be more soluble than their neutral forms – this can lead to better bioavailability. Because salts also have different physical properties such as crystallinity, they may provide a form of an API that can be purified better during the crystallization process.

Salts can also change the melting point of a molecule. Salts typically melt at a higher temperature than the neutral molecule and can provide a solid API as the salt vs a liquid as the neutral molecule. An example is valproic acid, which is a liquid and is formulated as soft gelatin capsules or a syrup. Making the sodium salt provides a solid API which can be formulated into tablets.

Excipients are non-active ingredients in drug products. They are non-active as they do not treat or cure disease but are functional as they provide a matrix for the active ingredient and can impact the release of the API molecule in a tablet or stabilize an API molecule in a solid or liquid formulation. Many of these are used in the form of a salt.

Examples include: