free base

Many drugs contain a basic nitrogen atom that can grab a proton and become positively charged. When that nitrogen has not grabbed a proton — when the molecule is neutral and uncharged — the drug is in its free base form. It is the molecule in its naked, un-ionized state, before any acid has been added to make a salt.

The free base and the salt are two forms of the same active molecule. The free base is typically more lipophilic and far less water-soluble than the salt, because the charged, salt form interacts much more strongly with water. For this reason most basic drugs are developed and sold as salts to improve dissolution, while the free base is often an oily or low-melting solid that is harder to purify and handle.

Whether a basic drug exists as free base or as its protonated, charged form at any moment depends on the surrounding pH relative to the molecule's pKa. This matters biologically because only the uncharged free base readily crosses fatty cell membranes, while the charged form stays in water; the constant shifting between the two as a drug moves through the acidic stomach, the neutral intestine, and the blood shapes its absorption and distribution.