Cocrystal solubility

Cocrystals have emerged as a promising means to modify solubility, dissolution and other physicochemical properties of drug substances.

Cocrystals are made of a drug and a coformer, which can be neutral or ionisable compounds. As solubility of cocrystals is related to the properties of the pure components, when drug, coformer or both (drug and coformer) are ionisable, solubility of the cocrystals will be pH dependent.

 Another important feature in solubility determination of cocrystals is that some of the most relevant pharmaceutical cocrystals are more soluble than the pure drug or coformer form. As a consequence, there is a solid phase transformation when exposed to solvent, i. e., the most insoluble component of the cocrystals (drug, coformer, or coformer salts) precipitates. Then, the achieved solubility value is the one of the most insoluble component instead of the solubility of cocrystal itself.

When this happens, the establishment of true cocrystal-solution equilibrium is not experimentally achievable, and solubility of the cocrystal must be estimated through the Ka of the components and the Ks of the cocrystal, which in turn must be experimentally determined under controlled conditions.

For further information, please Contact us.