Cocrystal Formers (CCF)

Preparative Strategy

Key Findings

References

Caffeine

Isonicotine

Nicotinamide

4-cyanopyridine

Solvent Crystallization

・ Studies have shown that the solubility increases by 3 to 80 times after the formation of the cocrystal, and the peak time is reduced to 10 to 20 minutes.

[29]

Proline

Solution Crystallization

・ The highest solubility of myricetin-proline cocrystal in 40 minutes is 7.69 times that of myricetin flavone and 2.83 times that of myricetin-proline physical mixture.

・ The blood concentration of myricetin in the cocrystal is about 3.45 times higher than that of pure myricetin.

[30]

4,4’-bipyridine

Solution Evaporation

・ This work successfully demonstrates that the stoichiometric ratio could be inferred by analysing the possible number of intermolecular hydrogen bonds between flavonoids and amines.

・ The results showed that the cocrystal compound has a broader antibacterial activity than a single myricetin.

[15]

API:

Dihydromyricetin

Solution Crystallization

・ This study demonstrates that the use of a highly soluble cocrystal along with an appropriate crystallization inhibitor is a potentially effective formulation strategy for improving oral bioavailability of poorly soluble BCS IV drugs.

[31]

CCF:

Caffeine; Urea

Berberine chloride

Solution Crystallization

・ The hydroxyl group of myricetin form O-H…Cl⁻ with chloride anions, and the intermolecular interactions dominate the formation of cocrystal.

・ Cocrystals revealed low moisture adsorption up to 95% of relative humidity and enhanced solubility in water.

[32]