Cocrystal Formers (CCF)

Preparative Stratagy

Key Findings

References

Isonicotinamide

Suspension Crystallization

(molar ratio 1:2)

・ Obtained a naringenin-isonicotinamide cocrystal

・ The dissolution behavior of the cocrystal has a significant advantage over naringenin and its physical mixture.

[20]

Nicotinamide

Isonicotinamide

Caffeine

Betaine

L-proline

Solution Crystallization

・ the C_max of naringenin-L-proline and naringenin-betaine cocrystal were 2.00 times and 3.35 times higher than that of pure naringenin

・ the AUC of naringenin-L-proline and naringenin-betaine cocrystal were 2.39 times and 4.91 times higher than that of pure naringenin

[21]

Piperazine salt

Flavone

4-hydroxypyridine

Anthranilamide

4,4’-bipyridine

Solution Crystallization

(molar ratio 1:1)

・ The four neutral cocrystals maintain the S(6) O-H・・・O = C intramolecular hydrogen bond seen in naringenin, and the carbonyl oxygen atom is bifurcated.

・ Solubility studies have shown that the formation of salt significantly increases the solubility of naringenin.

[22]

Carbamazepine

Solvent Slow Evaporation

・ The results present that polyhydroxyl groups with the structural features are effective to form typical intermolecular amino ・・・ hydroxyl interactions.

・ CBZ-NRG cocrystal affects the in vitro/vivo performance of CBZ significantly (Table 3), demonstrating lower dissolution with longer half-time life.

[23]

Carbamazepine

Drowning-out Crystallization

・ Naringenin (N) and carbamazepine (CBZ) cocrystallized at a stoichiometric ratio of 1:1 via strong interactions between the resorcinol groups of N and the urea groups of CBZ.

[24]