Abstract
Luteolin is an important flavonoid with low water solubility and oral bioavailability properties, which limit its further clinical applications. In the present study, two new cocrystals of luteolin monohydrate with isoniazid and caffeine have been synthesized successfully using liquid assisted grinding method. Solid characterizations including X-ray diffraction, thermal and spectroscopic analysis were carefully performed to identify the two new cocrystals. Temperature-composition phase diagrams for both cocrystals were plotted through differential scanning calorimetry data. The maximum and minimum extreme values of all the compounds on molecular electrostatic potential surfaces that can be converted into hydrogen driving forces were calculated and illustrated. The luteolin-isoniazid cocrystal presents the solubility (112.3 μg mL−1) about three times better than luteolin monohydrate. In the pharmacokinetic analysis, the integrated AUC0-∞ of luteolin-isoniazid and luteolin-caffeine cocrystals performed 2.7 folds and 1.4 folds respectively more enhancements than luteolin monohydrate.
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