Preparation,properties and bioavailability of drug-drug cocrystal of luteolin
Objective To synthesize luteolin-5-fluorouracil(LU-5-FU cocrystal)and luteolin-nicotinic acid(LU-NA cocrystal)cocrystals and improve their water solubility and bioavailability.Methods Two drug-drug cocrystals were designed and synthesized by wet grinding and solvent method.They were characterized by powder X-ray diffraction,infrared spectroscopy,differential thermal analysis and nuclear magnetic resonance spectroscopy.Their in vitro dissolution in pH 1.2 hydrochloric acid solution was determined by high performance liquid chromatography.The main pharmacokinetic parameters of rats were calculated.Results The characteristic spectra of LU-5-FU cocrystal and LU-NA cocrystal appeared.The maximum dissolution rate in the pH 1.2 hydrochloric acid solution increased by 2320％and 300％,respectively.In the pharmacokinetic experiments,there was a significant difference(P＜0.05)in the maximum blood drug concentration(Cmax)and area under the curve(AUC0～t)of LU-5-FU cocrystal and LU-NA cocrystal as compared with the raw material of luteolin.The Cmax and A UC0～t were greatly improved as compared with the raw material of luteolin,with relative bioavailability at 850％and 560％,respectively.Conclusion Two target cocrystals with a stoichiometric ratio of 1∶1 are synthesized,whose in vitro dissolution and in vivo bioavailability of luteolin have been improved.
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