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  • Title: Development of a pharmaceutical cocrystal with solution crystallization technology: Preparation, characterization, and evaluation of myricetin-proline cocrystals.
    Author: Liu M, Hong C, Yao Y, Shen H, Ji G, Li G, Xie Y.
    Journal: Eur J Pharm Biopharm; 2016 Oct; 107():151-9. PubMed ID: 27395394.
    Abstract:
    Myricetin shows low oral bioavailability (<10%) in rats due to poor aqueous solubility, although it has demonstrated various pharmacological activities such as those related to anticancer, anti-diabetes, and hepatic protection. To overcome this issue, in this study, pharmaceutical cocrystals were designed to efficiently deliver myricetin by oral administration. A 1:2 stoichiometric cocrystal of myricetin with proline was prepared successfully by solution crystallization based on the ternary phase diagram (TPD) principle, and it is presented as a new sphericity-like crystalline phase characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The formation of myricetin-proline cocrystals was a spontaneous and exothermic process, probably due to the supramolecular interactions between themselves, which were determined by Fourier transform-infrared spectroscopy (FT-IR). Consequently, the dissolution efficiency of myricetin from cocrystals was increased 7.69-fold compared with that of coarse myricetin, and the oral bioavailability of myricetin cocrystals in rats was enhanced by approximately 3.03 times compared with that of pure myricetin. The present study provides useful information for the potential application of cocrystal technology for water-insoluble drugs, especially flavonoid compounds.
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