title: Development of a pharmaceutical cocrystal with solution crystallization technology: Preparation, characterization, and evaluation of myricetin-proline cocrystals.
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.
authors.affiliation: Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liu
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hong
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Yashu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Shen
authors.affiliation: Institute of Digestive Diseases, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.affiliation: Pharmacy Department, Shanghai TCM-integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China. Electronic address: lgwshutcm@163.com.
authors.forename: Guowen
authors.initials: G
authors.lastname: Li
authors.affiliation: Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Institute of Digestive Diseases, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: rosexie_1996@hotmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
mesh_terms: D003460:Crystallization; D005419:Flavonoids / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D033362:Powder Diffraction; D011392:Proline / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D005419:Flavonoids; D012996:Solutions; C040015:myricetin; D011392:Proline
keywords: 2,4-Dinitro-fluorobenzene (PubChem CID: 6264); Acetic acid (PubChem CID: 176); Acetonitrile (PubChem CID: 6342); Bioavailability; Cocrystal formation; Ethanol (PubChem CID: 702); Myricetin; Myricetin (PubChem CID: 5281672); N,N-dimethylformamide (PubChem CID: 6228); Potassium phosphate monobasic (PubChem CID: 516951); Proline; Proline (PubChem CID: 145742); Sodium acetate (PubChem CID: 517045); Sodium bicarbonate (PubChem CID: 516892); Solubility