title: Crystal engineering of green tea epigallocatechin-3-gallate (EGCg) cocrystals and pharmacokinetic modulation in rats.
abstract: The most abundant polyphenol in green tea, epigallocatechin-3-gallate (EGCg), has recently received considerable attention due to the discovery of numerous health-promoting bioactivities. Despite reports of its poor oral bioavailability, EGCg has been included in many dietary supplement formulations. Conventional preformulation methods have been employed to improve the bioavailability of EGCg. However, these methods have limitations that hinder the development of EGCg as an effective therapeutic agent. In this study, we have utilized the basic concepts of crystal engineering and several crystallization techniques to screen for various solid crystalline forms of EGCg and evaluated the efficacy of crystal engineering for modulating the pharmacokinetics of EGCg. We synthesized and characterized seven previously undescribed crystal forms of EGCg including the pure crystal structure of EGCg. The aqueous solubility profiles of four new EGCg cocrystals were determined. These cocrystals were subsequently dosed at 100 mg EGCg per kg body weight in rats, and the plasma levels were monitored over the course of eight hours following the single oral dose. Two of the EGCg cocrystals were found to exhibit modest improvements in relative bioavailability. Further, cocrystallization resulted in marked effects on pharmacokinetic parameters including Cmax, Tmax, area under curve, relative bioavailability, and apparent terminal half-life. Our findings suggest that modulation of the pharmacokinetic profile of EGCg is possible using cocrystallization and that it offers certain opportunities that could be useful during its development as a therapeutic agent.
authors.affiliation: Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, USF Health College of Medicine, University of South Florida , Tampa, Florida 33612, United States.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Padmini
authors.initials: P
authors.lastname: Kavuru
authors.forename: Kapildev K
authors.initials: KK
authors.lastname: Arora
authors.forename: Sheshanka
authors.initials: S
authors.lastname: Kesani
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zaworotko
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Shytle
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013662:Tea / Q000737:chemistry*; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate