Improved oral absorption of (−)‐epigallocatechin‐3‐gallate via self‐double‐emulsifying solid formulation

Abstract

(−)‐Epigallocatechin‐3‐gallate (EGCG), the main active ingredient from the green tea leaves (Camelia sinensis L.), is a hydrophilic drug with low‐oral bioavailability (BCS class III). A novel self‐double‐emulsifying drug delivery system (SDEDDS) in solid form was formulated to improve the oral absorption of EGCG. Solubility of EGCG was determined in various components including water, oils, and surfactants. Pseudo‐ternary phase diagrams were constructed to identify the most efficient self‐emulsification region. The EGCG‐SDEDDS in solid formulation rapidly formed fine water‐in‐oil‐in‐water emulsion. Furthermore, in vitro cellular experiments have shown increase in the cellular uptake of EGCG incorporated in SDEDDS compared to pure drug, and in an in vivo pharmacokinetic study in rats, the SDEDDS formulation exhibited 1.93‐fold greater area‐under‐curve value than that of the drug solution. Stability studies have shown that solid EGCG‐SDEDDS was stable up to 6 months under intermediate condition. These studies demonstrated that the novel SDEDDS in solid form could be a promising formulation strategy for the drug delivery of hydrophilic compounds with low‐oral bioavailability.Practical applications: Solid SDEDDS could be used as a drug delivery system to encapsulate hydrophilic drug with low‐oral bioavailability. In vitro and in vivo experiments have shown increase uptake of EGCG incorporated in solid SDEDDS compared to pure drug. Solid SDEDDS also improved the storage stability of EGCG. Furthermore, the production procedure of SDEDDS is two‐step method, which is widespread and easy to handle. In regard to industrial production aspects, solid SDEDDS have the chance to be exploited as drug delivery system in commercial products. Hence, solid SDEDDS could be applicable delivery system for hydrophilic compounds with low‐oral bioavailability.A novel self‐double‐emulsifying drug delivery system (SDEDDS) in solid form is prepared by the modified two‐step method. The system can spontaneously emulsify into w/o/w double emulsions in the aqueous media. Pharmacokinetic studies reveal that solid SDEDDS shows 1.93‐fold absorption of EGCG compared to EGCG solution.