Development of a topical epigallocatechin gallate (EGCG) formulation

Epigallocatechin gallate (EGCG) is a potent polyphenoclic antioxidant extracted from green tea. Due to its antimutagenic and antitumor activities it is a promising candidate for use in topical formulations for skin cancer prevention. The overall objective of this dissertation was to develop a formulation suitable for the topical delivery of (EGCG). A high-performance liquid chromatography (HPLC) assay was developed to evaluate the possible degradation of EGCG from the various solvents used to incorporate it into topical formulations in the preformulation studies. This method was validated to establish linearity, precision, and accuracy and also was successfully applied to determine the stability of the finished formulations. First, the stability of EGCG in 0.05 M aqueous buffers in the pH range 3-9 was evaluated. The results indicated that the degradation of EGCG in aqueous media is strongly dependent on its storage conditions. EGCG exhibited its highest stability at low pH and 4°C. Stability studies of EGCG in organic solvents indicated that the degradation of EGCG can be reduced significantly. Furthermore, it was found that the addition of EDTA and butylated hydroxytoluene (BHT) resulted in an even greater stability of EGCG. Next, different types of polymers were investigated for their ability to form non-aqueous gels with glycerin, the solvent found most suitable for enhancing EGCG's stability. Methacrylic acid derivatives (Carbopols RTM) were found to be the most efficacious gelling agents. Carbopol RTM 974, best known for its mucoadhesive properties, was found to produce the highest viscosity. In the last phase of the study EGCG was incorporated into the anhydrous formulations. The in vitro release characteristics were then evaluated using a Franz-type diffusion cell system. The results indicated that the release of EGCG obeys the Higuchi equation. Furthermore, it was found that a stable EGCG formulation in glycerin can be developed.