Potential Use of Ethylene Vinyl Acetate Copolymer Excipient in Oral Controlled Release Applications: a Literature Review

Ethylene vinyl acetate copolymer (EVA) has a successful commercial history in the pharmaceutical industry as a controlled release excipient. The usage covers a wide spectrum of parenteral applications ranging from transdermal drug delivery, contraceptive insertions, subcutaneous implants and mucosal contact forms. The importance and prominence of EVA in parenteral applications has inspired researchers to study EVA-based controlled release systems in other areas. This paper summarizes the recent developments of EVA-based oral controlled release drug delivery systems. In these studies, the EVA-based drug delivery systems were mostly prepared by hot melt extrusion (HME). The results have showed that the in vitro/in vivo drug release profiles of EVA-based systems can be readily tuned to be suitable for oral administration with the addition of a secondary functional component. The biocompatibility and oral toxicity studies on EVA are also summarized. Results in Simulator of the Human Intestinal Microbial Ecosystem (SHIME) evaluation indicate that EVA does not enzymatically or chemically interact with the simulated intestinal fluid. EVA-based systems have shown great potential in controlled release of drugs for oral administration. INTRODUCTION ETHYLENE VINYL ACETATE COPOLYMER Ethylene vinyl acetate (EVA) is a copolymer of ethylene monomer and vinyl acetate (VA) monomer, as illustrated in Scheme 1. The polymer is made by free radical polymerization under high pressure conditions. Scheme 1. Reaction scheme of ethylene vinyl acetate copolymer polymerization EVAs are commonly available up to 40% vinyl acetate (VA). Since the reactivity ratio between ethylene and VA is close to 1, VA monomers are almost randomly distributed on the polymer backbone [1]. VA monomers distributed across the backbone impact the polymer’s melting point, percentage of crystallinity, and optical properties. The stiffness and hardness of the polymer decrease as crystallinity decreases. The addition of the VA monomer also increases the polarity of the polyethylene backbone and thus affects the solubility/diffusivity of small molecules within EVA and compatibility of EVA with other polymers. These property variations can be used to influence the drug release properties in pharmaceutical applications where EVA is used.