Hydrophilic absorbable copolyester exhibiting zero-order drug release.

ABSTRACT

PURPOSE: A novel absorbable hydrophilic copolyester developed in our laboratory, amorphous 40/60 poly(ethylene diglycolate-co-glycolide), exhibits outstanding physical properties. Films made from this material appear fully transparent, colorless, soft and slightly elastic, but relatively strong and durable materials so that they can be potentially used as stand-alone devices in various in-vivo medical applications. In this study, in-vitro drug release characteristics of this copolyester were examined. METHODS: High Performance Liquid Chromatography was used to generate release profiles on selected non-steroidal anti-inflammatory agents, NSAIDs. In addition, dielectric relaxation spectroscopy, as well as mid- and near infrared spectroscopy, were used to study specific polymer chain interactions in water and buffer solution as a function of aging time at 37 degrees C. RESULTS: This copolyester, compression molded into a film, exhibited nearly constant in-vitro release of various hydrophilic and hydrophobic drugs. The release profile showed minimal or, in most cases, no burst effect. The effect was observed with the three NSAIDs that were tested as model compounds; however, this system may prove generally useful for other drug entities. In-vitro hydrolysis conducted at 37 degrees C on this hydrophilic copolyester revealed an unusually long induction period (no hydrolysis for up to 6 days), followed by the relatively rapid hydrolysis. Data from dipole relaxation spectroscopy indicated that the water molecules do not structurally associate with the polymer chains in phosphate buffer during initial hydrolysis period. CONCLUSIONS: The results suggest unique dynamics of water diffusion through the polymer matrix that may play a critical role in achieving controlled release properties. Furthermore, we suspect that the molecular interactions associated with this new synthetic absorbable material may find a critical utility in important medical applications.