Mechanistic relationships between polymer microstructure and drug release kinetics in bioerodible polyanhydrides

Abstract

This work investigates the relationship between polymer microstructure and drug release kinetics in the bioerodible polyanhydride system, poly[(1,6-bis- p-carboxyphenoxy hexane)–co-(sebacic anhydride)] (CPH–SA). Model drugs, p-nitroaniline (PNA) and disperse yellow 3 (DY), were selected based on compatibility with CPH and SA, respectively. The polymer microstructure and compatibility of the drug with the constituent monomers were determined to have significant influence over the release kinetics of the drugs studied. Polymer systems with homogeneous microstructure, poly(SA) and 50:50 CPH–SA, showed simultaneous polymer degradation and drug release, although the solubility of the drug in the polymer influenced the shape of the release profiles. For the heterogeneous copolymers, 20:80 and 80:20 CPH–SA, individual monomer release kinetics demonstrated the effects of drug partitioning within a phase-separated microstructure. The PNA molecules partition preferentially into the CPH microdomains in the 20:80 CPH–SA copolymer while the DY molecules partition preferentially into the SA microdomains in the 80:20 CPH–SA copolymer. These studies suggest that the drug release mechanism is driven by polymer microstructure, compatibility of the drug with the constituent polymer phases, and solubility of the drug within the polymer. A thorough understanding of drug–polymer interactions as well as the polymer microstructure will pave the way for more accurate predictions of drug release from bioerodible polyanhydrides.