Model compound release from DL‐lactide/ε‐caprolactone copolymers and evaluation of specific interactions by molecular modeling

Abstract

AbstractThe applicability of poly(DL‐lactide‐co‐ϵ‐caprolactone) copolymers P(DL‐LA/CL) for controlled‐release devices was evaluated. The copolymers of DL‐lactide and ϵ‐caprolactone were polymerized in bulk using Sn(II)octoate as the initiator. The release of three model compounds, theophylline, propranolol hydrochloride, and lidocaine (10 wt%), from high‐lactide content copolymer was studied. The results showed that the copolymer with only minor caprolactone content was not suitable for controlled release of these small‐molecular weight model compounds in matrix‐type devices. A burst in the release rate was observed when the degradation of the matrix replaced diffusion‐controlled release. Increasing the permeation properties of the copolymer matrix through blending and using a different comonomer ratio with an increased caprolactone content were both studied. A release that was more controlled but relatively slow was obtained by using copolyester blends as release matrices. Hydrolytic degradation of the copolymers was also recorded, and the copolymers were found to be very susceptible to hydrolytic chain scission at 37°C. Molecular modeling studies were performed to study the interactions between the theophylline model compound and the homo‐ and copolymers of lactide and ε‐caprolactone units. In agreement with experimental results, the calculations showed increasing interaction between theophylline and the polymer matrix as a function of increasing amount of lactide units. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1–9, 2002