Mechanistic studies of macromolecular drug release from macroporous polymers. II. Models for the slow kinetics of drug release

Ronald A. Siegel, Robert Langer

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

The release of protein drugs such as bovine serum albumin (BSA) from poly mers such as macroporous poly(ethylene-co-vinyl acetate) (EVAc) matrices has been shown previously to be much slower than would be predicted from simple considerations of aqueous diffusion. Since drug is released through waterfilled pores, it is necessary to determine the mechanism underlying release retardation. Three mechanisms are considered: (1) concentration-dependent diffusion, (2) random pore topology, and (3) constricted pore geometry. The first two mechanisms are shown to be insufficient, in themselves or together, to account for the order of magnitude of retardation that is observed. The third mechanism, pore constrictions, can account for arbitrarily high retardations. Since the three mechanisms are essentially independent, their contributions to retardation can be considered to be multiplicative.

Original languageEnglish (US)
Pages (from-to)153-167
Number of pages15
JournalJournal of Controlled Release
Volume14
Issue number2
DOIs
StatePublished - Oct 1990

Keywords

  • concentration dependent diffusion
  • constricted pore geometry
  • random pore topology
  • retarded diffusion, drug release modeling

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