A mechanistic model of controlled drug release from polymer millirods: Effects of excipients and complex binding

Fangjing Wang, Gerald M. Saidel, Jinming Gao

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The incorporation of different cyclodextrin (CD) excipients such as HPβ-CD, β-CD, γ-CD or α-CD into polymer millirods for complexing β-lapachone (β-lap), a potent anti-cancer drug, significantly improved the drug release kinetics with various drug release patterns. However, such a complex system requires a mechanistically based model in order to provide a quantitative understanding of the many molecular events and processes that are essential for the rational development of millirod implants. This study focuses on mathematical modeling of drug release from PLGA cylindrical millirods. This millirod system incorporates multiple components: a PLGA matrix; excipient in free and complex forms; drug in free, bound, and crystalline forms. The model characterizes many dynamic transport and complexation processes that include radial diffusion, excipient complexation and crystalline drug dissolution. Optimal estimates of the model parameters were obtained by minimizing the difference between model simulation and experimentally measured drug release kinetics. The effects of different drug loadings on the drug release rate were simulated and compared with other data to validate this model. Whereas our model can simulate all the experimental data, the Higuchi model can simulate only some of them. Furthermore, our model incorporates mechanisms by which the processes underlying drug release from a polymer matrix can be quantitatively analyzed. These processes include drug entrapment/dissolution in the matrix, drug recrysallization, and supersaturation. This modeling study shows that complex binding capacity, which affects drug initial conditions, drug-polymer interactions, and bound drug behavior in aqueous solution, is crucial in controlling drug release kinetics.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalJournal of Controlled Release
Volume119
Issue number1
DOIs
StatePublished - May 14 2007

Keywords

  • Cyclodextrin inclusion complex
  • Drug release
  • Excipients
  • Mathematical model
  • PLGA millirods
  • Parameter estimation

ASJC Scopus subject areas

  • Pharmaceutical Science

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