Application of a dissolution-diffusion model to the release of 5-fluorouracil from polymer microspheres

Kwang Seok Kim, Laurent Simon

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

A theoretical discussion of drug release from microspheres is provided and a model-based predictive algorithm developed. The model verification step includes literature data describing the release profile of 5-fluorouracil (5-FU) from poly(lactic acid) polymer. Material balance equations were written to describe drug transport from a porous sphere. The model included combined effects of dissolution, diffusion, and void fraction on the release of 5-FU and was validated against in vitro experimental data. Analyses, conducted on published 5-FU release test data, revealed that the process was governed by a dissolution-diffusion mechanism. Approximately 1.5 million microspheres were formed; the drug density, diffusivity, and dissolution rate constant were estimated at 1.110 g/cm 3, 2.324 × 10 -15 m 2/s, and 17.60 g/m 3h, respectively. The dissolution rate was faster than the rate of diffusion by a ratio of 12.79 to 1. Manipulation of the microsphere porosity was an effective way to influence the diffusion-controlled process. The procedure, outlined in the study, for estimating process properties will help fabricate microspheres that meet specific requirements.

Original languageEnglish (US)
Pages (from-to)587-599
Number of pages13
JournalChemical Engineering Communications
Volume199
Issue number5
DOIs
StatePublished - May 1 2012

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

Keywords

  • Diffusion
  • Dissolution
  • Drug delivery
  • Drugs
  • Mathematical modeling
  • Transport phenomena

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