Application of a Dissolution-Diffusion Model to the Release of 5-Fluorouracil from Polymer Microspheres

作者：Kim Kwang Seok; Simon Laurent^*

来源：Chemical Engineering Communications, 2012, 199(5): 587-599.

DOI：10.1080/00986445.2011.604811

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

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 x 10(-15) m(2)/s, and 17.60 g/m(3) h, 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.

• 出版日期2012