Abstract
Modeling release of small molecules from degradable microspheres is important to the design of controlled-release drug delivery systems. Release of small molecules from poly(d,l-lactide-co-glycolide) (PLG) particles is often controlled by diffusion of the drug through the polymer and by polymer degradation. In this study, a model is developed to independently determine the contributions of each of these factors by fitting the release of piroxicam from monodisperse 50-μm microspheres made with PLG of different initial molecular weights. The dependence of the drug diffusivity on polymer molecular weight was determined from in vitro release of piroxicam from monodisperse 10-μm PLG microspheres, and the polymer degradation rate was experimentally measured using gel permeation chromatography. The model also incorporates the effect of nonuniform drug distribution within the microspheres, which is obtained from confocal fluorescence microscopy. The model results agree well with experiments despite using only one fit parameter.
| Original language | English |
|---|---|
| Pages (from-to) | 149-158 |
| Number of pages | 10 |
| Journal | Journal of Controlled Release |
| Volume | 103 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 2 2005 |
Bibliographical note
Funding Information:This work was partly supported by NIH grant EB002878. We would like to thank Larry Markoski and Prof. Jeff Moore for helping us with their time and equipment to make SEC measurements. The piroxicam gift from Dongwha Pharmaceuticals is also gratefully acknowledged. Scanning electron microscopy was carried out at the Center for Microanalysis of Materials, University of Illinois at Urbana-Champaign, which is partially supported by the U.S. Department of Energy under grant DEFG02-91-ER45439.
Keywords
- Degradation
- Diffusion
- Modeling
- Nonuniform drug distribution
- Piroxicam
- Poly(lactide-co-glycolide) microspheres
ASJC Scopus subject areas
- Pharmaceutical Science