A new mathematical model quantifying drug release from bioerodible microparticles using Monte Carlo simulations.
OBJECTIVE
The major objectives of this study were to 1) develop a new mathematical model describing all phases of drug release from bioerodible microparticles; 2) evaluate the validity of the theory with experimental data; and 3) use the model to elucidate the release mechanisms in poly(lactide-co-glycolide acid)-based microspheres. METHODS; 5-Fluorouracil-loaded microparticles were prepared with an oil-in-water solvent extraction technique and characterized in vitro. Monte Carlo simulations and sets of partial differential equations were used to describe the occurring chemical reactions and physical mass transport phenomena during drug release.


RESULTS
The new mathematical model considers drug dissolution, diffusion with nonconstant diffusivities and moving boundary conditions, polymer degradation/erosion, time-dependent system porosities, and the three-dimensional geometry of the devices. In contrast with previous theories, this model is able to describe the observed drug release kinetics accurately over the entire period of time, including 1) initial "burst" effects; 2) subsequent, approximately zero-order drug release phases; and 3) second rapid drug release phases. Important information, such as the evolution of the drug concentration profiles within the microparticles, can be calculated. CONCLUSIONS; A new, mechanistic mathematical model was developed that allows further insight into the release mechanisms in bioerodible microparticles.
Siepmann
Juergen
J
College of Pharmacy, Freie Universitaet Berlin, Kelchstr. 31, 12169 Berlin, Germany. siepmann@zedat.fu-berlin.de
Faisant
Nathalie
N
Benoit
Jean-Pierre
JP
D001711:Biotransformation; D008863:Microspheres; D008956:Models, Chemical; D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*
D004364:Pharmaceutical Preparations