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A Reappraisal of Drug Release Laws Using Monte Carlo Simulations: The Prevalence of the Weibull Function
Authors:Kosmidis  Kosmas  Argyrakis  Panos  Macheras  Panos
Affiliation:(1) Department of Physics, University of Thessaloniki, 54124 Thessaloniki, Greece;(2) School of Pharmacy, University of Athens, 15771 Athens, Greece
Abstract:Purpose. To verify the Higuchi law and study the drug release from cylindrical and spherical matrices by means of Monte Carlo computer simulation.Methods. A one-dimensional matrix, based on the theoretical assumptions of the derivation of the Higuchi law, was simulated and its time evolution was monitored. Cylindrical and spherical three-dimensional lattices were simulated with sites at the boundary of the lattice having been denoted as leak sites. Particles were allowed to move inside it using the random walk model. Excluded volume interactions between the particles was assumed. We have monitored the system time evolution for different lattice sizes and different initial particle concentrations.Results. The Higuchi law was verified using the Monte Carlo technique in a one-dimensional lattice. It was found that Fickian drug release from cylindrical matrices can be approximated nicely with the Weibull function. A simple linear relation between the Weibull function parameters and the specific surface of the system was found.Conclusions. Drug release from a matrix, as a result of a diffusion process assuming excluded volume interactions between the drug molecules, can be described using a Weibull function. This model, although approximate and semiempirical, has the benefit of providing a simple physical connection between the model parameters and the system geometry, which was something missing from other semiempirical models.
Keywords:drug release  Monte Carlo simulations  power law  Weibull function
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