5-Fluorouracil release from chitosan-based matrix. Experimental and theoretical aspects

Abstract

A series of four drug release formulations based on 5-fluorouracil encapsulated into a chitosan-based matrix were prepared by in situ hydrogelation with 3,7-dimethyl-2,6-octadienal. The formulations were investigated from structural and morphological aspects by FTIR spectroscopy, polarized light microscopy and scanning electron microscopy. It was established that 5-fluorouracil was anchored into the matrix as crystals, whose dimension varied as a function of the crosslinking density. The in vitro drug release simulated into a media mimicking the physiological environment revealed a progressive release of the 5-fluorouracil, in close interdependence with the crosslinking density. In the context of Pharmacokinetics behavioral analysis, a new mathematical procedure for describing drug release dynamics in polymer-drug complex system is proposed. Assuming that the dynamics of polymerdrug system's structural units take place on continuous and nondifferentiable curves (multifractal curves), we show that in a one-dimensional hydrodynamic formalism of multifractal variables the drug release mechanism (Fickian diffusion, non-Fickian diffusion, etc) are given through synchronous dynamics at a differentiable and non-differentiable scale resolutions. Finally, the model is confirmed by the empirical data.