Controlled release of vancomycin from PCL microcapsules for an ophthalmic application

The aim of the present work is to identify, by means of mathematical modelling, effective strategies to keep vancomycin (a glycopeptide antibiotic) at the desired therapeutical concentration in the aqueous humour of the eye for the necessary period of time. Controlled release from polycaprolactone (PCL) microcapsules is here proposed since it represents a continuous release process, that is described by means of a mathematical model. The diffusion of the active principle from the microcapsules is modelled both considering a unique class of particles characterised by average properties and the real particle distribution; the diffusivity of the drug is not given as a numerical input but is modelled considering its movement among the empty spaces of the polymeric chains of the coating. At first a simple in vitro release process, in an aqueous solution, without the degradation of the active principle, is considered and through a comparison with experimental release data the diffusivity of vancomycin within the coating is determined. Then, after acquiring this information on the transport properties of vancomycin, the in vivo model of practical interest is considered: it describes the accumulation of the drug, released by the microcapsules, in the aqueous humour of the eye, where it undergoes degradation. The temporal curve of drug concentration is obtained for different investigated conditions and qualitative and quantitative suggestions are given for this ophthalmic therapy. (C) 2008 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.