Parameter estimation methodology in a model of hydrophobic drug release from a polymer coating.

The TAXUS Express coronary artery stent delivers a sustained dose of a hydrophobic drug (paclitaxel) from a hydrophobic polymer coating (poly(styrene-isobutylene-styrene), SIBS). It is known that particles of concentrated drug are dispersed throughout the polymer coating, however, the mechanism by which drug exits the polymer matrix is not fully characterized. In this work, mathematical models were applied to in vitro controlled release data obtained from 8.8, 25 and 35% loadings of drug in polymer. Models that accounted for release by different mechanisms were tested. It was observed that Fickian diffusion, dissolution and osmotic gradient models were capable of fitting the data equally well. It was also possible to fit the data with a variety of parameter combinations, even if the values of some parameters were unlikely. We use the example of Paclitaxel release from the SIBS matrix to discuss important considerations in fitting controlled release data with mechanistic models. (c) 2009 Elsevier B.V. All rights reserved.