Unified polymer erosion model for pulsatile drug delivery

By stacking individual drug layers between degradable polymer membranes, unique individual drug doses may be delivered in pulsatile fashion from a simple polymer laminate. This strategy may be limited, however, by the bulk-eroding nature of most hydrolytically degradable polymer membranes. Current models classify polymer films as either bulk- or surface-eroding and are not suited for modeling intermediate erosion behaviors, though many polymer coatings demonstrate erosion behavior between these extremes. Moreover, no metric exists for quantifying the bulk- vs. surface-eroding behavior of a membrane. This paper introduces a stochastic, Monte-Carlo style model which calculates the erosion profile of a degradable polymer membrane based on its moisture diffusion coefficient, membrane thickness, and a modified degradation rate constant, generating erosion profiles spanning the continuum from strongly bulk-eroding to strongly surface eroding based on the membrane's Damkohler number. The nature of this erosion is quantified by the Bulk Erosion Factor (BEF), the factor by which the polymer's mean erosion time exceeds the surface-eroding ideal. The model is compared against experimental examples of intermediate erosion behavior and used to correlate the Damkohler number to BEF, the relative membrane percolation time, and the resulting pulsatility of drug release. (C) 2016 Elsevier B.V. All rights reserved.