High‐order simulation of polymorphic crystallization using weighted essentially nonoscillatory methods

Abstract

Abstract Most pharmaceutical manufacturing processes include a series of crystallization processes to increase purity with the last crystallization used to produce crystals of desired size, shape, and crystal form. The fact that different crystal forms (known as polymorphs) can have vastly different characteristics has motivated efforts to understand, simulate, and control polymorphic crystallization processes. This article proposes the use of weighted essentially nonoscillatory (WENO) methods for the numerical simulation of population balance models (PBMs) for crystallization processes, which provide much higher order accuracy than previously considered methods for simulating PBMs, and also excellent accuracy for sharp or discontinuous distributions. Three different WENO methods are shown to provide substantial reductions in numerical diffusion or dispersion compared with the other finite difference and finite volume methods described in the literature for solving PBMs, in an application to the polymorphic crystallization of L ‐glutamic acid. © 2008 American Institute of Chemical Engineers AIChE J, 2009