In respiratory drug delivery, porous, lipid-based microparticles have shown performance advantages over microcrystalline particles (Hirst et al, 2002). These engineered particles are manufactured by spray drying of emulsions or suspensions. The purpose of this work is to combine an understanding of underlying mechanisms with particle characterization data to develop models in support of a quality-by-design (QbD) approach to drug development Powders were manufactured using a laboratory scale spray dryer. A thermodynamic model was developed for the spray drying process, allowing prediction of outlet temperature and powder residual water content A stochastic model based on a Monte-Carlo simulator was developed to analyze the effects of relevant parameters on the aerodynamic size of the particles; modeled results were verified by comparison to measured aerodynamic size distributions of spray-dried powders These modeling techniques allowed rank-ordering of the relative importance of formulation and process variables, and aided in developing an understanding of the drying unit operation (C) 2010 Elsevier Ltd All rights reserved.