The discrete phase model (DPM) has been widely used in CFD simulations to track discrete particles or droplets in a continuum fluid filed. This powerful technique, however, may face tremendous difficulty in tracking droplets flying through chambers with significantly different sizes. In such cases, it becomes very challenging to develop effective mesh for the big and small chambers together with the transition zone that can ensure solution convergence within reasonable computational time. In this work, a systematic method is introduced to tackle this problem. This method allows simulation of different sized chambers separately to avoid the meshing difficulty. A unique coupling approach offers smooth transition of droplets from one chamber to the other with rigorous conservation of their mass, energy and momentum. The effectiveness of the method is demonstrated through the simulation of skim milk droplet drying in a mono-disperse droplet spray dryer (MDSD), where droplets must pass through a small dispersion chamber before entering the main big drying chamber. For the first time, droplet drying process from exiting nozzle to the arrival at the dryer outlet can be simulated. The new model can be used in the future to optimize the spray drying process. (C) 2019 Elsevier Ltd. All rights reserved.