Increasing attention has been given to spray drying because of its popularity in the manufacturing of various powders with prerequisite quality. A large number of theoretical and experimental studies have been published during the last five decades to study spray-drying operations. Despite this progress, there is still lack of information on the selection of an accurate and simple drying kinetics model to characterize the droplet drying process. This article has particularly focused on the comparison of two simple and effective drying kinetics models: the characteristic drying-rate curve and reaction-engineering approach (REA) models. This article reported mathematical models that can be used to design the spray-drying operation and to predict the particle's characteristics for realistic dryer-wide situations. Both the physical and biochemical quality attributes were investigated regarding their sensitivity to the model parameters used in the two drying kinetics models. The REA model was found to deliver more realistic predictions during the modeling of the droplet drying process for all the sets of conditions tested.