In a typical aqueous nasal suspension manufacturing process, the homogeneity of the active pharmaceutical ingredient (API) dispersion in a premix vessel is determined merely by visual observation. In this study, to better demonstrate in-process control, Raman spectroscopy was developed as a process analytical tool (PAT) to monitor the real-time API dispersion homogeneity in the active premix process. The end-point variations of the API dispersion as a function of the surfactant type, surfactant concentration, and agitation speed were evaluated by dispersive Raman spectroscopy in combination with multivariate analysis for both lab-scale and pilot-scale batches. The optimal surfactant concentration and type were determined to be 0.2% surfactant A for the active dispersion based on a quantitative end-point comparison. In addition, a chemometric model was developed successfully for the real-time prediction of API concentration in the active premix, with a root mean squared error of prediction (RMSEP) of 5.4%. In conclusion, Raman spectroscopy has proven to be a viable PAT tool to qualitatively and quantitatively assess the active premix homogeneity in an aqueous nasal suspension manufacturing process. In the future, this method can potentially be used in the commercial manufacturing process for in-process control of the dispersion homogeneity of the suspension. Copyright © 2011 John Wiley & Sons, Ltd.