The relationship between lubricant-mixing time and dissolution time was investigated, and we established a calibration model to predict dissolution time by near infrared (NIR) spectroscopy and the rationale of the prediction. The bulk powder consisted of theophylline, lactose, and potato starch were pre-mixed. After magnesium stearate (Mg-St) was added, the material was mixed for up to 180 min. The mixed powders were compressed to tablets and dissolution tests were performed. From each dissolution curve, 50% dissolution time (T50) was calculated. The NIR spectra of each tablet’s upper surface was measured and a chemometric analysis was conducted. With the extension of mixing time, T50 was prolonged. The Mg-St widely covered the surface of each particle of the bulk powder after material mixing. This coating effect may decrease the wettability of the particles and cause the prolongation of dissolution time. The T50 was predicted by NIR spectroscopy with chemometrics and a calibration model was established. The regression vector showed typical peaks derived from −CH group of Mg-St, and it is suggested that those peaks, which were caused by the thin layer extension of Mg-St particles over the particle surfaces of other materials, contributed to the prediction of T50 prolongation. These studies show the usefulness of NIR measurements to control the effect of a lubricant in the process of raw powder material mixing.

Mixing processes are important for making high-quality pharmaceutical formulations and are related to dissolution and chemical stability in pharmaceutical manufacturing.