The purpose of this study was to investigate the effect of reducing drug proportion and mixing time on the content uniformity of a low dose drug. Buspirone hydrochloride was used as a model drug and was mixed with other ingredients in two different concentrations (0.5% w/w and 5% w/w) in a T. K. Fielder high shear mixer at a high impeller speed (522 rpm) and a high chopper speed (3600 rpm) up to 32 min. Samples were withdrawn from nine locations in the mixer at specific time points using a side-sampling thief probe. The final blends at 32 min were compressed using an instrumented tablet press. Tablets were sampled at the beginning, middle, and end of the compression run. The statistical results indicated that the drug proportion had a significant effect on the content uniformity of the powder blend and the corresponding tablets. For this study, the optimum time to mix the 0.5% w/w formulation was after 8 min while it was only 1 min for the 5% w/w formulation. The RSD of buspirone hydrochloride contents of tablets decreased as the compression run was toward its end. Uniformly mixed blends produced tablets that met the USP XXIV content uniformity requirements.