Manufacture of low-dose tablet products has always the uniformity challenge. The objective of this work was to investigate the influence of key process variables of a gentle-wing high shear mixer on the uniformity of 1.0% w/ w albuterol sulphate/microcrystalline cellulose blend. Albuterol sulphate and excipients were mixed at various impeller and chopper speeds from 0.5 to 30 min. Triplicate samples were taken from nine different positions in the mixer bowl and the albuterol content was analyzed spectrophotometrically. Long mixing time (15 min) was necessary to achieve proper blend uniformity at low speeds of impeller and chopper. Otherwise, when the high chopper speed was applied, demixing occurred after 8 min with low impeller speed and after 6 min with high impeller speed. Furthermore, ANOVA analysis indicated the significant effect (P ≤ 0.05) of impeller speed and mixing time on the uniformity of the powder blends. Finally, dry mixing of low-dose based formulations in a gentle-wing high shear mixer; improving the dispersion of drug particles and formation of stable interactive mixture upon suitable selection of process variables. This study make the process variables of gentle-wing mixer a better candidate for further investigation and optimization using quality by design approach.