Assessing mixing uniformity of a powder blend in pharmaceutical formulation of a low dose potent drug is a very critical step, failing which the entire formulation needs to be reworked from the beginning. Thermal analytical methods like differential Scanning calorimetry [DSC] are rapid method requiring very lesser sample for quantification. In this project we have made use of enthalpy values obtained from DSC for estimation of mixing uniformity in powder blend mixed using high shear mixture granulator. Influence of various parameters like melting behavior of drug and excipients, bulk density of excipients and mixing time on the results of enthalpy values was also evaluated. The results from DSC analysis were further confirmed using HPLC analysis and a correlation was proposed between the two analytical methods. It was observed that at lower levels of drug i.e. 0.5%, 1% and 2%, the relative standard deviation values obtained using DSC were higher than that using HPLC but at concentration above 5% of drug, the results of DSC and HPLC were quite similar. It was concluded that DSC could reliably predict the uniformity of powder blend where drug loading was above 5%, however results accuracy was somewhat less below this level. (C) 2015 Elsevier B.V. All rights reserved.