In pharmaceutical development, we encounter amorphous and disordered crystalline materialsin a number of ways like milling, wet granulation, drying and re-crystallization. From a pharmaceutical perspective, whenever amorphous material is present there must be a significant concern since, relative to the crystalline state, the amorphous state is less thermodynamically stable. As per regulatory requirements the amorphous phase generated may need to be quantified by using sensitive analytical tools. In the present study, amorphous content in crystalline form of Cefuroxime axetil drug substance was studied by different analytical techniques like Modulated Differential Scanning Calorimetry (MDSC) and Powder X-Ray Diffraction (PXRD). The characteristic glass transition (Tg) of amorphous Cefuroxime axetil is exhibited at about 74.8°C. Different concentrations of amorphous content in crystalline drug substance have been prepared and analysed. By using MDSC, a quantification method was developed based on the fact that the change in the specific heat at the glass transition is linearly proportional to the amorphous content. The linearity of amorphous content was established for crystalline drug substance using MDSC. Superiority of the MDSC has been justified over PXRD in terms of detection of low level of amorphous content in crystalline drug substance.