A high energy input during pharmaceutical formulation is capable of decreasing the crystallinity of compounds in the product. The presence of the amorphous form can cause serious problems at any stage of the formulation. Crystallinity changes of a model powder mixture containing clopidogrel bisulfate (CLP) and a colloidal silicon dioxide as additive were investigated during a long-time co-grinding process. The crystallinity of CLP was reduced sigmoidally by co-grinding with longer co-grinding time. X-ray powder diffraction and differential scanning calorimetry examinations confirmed that the product had become totally amorphous after four hours of grinding. Thermogravimetric results proved that no major mass reduction happened and FT-IR changes referred to formulation of a secondary bond between the components.