Simplified, high drug loaded formulations for use in twin-screw granulation and tableting were introduced, using the plastically deforming drug ibuprofen. This concept was enlarged by application of hydrochlorothiazide, because opposed deformation behavior was expected to result in different product performances. In most instances the results differed. Critical quality attributes like granule size distribution, disintegration time, and tensile strength of tablets could be met. The study confirms the suitability of simplified formulation with differently behaving drugs for pharmaceutical product design in continuous manufacturing.