The influence of localization (intragranular, split or extragranular) of three superdisintegrants (croscarmellose sodium, crospovidone, sodium starch glycolate) on granules and tablets after twin-screw granulation was studied. The aim was to find a suitable disintegrant type and disintegrant localization for lactose tablets manufactured with different hydroxypropyl cellulose (HPC) types. The disintegrants were found to decrease the particle size in granulation, where sodium starch glycolate had the lowest influence. The tablet tensile strength was not influenced strongly by the disintegrant type or localization. By contrast, the disintegration was dependent on the disintegrant type as well as the localization, where sodium starch glycolate performed worst. Intragranular croscarmellose sodium and extragranular crospovidone were identified as beneficial for chosen conditions because a satisfying tensile strength in combination with the fastest disintegration was found. These findings were achieved for one HPC type and the suitability of the best disintegrant-localization-combinations was confirmed for another two HPC types.