Twin screw granulation as a simple and efficient tool for continuous wet granulation.

The modification of a twin screw extruder for continuous wet granulation was investigated. Modification of the extruder setup as well as the screw design allowed the continuous wet granulation of alpha-lactose monohydrate without the need of a wet sieving step. The robustness of twin screw granulation was evaluated by studying the influence of processing parameters and formulation variables on the process performance and on the properties of alpha-lactose monohydrate granules and tablets. The process reproducibility during long term production was evaluated. Screw speed (200-450 rpm) and total input rate (5.5-9.5 kg/h) had no significant influence on the granule properties, while the water concentration during granulation influenced the process as well as the granule properties. At a water concentration (calculated on wet granule basis) of 5.5-8.5%, continuous twin screw granulation of alpha-lactose monohydrate 200 M was feasible and the granules obtained had good properties. PVP addition mainly affected tablet properties. Tablets made from granules containing 2.5% PVP had a tensile strength above 0.94 MPa, a friability below 1% and a disintegration time ranging between 495 and 576 s. Tablets containing hydrochlorothiazide complied with the dissolution requirements as 60% was released after 5 and 15 min from tablets without PVP and with 2.5% PVP, respectively. No problems were observed during continuous twin screw granulation over a period of 8h and the granule and tablet properties were reproducible throughout the process. These results indicated that twin screw granulation is an efficient tool for continuous wet granulation.