Application of Twin-Screw Melt Granulation to Overcome the Poor Tabletability of a High Dose Drug

Pharmaceutical tablet manufacturing has seen a paradigm shift toward continuous manufacturing and twin-screw granulation-based technologies have catalyzed this shift. Twin-screw granulator can simultaneously perform unit operations like mixing, granulation, and drying of the granules. The present study investigates the impact of polymer concentration and processing parameters of twin-screw melt granulation, on flow properties and compaction characteristics of a model drug having high dose and poor tabletability. Acetaminophen (AAP) and polyvinylpyrrolidone vinyl acetate (PVPVA) were used as a model drug (90-95% w/w) and polymeric binder (5-10%w/w), respectively, for the current study. Feed rate (similar to 650-1150 g/h), extruder screw speed (150-300 rpm), and temperature (60-150 degrees C) were used as processing variables. Results showed the reduction in particle size of drug in the extrudates (D-90 of 15-25 mu m from -80 mu m), irrespective of processing condition, while flow properties were a function of polymer concentration. Overall, good flowability of the products and their tablets with optimum tensile strength can be obtained through using high polymer concentration (i.e., 10% w/w), lower feed rate (similar to 650 g/h), lower extruder screw speed (150 rpm), and higher processing temperatures (up to 120 degrees C). The findings from the current study can be useful for continuous manufacturing of tablets of high dose drugs with minimal excipient loading in the final dosage form.