Integrated continuous melt granulation-based powder-to-tablet line: Process investigation and scale-up on the same equipment

Abstract

In the last decades, continuous manufacturing (CM) has become a research priority in the pharmaceutical industry. However, significantly fewer scientific researches address the investigation of integrated, continuous systems, a field that needs further exploration to facilitate the implementation of CM lines. This research outlines the development and optimization of an integrated, polyethylene glycol aided melt granulation-based powder-to-tablet line that operates fully continuously. The flowability and tabletability of a caffeine-containing powder mixture were improved through twin-screw melt granulation resulting in the production of tablets with improved breaking force (from 15 N to over 80 N), excellent friability, and immediate release dissolution. The system was also conveniently scaleable: the production speed could be increased from 0.5 kg/h to 8 kg/h with only minimal changes in the process parameters and using the same equipment. Thereby the frequent challenges of scale-up can be avoided, such as the need for new equipment and separate optimization.

Keywords: Continuous manufacturing; Integrated continuous process; Melt granulation; Scale-up; Twin-screw granulation.