Continuous twin-screw wet granulation without adding granulation liquid.

Abstract

Granulation is a major focus of pharmaceutical R&D, as a key step in the development of solid pharmaceuticals. In parallel, the spread of continuous integrated powder-to-tablet production lines is also underway. In this research, a new wet granulation method has been investigated in terms of operation and scalability in a fully continuous powder-to-tablet line. The new wet granulation technique requires no addition of granulation liquid to the powder blend; thus, requires only minimal cooling after granulation, providing a more energy-efficient continuous integrated system for the pharmaceutical industry. This can be achieved by adding an excipient with a monograph and a high daily intake, potassium sodium tartrate tetrahydrate (PST), to the starting powder mixture. PST contains water of crystallization which is released by temperature, forming an in-situ granulation liquid during the process. This wet granulation-based technology produced granules with excellent flowability and immediate-release tablets exceeding 100 N breaking force and 1.5 MPa tensile strength. The continuous setup enabled easy scale-up from 0.5 to 10 kg/h using the same equipment and process parameters.