Simplified end-to-end continuous manufacturing by feeding API suspensions in twin-screw wet granulation.

This study focussed on investigating the coupling of continuous manufacturing of drug substance and continuous manufacture of drug product. An important step in such an integrated end-to-end continuous manufacturing was envisioned by dosing the API as suspension into a twin-screw wet granulation process. To achieve this goal, a model drug substance (ibuprofen) was fed as a concentrated aqueous suspension (50% w/w) into a twin-screw granulator and compared against traditional solid feeding of the model drug substance to meet a target ibuprofen load of 60% w/w in the formulation. Granulation and compaction behaviour were evaluated to determine the impact of feeding API as suspension in twin-screw wet granulation on the critical quality attributes of the drug product. It was demonstrated that the ibuprofen suspension feed is comparable with the ibuprofen dry blend feed in twin-screw wet granulation. Next to enabling end-to-end continuous manufacturing, API suspension feed in twin-screw wet granulation could afford a number of additional advantages including manufacturing efficiency by removing the drying step for API, or overcoming processing issues linked to the bulk properties of the API powder (e.g. flowability).