On the Use of a Twin Screw Extruder for Continuous Solid Feeding and Dissolution for Continuous Flow Processes

The progress from batch to continuous manufacture of pharmaceuticals has highlighted the challenging area of dosing solid material directly, efficiently, and accurately into continuous flow systems for workup in flow chemistry processes. Twin screw extruders (TSEs) have the advantage of decoupling the dry (loss in weight feeder end) from the wet (liquid input) to prevent solids from sticking around the feeder, thereby enabling continuous solid feeding into a flow process. In this study, the feasibility of a 16 mm TSE as a solid feeder is investigated, and efficient dissolution of an example active pharmaceutical ingredient (API) is demonstrated. Paracetamol and an 80:20 mixture of water and isopropyl alcohol are the solute and solvent, respectively. The concentrations of paracetamol during dissolution experiments are monitored using an in-line UV attenuated total reflectance probe connected to a spectrometer, and the dissolution kinetics is extracted. Full dissolution of powder particles is obtained within the residence time of the TSE. However, full dissolution of granular particles is achievable by lowering the feed rate or having a higher barrel temperature. We have, for the first time, proposed a methodology of estimating the power density of a TSE, enabling a fair comparison of the dissolution rates for this continuous system and a batch stirred tank.