Assessment of volumetric scale-up law for processing of a sustained release formulation on co-rotating hot-melt extruders.

Abstract

In this research, the volumetric scale-up law was assessed for its applicability to scale-up from a laboratory-scale extruder (11 mm diameter) to a pilot-scale extruder (16 mm diameter) with geometric similarity using low feed rates (0.1-0.26 kg/h at lab-scale). A sustained release formulation was extruded on both scales using scaled feed rates according to the volumetric scale-up law. The specific mechanical energies, drug solid-state, drug dissolution and the residence time distribution responses (i.e. axial mixing degree, mean residence time, width of distribution) were compared between both scales. The results showed that the difference in mean residence time between both scale extruders reduced with higher throughput and thus fill level. Overall, the specific mechanical energies (SME) were comparable between scales when using the volumetric scale-up law (i.e. applying scaling factor q = 3) and were exactly matching with a scaling factor of q = 2.6. Furthermore, plug flow conditions at lab-scale should be avoided before scaling up to obtain similar SMEs. The same degree of axial mixing (represented by the Peclet number) was demonstrated at a scaling factor of q = 2. If drug solid-state is a critical quality attribute (CQA), focus should be on the screw speed and cooling capacity of the larger scale extruder. The drug dissolution showed similarity between scales and was independent of drug solid-state for this formulation, indicating that successful scale-up was possible.