Track: Manufacturing and Analytical Characterization - Chemical - Drug Product Manufacturing and Development - Process Optimization
Category: Poster Abstract
Flood Feeding Small Batches on a Co-Rotating Intermeshing Twin-Screw Extruder.
Purpose: Describe how to successfully process small batches on a co-rotating twin-screw extruder (TSE) utilizing a flood feeding method to evaluate formulation efficacy in an R&D environment. Analyze results from flood feeding several different materials. Find the rate range of flood fed systems to help determine viability of a continuous extrusion process when only a small batch is available for testing. Twin-screw extruders are typically starve fed and typically over-torque when flood fed. Methods: The Leistritz ZSE-16 mm co-rotating TSE at 26:1 L/D (1.2 OD/ID, 42 Nm of torque capacity) was used with two different screw designs (figure 1 a&b). A hopper was placed at the feed barrel and a 50 g batch was input into the hopper and screws. The extruder screw rpms forwarded the materials for processing. Several conditions (table 1) of 50-300 rpm, and a flat temperature profiles of 160 °C were used. Materials with different particle sizes and bulk densities were chosen including HPMC, Copovidone, and Unipurge (table 2). The rate was checked with a 60 second catch sample for each material and rpm. Results: The two basic feeding methods of extruders include flood feeding and starve feeding. Flood feeding is typically used in single screw extrusion where the feed hopper is filled and the screw rpm determines the feed rate. Starve feeding is typically used in twin screw extrusion where a feeder is used to meter the material into the system at a predetermined rate where rpm and throughput are independent of each other. On a TSE, flood feeding is atypical because it will normally over-torque the machine.
Pharmaceutical processes in early development stages usually require minute quantities of materials to be processed. There have been challenges evaluating small batches at these low quantities. Auger style feeders often require 200+ grams of material to reach equilibrium. Flood feeding a twin-screw extruder has previously not been evaluated to determine viability due to torque limitations. The shallow flight depth (1 mm) and high torque capacity of the ZSE-16 mm TSE, plus an appropriately designed feed section of the screw allows for operation like this.
A screw was designed to limit the intake of material using 10 mm pitch conveying elements while still creating the downstream effects of a starve fed process allows for the benefits of varying degree of fill and mixing efficiencies (figure 1a). HPMC and Copovidone, both powders, showed similar effects vs. rpm. at 300 rpm and higher. The high rpm would create an agitation/propeller effect and aerate the powder preventing it from being taken away as efficiently. This can be seen with Copovidone from 150 to 300 rpm where the rate decreases from 9.2 g/min to 8.3 g/min. It can also be seen less drastically for the HPMC which only slightly increased from 15 g/min to 16.4 g/min (Table 1 & Figure 2). This is because the particle size and bulk density were both higher than the Copovidone. All small batches of 50 grams were successfully tested and approximately 2-3 grams were lost on the screws for each. The extrudate was amorphous and the color indicated little to no degradation. Unipurge, a polyethylene-based purge compound, was pelletized to 1 mm particle size to be able to fit into the system. Because of the low surface area, the pellets were not affected in the same way at higher rpm and the rate between different rpms consistently increased.
Overall, the residence times were comparable to similar conditions with a starve fed system where 4 g/min of copovidone at 200 rpm produced a residence time of 130 seconds. A second screw with a traditional feeding section will be evaluated in future studies (figure 1b). Conclusion: Implementing a flood feeding technique on a twin screw extruder with a specific screw design designed to limit the intake of material and still allow for the benefits of varying degree of fill and mixing efficiencies has proven to be effective feeding low rates. Rpm’s slower than 50 rpm can achieve rates even lower but the residence time will increase and might potentially cause unnecessary thermal exposure. However, the degree of fill will remain constant and the energy imparted from the screws will remain low. The reduction in waste that accompanies auger style feeders where the material coats the feeder hopper and auger(s) presents a benefit when only limited quantities of expensive APIs are available. Overall, this feeding method enables an efficient method to process low volume pharmaceutical batches via extrusion.