In the past, laboratories had only small-scale batch mixers for formulation development, but during the past few years, several extruder manufacturers have introduced laboratory-scale TSEs suitable for API quantities as small as 5–20 g, thus enabling pharmaceutical manufacturers to test new drug candidates on a TSE.
Mid-size extruders in the range of 12–20 mm in diameter that have similar design attributes to larger extruders can be used for process development in preparation for scale-up to pilot-size or small commercial-size TSE in the range of 26–32 mm and perhaps eventually to larger commercial-size TSE in the range of 40–70 mm. Extruder manufacturers, such as Coperion, C.W. Brabender, Leistritz, Steer America, and Thermo Scientific, offer extruders for the pharmaceutical industry in the mid-size range that can be used for process development and clinical-scale trials as well as small-scale commercial runs. In some cases, drug manufacturers may even choose to use these mid-size extruders for commercial production.
Mid-size extruders are useful for determining the "extrudability" of a formulation and identifying the extrusion conditions needed for good mixing, says Stefan Gebhardt, head of extrusion systems for pharma and food at Coperion. Parameters can include the extruder's screw design, temperature profile, shear rate, and throughput.
The processing window for pharmaceutical excipients is narrow, and in some cases, a few degrees in temperature change can have a dramatic affect on material viscosity, says Gebhardt. In addition, excipients and APIs may be sensitive to degradation from heat or shear.
Determining the appropriate temperature profile in a TSE, therefore, is an important parameter in running process experiments. In the processing laboratory, researchers may want to run multiple temperature profiles in a short period of time and without shutting down the extruder to minimize the amount of experimental material needed. To enable this approach, Coperion recently developed an improved temperature-control system using cartridge heaters and a water-cooling system that allows its mid-size extruder to reach stable temperature conditions more quickly.
Processing laboratories also have a need to be able to quickly clean the screw or change the screw profiles of an extruder between experiments. Several mid-size extruders have a clamshell barrel design in which the barrel cover opens on a hinge to allow easy access for cleaning and screw changes.