process gram-size batches. For example, the Thermo Scientific bench-top Haake
MiniLab micro compounder processes samples as small as 5 grams. Others options include the Rondol Microlab 10 mm and DSM Xplore Xcelera (see the “Big ideas for small machines” article in Compounding World, December 2011, page 21). A limitation of some of these very small extruders is
Leistritz’s Nano-16 twin screw extruder can process batches as small as 20-100 grams
manufacturers must document the materials of construction used and their raw material sources. Processors using the equipment must develop cleaning procedures for each formulation, and validate or prove that they are effective. Materials of construction used in extruders for
medical applications generally require smoother surfaces than typical plastic applications, since proces- sors must document cleanability, notes Johannes Donner, process engineer for hot-melt extrusion at Coperion. Unlike most plastic compounds, pharmaceuti- cal compounds are typically water-soluble, and proces- sors generally use water to wash extruders between different products. Today’s extruder and peripheral equipment designs, such as modular components with quick disconnects that were built for easy cleaning in the plastics industry, translate well into the cleanability needs of the pharmaceutical industry, adds Donner. Drug products for human use must be manufactured
in a clean room, which controls the environment to avoid contaminating the drug. It also affects aspects of the equipment such as how maintenance is performed. The extruder drive can be placed outside the clean room, with the processing section inside, notes Donner. HME for drug-eluting devices that are not sterilized must be done in at least a class 100,000 clean room, which is equivalent to ISO 8. Clean room classes range from ISO 1, which is the most stringent, to ISO 9, which is the least stringent.
Twin-screw extruders in medical development Because many APIs are expensive or are only available in limited quantities, developers often want to use as small a sample as possible in the R&D process. Micro-compounding extruders have been designed to
22 COMPOUNDING WORLD | June 2012
that they do not scale up to commercial size. However, extruder manufacturers in the past few years have been introducing extruders in the 12-20 mm diameter range that run at rates appropriate for pharma process development or small-scale commercial runs. These extruders typically have the same geometry (OD/ID ratio, similar screw profile and mixing elements) as their larger-scale counterparts, which enables scale up to commercial size extruders with diameters in the range of 26 mm and larger. Leistritz’s Nano-16 twin screw extruder, with 16 mm
diameter screws, 1.2 OD/ID ratio and 1 cc/diameter free volume, is targeted for applications such as this and can process batches as small as 20-100 grams. Batches in the 20-50 gram range are made possible using Leistritz’s patented plunger feeder that pushes materials into the feeding zone at a specified rate, less than the rate of the feed screw, to allow starve feeding. The Nano-16 also uses tri-lobal screw elements
because of the geometric differences inherent with the smaller OD/ID ratio, explains Charlie Martin, president of the US operations of Leistritz. The Nano-16 design with the plunger feeder replicates the mechanisms of production-scale equipment, and helps developers determine if an API-excipient formulation is amenable to hot-melt extrusion, explains Martin. The Nano-16 can also be scaled up to Leistritz’s Micro-18 mm TSE with bi-lobal screw elements and a 1.5 OD/ID ratio by using the same motor, gearbox, and controls and exchanging the process section. Coperion offers an 18-mm co-rotating twin-screw
ZSK for the pharmaceutical development market. It has the same 1.55 OD/ID ratio as the company’s larger Mega compounding extruders. The barrel heating and cooling system has been redesigned to increase temperature control precision to +/- 1°C and to give the extruder the ability to change temperatures more quickly during lab experiments, which is especially important when working with expensive APIs. Other twin-screw extruders in this size range include
the Thermo Scientific Pharma 16, C.W. Brabender’s 12-mm and 20-mm TSEs, and Steer’s O-Micron 12-mm TSE. Process developers can use these smaller-scale extruders to refine formulations and run processing trials to optimize variables such as temperature and