Visit almost any modern compounding facility today, and you will find a twin-screw extruder pumping out plastic pellets. The most productive of these high-speed, energy-input (HSEI) extruders can produce over 50,000 kilograms of finished plastic compounds per hour. Thanks to their inherent process design flexibility, HSEI twin-screw extruders can perform a wide variety of compounding work, including straight mixing, polymerization, devolatilization, and reactive extrusion.

In recent years, HSEI twin-screw extruders have moved beyond their roots in plastics and made their way into a growing number of pharmaceutical and nanotechnology applications. As a more advanced alternative to batch mixing, HSEI machines are enabling pharma users to create sophisticated new dosage forms by compounding active pharmaceutical ingredients with polymers.  In the nanotechnology world, HSEI twin-screw extruders incorporate functional nanoparticles into the next generation of aerospace, electronics, and packaging materials.

Despite their outward differences, the pharmaceutical and nanotechnology applications have something in common from a compounding standpoint. Both rely on material feedstocks that are typically available in very limited quantities and are breathtakingly expensive, sometimes costing many thousands of dollars per gram. These two factors create a problem for traditional HSEI twin-screw extruders: Machines designed for production environments that measure output in thousands of hourly kilograms will not be much help in developing materials measured in grams. The solution to this problem of scale has for years been the use of various laboratory-size extruders that comfortably process as little as 0.5 kg per hour.

Unfortunately, lab-size extruders have had problems when it comes duplicating the technical characteristics of full-scale HSEI machines, in part because the feed mechanism and process section design of production-sized twin screws do not scale down easily.

Over the last year, however, Leistritz engineers have worked around the problems of scale to come up with a new lab-size twin-screw extruder design. This “nano” extruder features mechanical design and process innovations that allow it to mimic the technical capabilities of traditional HSEI twin-screw machines without leaving precious quantities of developmental materials behind in the hopper.

Here’s a closer look at the design of this nano-scale compounding hardware and how it can make a difference in the efficient development of new drugs and nanotech materials.

Twin-screw Extrusion Fundamentals

Before diving into the details of the nano-scale machine, let’s start with an overview of twin-screw technology fundamentals, which will help put some of the intrinsic differences between production and nano-scale extrusion in context.

Production HSEI twin-screw extruders and many small-scale models share a basic construction philosophy. They consist of segmented screw and barrel elements that can be configured to the job at hand. These modular screw elements are assembled onto a motor-driven shaft capable of rotating the screws with high torque forces, imparting energy into the material to be processed. The modular barrel elements that enclose the screws feature internal cooling bores for tight thermal control.

When corotated within the barrel, the screw elements exhibit pumping and self-wiping actions. The specific compounding tasks performed by the extruder depend on the lineup of screw elements. For example, elements in machine’s process section can be tailored specifically for mixing or for devolatilization. Discharge elements downstream in the process section typically build and stabilize pressure (Figure 1 shows typical screw segments and functions).

Figure 1. Pressure Gradient in a Twin-Screw Extruder

The free volume available within the process section is directly related to the ratio of the screw’s outside diameter to its inside diameter (OD/ID) or, put differently, the ratio of the diameter around the screw flights to the screw’s root diameter. The torque-limiting factor in twin-screw extruders depends on the diameter of the screw shaft and the cross-sectional geometry of the shafts. For example, deeper screw flights result in more free volume but less torque because the deep flights reduce the screw shaft’s diameter.

Based on the use of a symmetrical splined shaft, an OD/ID ratio of approximately 1.55/1 historically has been considered to offer the best balance of torque and volume. In recent years Leistritz has developed new asymmetrical splined screw shafts that result in a more favorable volume-torque balance and potentially higher throughput rates. These asymmetrical shafts offer OD/ID ratios of 1.66/1 without sacrificing torque.

Conventional HSEI twin-screw extruders are starve fed with less material than the screws can handle at any specific time. Their output rate is determined by one or more feeders metering combinations of pellets, liquids, powders, and fibers into the process section. The rpm of the HSEI screw remains independent from the feed rate and is set to optimize compounding efficiencies.

By controlling pressure gradients with the barrel, starve feeding allows different fillers and other ingredients to be fed sequentially into downstream barrel sections. Sequential feeding is the key to many of the high-tech polymer compounds on the market today.

Nano Compounding: A New Mind-set

In high-volume production runs, the free volume, torque, and starve-feeding parameters are designed as a system with an eye toward maximizing throughput rates while maintaining product quality. A different mind-set and methodology are required in compounding pharmaceutical and nanotech materials. In these applications, the goal is to minimize the waste of rare, expensive materials while effectively evaluating the extrusion process and providing a route for future scale-up.

In many ways, this mind-set is uncharted territory that required a rethinking of the extruder’s process section design and feeding system. What Leistritz engineers came up with is a twin-screw extruder with segmented 16-mm OD screws and a 1-mm flight depth. Its 1.2/1 OD/ID ratio results in a free volume of approximately 1 cc/diameter. Called the Nano 16, this extruder is intended for the evaluation of samples in batches as small as 20 grams.

Figure 2: Micro-Plunger Feeder Mated to a Nano 16 Twin-Screw Extruder

Instead of the bilobed elements commonly used on larger machines, the Nano 16 employs trilobed screw elements to facilitate low-volume processing and mixing with the smaller OD/ID ratio.

Figure 3: Nano 16 Trilobal Screws

Figure 4: Micro 18 Bilobal TSE with 1.5/1 OD/ID

Figure 5: Nano 16 Trilobal TSE with 1.2/1 OD/ID

The same gearbox is used for the Nano 16 as for the larger Micro 18-GL Micro 18-mm HSEI twin-screw extruder. This design choice allows an 18-mm process section to be mated to the gearbox, providing a clear scale-up path to a 1.5/1 process section similar to those found on larger production machines.

One of the unique aspects of the Nano 16 is the way it simulates the starve-feeding mechanism normally used in production-scale twin-screw extrusion. Instead of conventional metering feeders, the Nano 16 uses a tiny patent-pending “micro-plunger” to meter small amounts of materials with nearly full utilization of the sample. This micro-plunger consists of a motor-driven piston within a stainless-steel tube that mates to the bottom of the Nano 16’s feed barrel.  A closed-loop Vector gearmotor drives the piston, allowing samples of 20 to 100 cc to be metered accurately into the barrel.

As with the starve-feeding mechanism on larger machines, the Nano 16 feed screw elements are designed to convey the materials at a higher rate than is being delivered by the micro-plunger. Thus, the combination of the Nano 16 twin-screw extruder and the micro-plunger feeder replicates the staging of unit operations and the shear-imparting mechanisms of production-scale twin-screw extrusion equipment.

Nano Extrusion Trials

To validate the Nano 16 design, a series of trials were performed to compound the pharmaceutical polymer hypromellose acetate succinate (HPMCAS) with 40% of a poorly soluble drug and a trace amount of an U.S. Food and Drug Administration (FDA)-approved blue color pigment. The objective was to demonstrate the viability of the extrusion process by using a very small sample with minimal waste. Also, the choice of a poorly soluble active ingredient was important because poor solubility is a barrier to usage for many new drugs.

All materials were premixed and metered by the Nano 16’s micro-plunger feeder. The trials used a 25:1 length/diameter process section, and the screw design included flighted, kneading, and shear-inducing elements.  An atmospheric vent and a low-volume strand die attachment were also part of the test system.

Tests were performed at feed rates of 2, 4, and 8 cc/min and under different run conditions. A feed rate of 2 cc/min translated to approximately 120 g/h, 4 cc/min to 240 g/h, and 8 cc/min to 480 g/h. The batch size selected for the premix was 50 grams, of which 44 grams of the sample was collected and usable for evaluation purposes. Approximately 6 grams of material was lost as follows: 1 gram at the extruder/plunger interface, 2 to 3 grams on the screws, and 2 grams in the die/front end.    Temperature profiles and screw rpm were selected on the basis of experience with similar formulations, and PC-based controls and data acquisition allowed for detailed analysis of the run conditions.

On the output end of the machine, the compounded material was cooled in an air-quenched annular chamber and cut into 1-mm pellets by a dual-drive strand pelletizer. The pellets then were milled into a powder and compressed into tablets for dissolution rate and solubility testing according to pharmaceutical standards.

The results (Figure 2) indicated the superiority of extrusion to process this poorly soluble active pharmaceutical ingredient compared with traditional “dry mixing” batch operations. The active ingredient was transformed from a crystalline to an amorphous structure during processing, and most of the drug was dissolved after 20 minutes. Without extrusion, this particular active ingredient might not have been a candidate for additional development.

Figure 6: Solubility Results from Dissolution Testing

Subsequent scalability tests were performed on larger extruders, including 2 kg/h runs on an 18-mm HSEI twin-screw and 6 kg/h runs on a model with 27-mm screws. Similar results were obtained on both larger machines, confirming the viability of the Nano 16 as an initial screening device.

In summary, traditional HSEI twin-screw extrusion technology has both similarities to and differences from the pharmaceutical mixing process. For most commodity products, the goal is to increase throughput rates. The discovery of cutting-edge drugs and advanced materials, however, requires machines that minimize the waste of costly developmental materials while providing an assessment of extrusion viability. With its new take on feeding and process section design, the 16-mm Nano meets both requirements.