Hot melt extrusion (HME) is the process of continuously applying heat and pressure to melt a polymer and forcing it through an orifice. The hot melt extrusion process is well-known, developed to produce polymer products of uniform shape and density, and its industrial application dates back to the 1930s. It is one of the most widely applied processing technologies in the plastic, rubber, and food industries and is used to prepare more than half of all plastic products including bags, films, sheets, tubes, fibers, foams, and pipes. HME has more recently been applied to the healthcare industry where it is used to manufacture medical devices and mix active pharmaceutical ingredients (APIs) with polymers. The hot melt extrusion process is used to enhance the API’s bioavailability or prepare precursors for thermoplastic drug-eluting devices, such as subcutaneous and intraocular implants and intravaginal rings. This technical brief discusses the equipment and principles of HME with an emphasis on its use in the pharmaceutical industry.

The HME process is shown schematically in Figure 1

HME is carried out using an extruder – a barrel containing one or two rotating screws that transport material down the barrel. Extruders consist of four distinct parts:

An opening through which material enters the barrel, which may have a hopper filled with the material(s) to be extruded or be continuously supplied in a controlled manner by one or more external feeder(s).

A conveying (process) section, which comprises the barrel and the screw(s) that transport and, where applicable, mix the ma

An orifice (die) for shaping the material as it leaves the

Downstream auxiliary equipment for cooling, cutting, and/or collecting the finished

Melting happens due to frictional heating inside the barrel. In twin-screw extruders, materials shear between the screws and the barrel wall. The barrel is heated with heaters or cooled with water. Temperatures are optimized to keep material viscosity low for mixing and movement, avoiding thermal degradation.

Twin screw extruder screws are engineered for different mixing and conveying conditions in the barrel. During development, modular screws with multiple elements on a common shaft allow tailored designs. Screw sections can reduce particle size, mix, and convey materials. The L/D ratio (length to diameter) optimizes mixing and zone number for the final product. Figure 4 shows a complete modular screw. Single-piece production screws can match development designs and are easier to clean for cGMP compliance.

There are two families of twin screw extruders: high-speed energy input (HSEI) twin-screw extruders, which are primarily used for compounding, reactive processing, and/or devolatilization, and low-speed late fusion (LSLF) twin-screw extruders, which are designed to mix at low shear and pump at uniform pressures. Screws may be co-rotating (self-wiping), which is the most popular, or counter-rotating (calendar gap). See Figure 6.

Material selection is crucial for a successful product. Polymers should be thermoplastic, stable at process temperatures, and chemically compatible with the API. For solid oral dosage forms, water-soluble polymers like poly(ethylene glycol) and poly(vinylpyrrolidinone) are common. With growing interest in HME for pharmaceuticals, suppliers offer polymers specifically designed for these applications. Drug-eluting devices generally use water-insoluble polymers, such as ethylene vinyl acetate copolymers (EVAs) or polyurethanes.

Hot melt extrusion process mixes the API with the polymer with minimal shear and thermal stress, reducing API degradants. Antioxidants are often added, and the short residence time in the barrel (minutes) minimizes thermal degradation, especially compared to batch mixing.

One strategy to control drug elution from devices like intravaginal rings extends simple extrusion. Co-extrusion of a drug-loaded core with a release-controlling polymer sheath forms a two-layer core-sheath strand. A special extrusion head, fed by two perpendicular extruders, supplies the core and sheath materials. The core-sheath strand is cut and ends are connected to create the final device.

Hot melt extrusion processoffers product developers a processing option that maximizes API mixing while minimizing degradation, enabling innovative medical devices, dissolving oral dosage forms, and drug-eluting devices.

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