Hot-melt extrusion: an emerging drug delivery technology

Jan 01, 2009

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Hot-melt extrusion (HME) is an established process that has been used since the early 1930s, predominately in the plastics manufacturing industry, but also in the food processing industry. Currently, more than half of all plastic products, including bags, sheets, and pipes, are manufactured using HME.1 Since the advent of plastics production, polymers have been melted and formed to different shapes for a variety of industrial and domestic applications. Extrusion can be simply defined as the process of forming a new material (the extrudate) by forcing it through an orifice or die under controlled conditions,2 such as temperature, mixing, feed-rate and pressure.

The HME process

At the most fundamental level, an extruder consists of a platform that supports a drive system, an extrusion barrel, a rotating screw arranged on a screw shaft and an extrusion die for defining product shape. Typically, process parameters are controlled via connection to a central electronic control unit. The extrusion drive system generally comprises motor, gearbox, linkage and thrust bearings, whereas the barrel and screw is commonly utilized in a modular configuration.3 Simple single screw arrangements consist of only a single rotating screw inside a stationary extruder barrel, whereas more advanced machines involve twin-screw systems utilizing either a corotating or counter-rotating screw configuration. It is common for the extrusion screw to be characterized by the length/diameter (L/D) ratio, which typically ranges from 20 to 40:1. Typical pilot plant extruders have diameters ranging 18–30 mm, whereas production machines are much larger with diameters typically exceeding 50 mm. Irrespective of the complexity of the machine, the extruder must be capable of rotating the screw(s) at a selected speed while compensating for the torque generated from the material being extruded.

Figure 1
A simple single screw extrusion system comprises one rotating screw inside a stationary barrel that may be conveniently subdivided into three distinct zones: feed zone, compression zone and metering zone. The depth and/or pitch of the screw flights differ within each zone, generating variable pressure along the screw length (zone dependent). Because of the large screw flight depth and pitch, the pressure within the feed zone is very low, allowing for consistent feeding from the hopper and gentle mixing of API and excipients (Figure 1). The primary function of the subsequent compression zone is to melt, homogenize and compress the extrudate so that it reaches the metering zone in a form suitable for extrusion. Consequently, the compression zone must impart a high degree of mixing and compression to the material. This is achieved by decreasing the screw pitch and/or the flight depth, resulting in a gradual increase in pressure along the length of the compression zone.4 The final section, the metering zone stabilizes the pulsating flow of the matrix, thus ensuring the extruded product has a uniform thickness. Constant screw flight depth and pitch helps maintain continuous high pressure to ensure a uniform delivery rate of molten material through the extrusion die and, hence, a uniform product.

At a minimum, a screw extruder consists of three distinct parts:

  • a conveying system for material transport and mixing
  • a die system for forming
  • downstream auxiliary equipment for cooling, cutting and/or collecting the finished product.

Individual components within the extruder are the feed hopper, temperature controlled barrel, rotating screw, a die and heating/cooling elements. Additional systems include mass flow feeders to accurately meter materials into the feed hopper, PAT to measure extrudate properties (near infra red systems and laser systems), liquid and solid side stuffers, vacuum pumps for degassing, pelletizers and calendaring equipment. Standard process control and monitoring devices include zone temperature and screw speed with optional monitoring of torque, drive amperage, melt pressure and melt viscosity. Temperatures are normally controlled by electrical heating bands and monitored by thermocouples.