Hot-melt extrusion is a recognized process for the manufacture of solid dispersions and innovative new dosage forms. It is
an established process that has been used in the plastics and food industries since the 1930s. In the 1980s, BASF SE was the
first to apply the melt extrusion process based on polymers with high glass transition temperatures (such as polyvinylpyrrolidones)
to pharmaceuticals (2).
Extruders for pharmaceutical use have been designed and adapted for mixing drugs with carriers in various dosage forms. The
significant difference between extruders for thermoplastics and pharmaceutical applications is the equipment used, and hence,
the contact surface, which must meet regulatory requirements. The contact parts of the extruders used in pharmaceuticals must
not be reactive nor may they release components into the product. The extruder equipment is specially configured to fulfill
all cleaning and validation standards applicable to the pharmaceutical industry.
The use of extruders in the pharmaceutical industry cannot be seen as a niche application. Figure 5 demonstrates four fields
of versatility of the technology. Not all the benefits available, however, have been realized to date.
Figure 5: The four fields of versatility of hot-melt extrusion technology in the pharmaceutical industry.
In principle, an extruder consists of barrels enclosing single or twin screws that transport and, subsequently, force the
melt through a die, giving it a particular shape. The barrel can be heated to the desired temperature. Due to the external
heat and shear provided by the screws, the polymer is plasticized and its viscosity reduced. Hot-melt extrusion is a typical
continuous process, because the extruder is fed at one side and the extruded material exits from the other side. This makes
it even more attractive for pharmaceuticals (3). The hot-melt extrusion process comprises the steps melting, mixing and shaping.
Advantages of hot-melt extrusion in detail
Within the pharmaceutical industry, hot-melt extrusion has been used for various purposes, such as:
- Enhancing the dissolution rate and bioavailability of a drug
- Controlling or modifying drug release
- Taste masking
- Stabilizing the API
- Parenteral depots and topical delivery systems.
Once developed, hot-melt extrusion is a reliable and robust process offering benefits in cost-efficiency. Compared to other
processes for the production of solid solutions, it is far less complex, because the manufacturing of such dosage forms requires
only a few steps and avoids the use of organic solvents (Figure 6).
Figure 6: From poor API solubility to a final formulation.
Hot-melt extrusion also has advantages over solvent-based methods of forming solid solution and dispersions (Figure 7):
Figure 7: Opportunities and advantages of hot-melt extrusion.
- No need to handle explosive solvents
- Absence of residual solvents
- Continuous processing possible
- Possibility of continuous processing
- Fewer process steps
- High product density
- Non-dusty pellets (e.g., for highly active ingredients formulations)
- Small-scale equipment
- Non-aqueous process.