Rotation of the screws creates distributive and dispersive mixing. Distributive mixing maximizes the division and
recombination of the materials while minimizing energy input by mixing with low extensional and planar-shear effects. This uniformly blends the materials but does not significantly reduce dispersed material particle size and yields minimal thermal and shear degradation of sensitive materials.
Dispersive mixing applies extensional and planar shear fields to break the dispersed materials to smaller size, ideally using energy at or slightly above the threshold level needed to break them down.
The use of different mixing elements allows the twin screw extruder
to perform both particle size reduction and mixing so that the APIs can be incorporated into
the polymer in dispersed form or, if the API
solubility in the polymer is high enough, in dissolved form. Since the extrudate cools rapidly on exiting the extruder, any API
that is dissolved in the polymer at the mixing temperature may be unable to recrystallize on cooling, leading to supersaturated solid solutions. In such cases stability of the product must be closely followed as recrystallization of the API
over long time-scales is possible, especially at elevated storage temperatures and high API
loadings, and may impact the shelf life of the final product.
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, designed to mix at low shear and pump at uniform pressures. Screws may be co-rotating (self-wiping), or counter rotating (calendar gap),with most extruders used for mixing being co-rotating.
Different types of exit dies are used to shape the extrudate to the desired profile. These dies include sheet and film dies used in transdermal film applications, strand dies used for medical tubing and some drug-eluting devices, shape dies used in blow moulding, and co-extrusion dies used in reservoir device designs. Different downstream auxiliary components are also used in the finishing process, including water baths and air
knives for cooling, conveyor belts for moving the extruded product from the die to the end of the line, strand-cutters for cutting the extrudate into tubing or rods, and spoolers for extrudate collection. Pelletizers are used for cutting the extrudate into smaller pieces for direct capsule
filling and in the case of some devices for injection molding to form the final product.
As with any dosage form, material selection is critical in the development of a successful product. For most applications, the polymer should be thermoplastic, stable at the temperatures used in the process, and chemically compatible with the API
during extrusion. For solid oral dosage forms, water soluble polymers are usually chosen from among polymers already used in pharmaceutical products such as poly(ethylene glycol) and poly(vinylpyrrolidinone). With the increased interest in using HME for pharmaceutical products, major polymer suppliers are also beginning to offer polymers specifically designed for pharmaceutical applications. For drug-eluting devices, the polymers are generally water-insoluble, and the majority of products under development use either ethylene vinyl acetate copolymers (EVAs) or polyurethanes.
allows the API
to be mixed with the polymer under the minimum of shear and thermal stresses and hence with the formation of minimal process-related API
degradants. Antioxidants are often included within the formulation, and the short residence time in the barrel (typically on the order of minutes) also helps to minimize thermal degradation especially compared to batch mixing and other compounding processes.
One strategy for controlling drug elution kinetics from devices such as intravaginal rings involves an extension of the simple extrusion technique. Simultaneous extrusion of a drug-loaded core strand with a release-controlling polymer sheath that encapsulates the core in a single
co-extrusion process produces a two-layer core-sheath strand. A specially designed extrusion head is fed
by two perpendicular extruders – one supplying the core composition, the other supplying the sheath material. The core-sheath strand is cut and the ends connected to make the final device.
HME provides product developers of medical devices, dissolving oral dosage forms and drug-eluting devices with a process option that maximizes API
mixing with polymer, while minimizing API
degradation, and even opens the door to products that cannot be prepared by other means.