Continuous Mixing of Solid Dosage Forms via Hot-Melt Extrusion - Pharmaceutical Technology

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Continuous Mixing of Solid Dosage Forms via Hot-Melt Extrusion
The author describes the benefits, processes, and practicality of using hot-melt extrusion to mix active pharmaceutical ingredients with pharmaceutical-grade polymers.

Pharmaceutical Technology
Volume 32, Issue 10, pp. 76-86

Figure 4 (All figures are courtesy of the author.)
Screw designs can be shear-intensive and/or shear-passive with compounding efficiencies defined in terms of dispersive and distributive mixing. In dispersive mixing, the particles are broken down. Dispersive mixing elements result in the materials experiencing extensional- and planar-shear effects. In distributive mixing, the materials are uniformly blended but not broken down. Distributive mixing elements force high-melt division rates with significantly less extensional and planar-shear effects. Distributive mixing is often implemented for mixing heat- and shear-sensitive APIs with minimal degradation (see Figure 4).

Figure 5 (All figures are courtesy of the author.)
The cross-section of the barrel for a twin-screw extruder is characterized by a barrel opening in the shape of a "figure 8." Barrels for twin-screw extruders can be either one-piece or modular and can be configured for downstream feeding and venting. Barrel sections are heated by electric heaters or liquid. Barrel-cooling facilitates a temperature set point to maintain the desired melt viscosity within the process section. Extruder barrel(s) are typically cooled by liquid, and sometimes air. The most effective heat-transfer design uses axial cooling bores inside the barrel and close to the process melt stream (see Figure 5).

The segmented design of the process section enables specific screw and barrel geometries to be matched in a calculated and iterative manner to the unit operations that are performed in the process section. Modularity also makes the twin-screw extruder a flexible and powerful research tool when developing new applications for dosage forms.

Twin-screw extruder types

There are two distinct families of twin-screw extruders: high-speed energy input (HSEI) twin-screw extruders, which run up to more than 1200 rpm; and low-speed late fusion (LSLF) twin-screw extruders, which run up to 50 rpm. HSEI twin-screw extruders are primarily used for compounding, reactive processing and/or devolatilization. By contrast, LSLF counterrotating twin-screw extruders are designed to mix at low shear and pump at uniform pressures but are often inadequate to perform energy-intensive processing.

HSEI twin-screw extruders. HSEI twin-screw extruders are mass-transfer devices used for intensive mass-transfer operations such as compounding, devolatilization, and reactive extrusion. HSEI twin-screw extruders are available in co-rotation and counterrotation and have top-end screw speeds from 300 to more than 1200 screw rpm.

HSEI twin-screw extruders are starve-fed with the output rate determined by the feeder(s). The extruder-screw rpm is independent from the feed rate and is used to optimize compounding efficiencies. Because the pressure gradient is controlled and remains at zero for much of the process, materials can be introduced into downstream barrel sections, typically by a twin-screw side stuffer that "pushes" materials into the extruder screws. Downstream introduction of heat- or shear-sensitive APIs can be particularly beneficial to avoid high-shear regions and minimize residence time exposure. The controlled pressure profile also facilitates venting.

Figure 6 (All figures are courtesy of the author.)
For a co-rotating twin-screw extruder, the screws are termed "self-wiping," as the opposing surface velocities in the intermesh regions cause the material to follow a figure 8 pattern. In co-rotation, the rotational clearances typically limit the lobe count to two for standard flight depths (see Figure 6).


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