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 7 (All figures are courtesy of the author.)
In counterrotation, the surface velocities of the screws in the intermesh region work in the same direction which results in materials being forced between the screws where extensional mixing occurs, referred to as the calendar gap. Geometric characteristics inherent with counterrotating screw designs makes it possible to have up to six lobes at the same flight depth as bilobal co-rotating designs, which results in more mixing events for each screw rotation (see Figures 7 and 8).

Figure 8 (All figures are courtesy of the author.)
LSLF twin-screw extruders. The LSLF counterrotating, intermeshing twin-screw extruder is designed for gentle melting and mixing combined with a narrow residence distribution and high-pressure generation capabilities. The screw flights converge in the same direction in the nip region, causing the gap between the flights to be small and minimizing leakage from one screw channel to the next. Mixing occurs between the screws as the material experiences shear effects in the calendar gap. This device can be used for shear- or temperature-sensitive materials that do not require intensive mixing.

Generic twin-screw extrusion related formulas

Shear rate. Shear forces result in mixing, which is the primary function of most HSEI twin-screw extruders. Shear rate describes the velocity gradient between two surfaces moving at different speeds. For a HSEI twin-screw extruder, this is a function of screw outside diameter, screw speed, and overflight gap.

The following formula is relevant:

Peak shear rate = (π D n)/(h 60)

in which D is the screw diameter, n is the screw speed in rpm, and h is the overflight clearance. So for a HSEI twin-screw extruder with 27 mm OD screws and an overflight gap of 0.1 mm operating at 600 rpm, the following applies:

Peak shear rate = (π 27 600)/(0.1 60) = 8478/s-1

This equation does not take into account extensional shear, an important component for dispersive mixing but does provide a usable benchmark for comparison and troubleshooting purposes.

Shear stress. The magnitude of the applied stress that the materials experience is a function of the shear rate and viscosity, and is reflected by this formula:

Shear stress = Viscosity (Ec) Shear rate

Barrel temperatures are used to manage the viscosity of the melt, which impacts the mixing quality. Cooling is often used to raise the viscosity (Ec), which facilitates dispersive mixing in a HSEI twin-screw extruder. A smaller Ec is preferred if distributive mixing is the goal.

Specific energy. Specific energy (SE) is the amount of power that is being input by the motor into each kilogram of material being processed. This is calculated in two steps:

Applied power:

kw (applied) = kw (motor rating) % torque rpm running/max. rpm x 0.97 (gearbox efficiency)


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