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 1 (All figures are courtesy of the author.)
Twin-screw extruder process materials are bound by screw flights and barrel walls (see Figure 1). Rotating screws, driven by a motor, impart shear and energy into the materials being processed. Inside any extruder, a number of process tasks are performed such as feeding, melting, mixing, venting, and developing die and localized pressure. Control parameters include screw speed (rpm), feed rate, process-section temperatures, and vacuum level (for venting). Typical parameters that are monitored include melt pressure, melt temperature, and motor amperage (torque). In-line optical sensors can be used to monitor the quality of the melt stream.

Programmable logic controllers (PLC), in combination with various control software packages, are specified to fulfill FDA 21 CFR Part 11 regulations. These database packages offer sophisticated security and backup features that meet the intent of this regulation.

Figure 2 (All figures are courtesy of the author.)
A common extrusion term is "length to diameter ratio" or L/D. This term expresses the length of the screw divided by the diameter. For instance, an extruder that is 1000 mm long with a 25 mm screw diameter has a 40:1 L/D. Typical extrusion process lengths are in the 20 to 40:1 L/D range, or longer. Extruder residence times are generally between 5 s and 2 min, depending upon the type of extruder, L/D, and how the extruder is operated with regard to feed rate and screw rpm (see Figure 2).

Another common term is "outside diameter of the screw" or OD. For instance, when referring to a 20 mm extruder, OD refers to the outer diameter of each screw for a twin-screw extruder. The inside diameter, or ID, is the OD less the flight depth multipled by two.

The flight depth of the screws is an important design parameter. A deeper flight depth increases the free volume in the machine but limits the torque transmittal.

Figure 3 (All figures are courtesy of the author.)
Finding the optimum balance between free volume and torque is important because the balance directly impacts attainable throughput rates (high or low), as well as the energy that is imparted into the materials. Twin-screw extruders can process as little as a 20-g batch and more than 5000 kgs/hr.

The screws are the heart of any twin-screw extruder and the design directly impacts the quality of the dosage form. Screw elements are flighted for material transport, and nonflighted to create shear regions for melting or mixing. Solids conveying and melting occurs early in the process section. Screw elements for mixing and devolatilization are applied as required. Discharge elements then build and stabilize pressure before discharge. Screws are typically segmented and assembled on splined shafts. One-piece construction is also possible for improved cleaning and validation purposes.


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