(605g) Local Residence Time Distributions for Hot Melt Extrusion: Making a Black Box Concept Mechanistic | AIChE

(605g) Local Residence Time Distributions for Hot Melt Extrusion: Making a Black Box Concept Mechanistic


Bauer, H., Research Center Pharmaceutical Engineering
Khinast, J. G., Graz University of Technology
Local Residence Time Distributions for Hot Melt Extrusion: Making a black box concept mechanistic

Hannes Bauer*, Josip Matić*, Johannes Khinast*,**

*Research Centre Pharmaceutical Engineering GmbH, Inffeldgasse 13/III, 8010 Graz, Austria

**Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13/III, 8010 Graz, Austria

Email for correspondence: khinast@tugraz.at


Hot Melt Extrusion (HME) is a continuous manufacturing process used in the pharmaceutical industry to produce amorphous solid dispersions (or solutions) of poorly soluble active pharmaceutical ingredients (APIs). Process setup and scale-up are still a significant issues for the temperature and shear sensitive formulations used in the pharmaceutical industry.

Besides the high temperatures reached during the process, it is generally agreed upon that the Residence Time Distribution (RTD) significantly impacts the product properties. However, RTD theory was derived for ideal systems with uniform characteristics, such as plug flow reactors (PFR) or continuously stirred tanks (CSTRs). The characteristics in a Twin-Screw extruder vary considerably, along the screw axis, and across the screw cross section. Meaningful kinetic models which aim to predict product formation (or degradation) need to account for that.


Smoothed Particle Hydrodynamics1 (SPH) has an excellent track record in predicting the flow in extruder elements.2,3 The methods meshless nature allows for a convenient treatment of rotating moving boundaries such as extruder screws. In SPH the fluid consists of numerous flowing particles, which carry the fluid flow information. Therefore, the method is uniquely suited for in-silico tracer experiments. Such tracer experiments are useful for determining local RTDs in extruder screw elements. Three zones of similar behavior can be distinguished in the cross section of the elements: (1) high shear screw-barrel gap zone; (2) medium shear screw-screw intermeshing zone and (3) low shear screw channel zone. Following the trajectories of fluid elements we find them passing through these zones. Hence, we determine the local residence time in these zones as well as the number of transitions (number of passes) from one zone to the other.4,5


Instead of taking the classical black box point of view, which is usually associated with RTD models, we take a closer and more detailed look at twin-screw extruder elements. We derive local RTDs in the gap zone, the intermeshing region and the channel. We discuss the number of passes from one zone into another and we investigate how the total time the melt spends in a specific zone relates to the overall RTD. This approach is the basis for future mechanistic product property prediction of HME products.


  1. J. Monaghan, “Smoothed particle hydrodynamics,” Reports Prog. Phys., vol. 68, no. 8, pp. 1703–1759, Aug. 2005.
  2. Eitzlmayr and J. Khinast, “Co-rotating twin-screw extruders: Detailed analysis of conveying elements based on smoothed particle hydrodynamics. Part 1: Hydrodynamics,” Chem. Eng. Sci., vol. 134, pp. 880–886, 2015.
  3. Eitzlmayr, J. Matić, and J. Khinast, “Analysis of Flow and Mixing in Screw Elements of Corotating Twin-Screw Extruders via SPH,” AIChE J., 2017.
  4. Mann, U. , Rubinovitch, M. and Crosby, E. J. (1979), Characterization and analysis of continuous recycle systems. AIChE J., 25: 873-882.
  5. Mann, U. and Rubinovitch, M. (1981), Characterization and analysis of continuous recycle systems: Part II. Cascade. AIChE J., 27: 829-836.