(178e) Modeling Hot-Melt Extrusion Pelletizers

Hot-melt extrusion (HME) is one of the key processes for a continuous production of high-quality pharmaceuticals. Products manufactured by means of HME have significant advantages over conventional drug delivery systems. HME has the benefit to be a solvent free, environmental friendly and cost efficient technology. Furthermore, HME dosage forms have superior drug delivery properties due to the formation of solid dispersions and solid solutions. This is relevant for poorly-soluble pharmaceutically active substances, frequently encountered among novel drugs. Due to this advantages HME technology has been applied to a wide range of dosage forms ranging from granules over transdermal systems to implants.^1-3 However, reliable scale-up of HME technology is still a major challenge and a breakthrough has not been achieved yet. This is mainly due to a limited insight into the process.

In our work we explore the scale-up of hot melt extrusion (HME) devices for direct pelletization of pharmaceuticals by means of computational fluid dynamics (CFD). HME with direct pelletization is a novel concept where the extruded material is cut into small pellets directly after exiting the extrusion die. We investigate non-isothermal, non-Newtonian flow of the melt through different die geometries via a detailed CFD model. To get a refined picture of melt flow through the device, we also take the temperature distribution in the die material into account. In our work we explore different possibilities for stabilizing melt flow including rotating internals.

The results show that a tight temperature control of the die material is necessary to guarantee continuous melt flow. Temperature inhomogeneities using a conventional die design have been identified via simulations. These inhomogeneities act as a trigger to destabilize melt flow and hence lead to a shutdown of the process. We show that a significant improvement in process reliability can be obtained when using an optimized die design. Finally, we highlight some aspects of pellet formation in this novel HME pelletization process.

(1) Breitenbach J. Melt extrusion: from process to drug delivery technology. European Journal of Pharmaceutics and Biopharmaceutics. 2002;54:107-117.

(2) Crowley MM, Zhang F, Repka MA, Thumma S, Upadhye SB, Battu SK et al. Pharmaceutical applications of hot-melt extrusion: Part I. Drug Development and Industrial Pharmacy. 2007;33:909-926.

(3) Miller DA, McConville JT, Yang W, Williams RO, McGinity JW. Hot-melt extrusion for enhanced delivery of drug particles. Journal of Pharmaceutical Sciences. 2007;96:361-376.