(402a) Continuous Pharmaceutical Hot-Melt Extrusion and Hot-Die Face Pelletizing

The pharmaceutical industry goes through a paradigm change. So far batch manufacturing was nearly the only way to produce pharmaceuticals. A new approach, however, is continuous manufacturing. Hot melt extrusion (HME) is such a continuous process with significant potential for the manufacturing of different dosage forms with an improved control of the drug release profile^1,2. HME produces homogeneous strands of molten material, which are further processed in a downstream process. A hot die-face pelletizer is one possible downstream option. It cuts the strands directly at the die plate into pellets. Some authors reported that spherical pellets can be obtained directly with a hot die-face pelletizer³. The benefit of spherical pellets is better flowability compared to non-spherical pellets, which is an important requirement for further particle processes. In this work the application of a hot die-face pelletizer as a continuous downstream process is demonstrated.

The experimental setup consists of a co-rotating twin screw extruder ZSK 18 (Coperion, Germany) and a hot die-face pelletizer (Automatik Plastics Machinery GmbH, Germany). Powders or pellets consisting of active pharmaceutical ingredient (API) and excipients are fed continuously to the intake zone of the extruder with loss-in-weight feeders (K-Tron, Switzerland). The extruder itself combines several unit operations, such as conveying, mixing, melting, and degassing within one apparatus. At the extruder outlet the molten material is pushed through an extrusion die and homogeneous strands emerge from the die plate. The strands are cut continuously into pellets with rotating knifes directly at the die plate. An airstream cools the strands before the cutting as wells as the particles after the cutting process. Furthermore, it conveys the particles to the next processing step. In order to ensure good particle qualities the particle size and shape is monitored in-line with the Eyecon (Innopharma Labs, Ireland). Most process parameters are collected with SIPAT (Siemens, Belgium) which enables an efficient process development and monitoring.

Several pharmaceutical polymers and formulations have been investigated for hot die face pelletizing. Not all formulations are suitable for this downstream process. Rheological investigations of the formulations have been performed and approaches to predict applicability of the hot die-face pelletizer are derived.

References:

1. Breitenbach J.: Melt extrusion: from process to drug delivery technology, European Journal of Pharmaceutics and Biopharmaceutics 2002, 54, 107-117.
2. Roblegg E, et. al.: Development of sustained-release lipophilic calcium stearate pellets via hot melt extrusion, European Journal of Pharmaceutics and Biopharmaceutics 2011, 79, 635-645.
3. Bailleck S; Rein H, Preparation of starch-based pellets by hot-melt extrusion, European Journal of Pharmaceutics and Biopharmaceutics, 2011, 79, 440-448