(586l) Implementation of a Novel Inline Particle Size Measurement Tool to Monitor Pellets Produced By Hot Melt Extrusion and Die Face Pelletizing

Hot melt extrusion is a promising manufacturing opportunity to increase the water solubility of poor water soluble drugs. The increase is obtained by the formation of various different types of solid dispersion. The extruder produces homogeneous molten material, which is mostly processed to intermediate products such as pellets or powders. Pellets are often desired for the downstreaming into the final drug product, e.g. capsule filling, tablet compaction, injection molding, due to excellent flowability and content uniformity. Cold strand cutters are commonly used for their production. The aim of our work is the establishment of hot die face cutting as production technology in the pharmaceutical industry. The advantage of this technology is that almost spherical pellets can be obtained with suitable formulation and process parameters [2],[3]. The pellet formation process is a complex relation of rheology, cooling intensity, extrusion speed, die geometry, knife design and speed. Therefore, an inline particle monitoring system is a powerful tool for process development as well as monitoring of the production process.

The experimental setup comprises of the processing and the monitoring equipment. The processing equipment consists of a co-rotating twin screw extruder ZSK 18 (Coperion, Germany) equipped with KT20 loss in weight feeders (KTron, Switzerland) and a hot die-face pelletizer (Automatik Plastics Machinery GmbH, Germany). The novel Eyecon™ (Innopharma labs, Ireland) was used for inline monitoring of the particle properties. Reference particle analysis was performed with a QICPIC System (Sympatec, Germany).

The Eyecon™ camera is a method based on diffuse light and uses three different light sources, which are circular arranged around the lens. This special illumination methods allows to derive three dimensional information from a two dimensional image. This additional information is used for improved particle edge detection, especially by overlapping particles. In this work different implementation approaches to the pelletizing line are investigated. Encountered problems are discussed and solutions provided. The best implementation approach was chosen for a comparison with the reference method and showed good agreement. In addition, it was recognized that the color images are useful to obtain information about the surface morphology of the produced pellets.

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