(648c) Die Face Pelletizing of Sticky HME Formulations

Hot melt extrusion is a continuous process with growing importance for the pharmaceutical industry [1]. An extruder processes raw materials into homogeneous strands of molten material and offers, in that way, robust production opportunities for solid dispersions. Solid dispersions are required to face current drug development challenges such as poor water solubility or modified release of the active pharmaceutical ingredient (API).

The molten material is shaped in the downstream process into the product of the extrusion line. Often, pellets are needed as intermediates for tablet compaction, capsule filling or injection molding. Pellets can be produced by die face pelletizing or strand pelletizing. The pelletizing methods distinguish themselves in terms of material temperature where the cutting takes place. In strand pelletizing the emerging material is drawn as cylindrical strands from the extrusion die. It runs through a cooling section and is chilled near or below the softening point and cut by a knife roller. Thus, solid bodies are cut resulting in cylindrical‑shaped pellets. In contrast, die face pelletizing is executed with a rotating knife pressed on the extrusion die plate. Thus, the material is in a viscous state during cutting and can deform due to surface tension into spherical pellets [2], [3]. Spherical pellets lead to better flowability and enhance dosing accuracy in subsequent handling steps. In addition, the pellets are conveyed with a cooling air stream to the product container where they are separated from the air stream, e.g. with an impact separator. This arrangement results in a simple self-contained construction and offers high spatial flexibility. However,  air cooled die face pelletizing was limited to few formulations because of stickiness [4], although the plastics industry uses a similar principle to process sticky materials for several decades. The plastics industry uses underwater pelletizing systems, where the melt stickiness is prevented by higher cooling intensities. However, water-cooled systems are not suitable in the pharmaceutical field due to water solubility of the API and high purity requirements.

The aim of the presented study was a comprehensive understanding of polymer melt stickiness and its avoidance during die face pelletizing. The influence of heat transfer on adhesion properties has been investigated and a hypothesis on melt stickiness proposed. The hypothesis relates heat transfer properties to the materials phase transition temperature. The proposed hypothesis is supported with probe tack investigations at defined heat transfer conditions. This realization triggered a novel die plate design, which thermally decouples the die face from the melt flow channel. Thus, the surface temperatures of the pelletizer are low as compared to underwater pelletizing so that stickiness is suppressed. The novel die plate’s heat balance has been calculated and optimized in-silico and subsequently built and tested as a real prototype.

The prototype was incorporated into an extrusion line consisting of an 18 mm twin-screw extruder (Coperion ZSK 18) and a die face pelletizer (Automatik Plastics Machinery GmbH, Sphero^®-THA). The setup has successfully been applied to manufacture pellets from different sticky pharmaceutical polymers (e.g. copovidone). The obtained pellets are almost spherical and in the size range of 1 mm. Thus, it has been proven that the new design enables processing of sticky materials so that a broader range of formulations can benefit from the advantages of die face pelletizing.

References:

[1] M. A. Repka, N. Langley, and J. DiNunzio, Eds., Melt Extrusion - Materials, Technology and Drug Product Design. New York, Heidelberg, Dordrecht, London: Springer, 2013.

[2] E. Roblegg, E. Jäger, A. Hodzic, G. Koscher, S. Mohr, A. Zimmer, and J. Khinast, “Development of sustained-release lipophilic calcium stearate pellets via hot melt extrusion.,” Eur. J. Pharm. Biopharm., vol. 79, no. 3, pp. 635–645, Nov. 2011.

[3] S. Bialleck, “Herstellung von Polysaccharidpellets mittels Schmelzextrusion,” Rheinischen Friedrich-Wilhelms-Universität Bonn, 2011.

[4] D. Treffer, P. Wahl, D. Markl, G. Koscher, E. Roblegg, and J. Khinast, “Hot Melt Extrusion as a Continuous Pharmaceutical Manufacturing Process,” in Melt Extrusion: Equipment and Pharmaceutical Applications, M. Repka, Ed. Springer Publishers, 2013.