A novel design for hot-melt extrusion pelletizers

Abstract In this work we investigated a novel die design for the scale-up of hot melt extrusion (HME) devices for direct pelletization of pharmaceutics. Therefore we analyzed the temperature distribution in a lab- and production-scale die as well as melt flow through the die. Finally we explored the possibilities of an inner rotating knife for stabilizing melt flow. The work was based on computational fluid dynamics for simulating non-Newtonian melt flow and corresponding temperature fields. The results show that a tight temperature control of the die material is necessary to guarantee a safe scale-up of the process. Even in lab-scale applications temperature inhomogeneities have been observed both experimentally as well as in the simulation. These inhomogeneities act as an trigger to destabilize melt flow and hence could lead to a shutdown of the process. The proposed inner rotating knife acts as a pulsating device and consequently is able to enhance process stability. However, due to heat dissipation in the small gap between rotor and stator, this device has to be fitted with a separate low-speed drive and cannot be coupled directly to the main extruder shaft.

[1]  Conjugate thermal transport in the channel of an extruder for non-newtonian fluids , 1998 .

[2]  J.F.T. Pittman,et al.  Thermal Effects in Extrusion: Slit Dies , 1994 .

[3]  den Cfj Jaap Doelder,et al.  Onset of the sharkskin phenomenon in polymer extrusion , 1998 .

[4]  Milivoje M. Kostic,et al.  Design of Extrusion Dies , 2006 .

[5]  G. Böhme,et al.  Strömungsmechanik nichtnewtonscher Fluide , 2000 .

[6]  Eric Doelker,et al.  Various ways of modulating the release of diltiazem hydrochloride from hot-melt extruded sustained release pellets prepared using polymeric materials , 1995 .

[7]  Jean-Robert Clermont,et al.  Numerical simulations of non-isothermal three-dimensional flows in an extruder by a finite-volume method , 2005 .

[8]  J. Staniforth,et al.  The effect of molecular weight on the rheological and tensile properties of poly(ϵ-caprolactone) , 1996 .

[9]  E. Doelker,et al.  Processing of Polymeric Dosage Forms for Advanced Drug Delivery: From Melt-Extrudates to Nanoparticles , 2005 .

[10]  Michael A Repka,et al.  The influence of guaifenesin and ketoprofen on the properties of hot-melt extruded polyethylene oxide films. , 2004, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[11]  K. Hornung,et al.  A simple geometrical solution to the surface fracturing problem in extrusion processes , 2001 .

[12]  Charles E. Martin,et al.  Pharmaceutical Extrusion Technology , 2003 .

[13]  S. Brun,et al.  The Tablet Formulation of Lopinavir/Ritonavir Provides Similar Bioavailability to the Soft-Gelatin Capsule Formulation With Less Pharmacokinetic Variability and Diminished Food Effect , 2007, Journal of acquired immune deficiency syndromes.

[14]  James W McGinity,et al.  Production of spherical pellets by a hot-melt extrusion and spheronization process. , 2002, International journal of pharmaceutics.

[15]  M. F. Tomé,et al.  Die-swell, splashing drop and a numerical technique for solving the Oldroyd B model for axisymmetric free surface flows , 2007 .

[16]  Eric Doelker,et al.  Evaluation of hot-melt extrusion as a new technique for the production of polymer-based pellets for sustained release capsules containing high loadings of freely soluble drugs , 1994 .

[17]  Wei Yang,et al.  Hot-melt extrusion for enhanced delivery of drug particles. , 2007, Journal of pharmaceutical sciences.

[18]  J. Breitenbach Melt extrusion: from process to drug delivery technology. , 2002, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[19]  Charles E. Martin,et al.  Pharmaceutical Applications of Hot-Melt Extrusion: Part I , 2007, Drug development and industrial pharmacy.

[20]  Philippe A. Tanguy,et al.  Adaptive finite element simulations of fluid flow in twin-screw extruders , 2003, Comput. Chem. Eng..

[21]  João M. Nóbrega,et al.  Computer aided rheological design of extrusion dies for profiles , 2001 .

[22]  R. Chokshi,et al.  Characterization of physico-mechanical properties of indomethacin and polymers to assess their suitability for hot-melt extrusion processs as a means to manufacture solid dispersion/solution. , 2005, Journal of pharmaceutical sciences.

[23]  José A. Covas,et al.  On-line monitoring of the residence time distribution along a kneading block of a twin-screw extruder , 2004 .

[24]  Antoine Rouilly,et al.  Thermo-mechanical processing of sugar beet pulp. II. Thermal and rheological properties of thermoplastic SBP , 2006 .

[25]  K. Migler,et al.  Extensional deformation, cohesive failure, and boundary conditions during sharkskin melt fracture , 2002 .