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Licensed Unlicensed Requires Authentication Published by De Gruyter November 4, 2014

Viscosity Analysis of a Polymer-Based Drug Delivery System Using Open-Source CFD Methods and High-Pressure Capillary Rheometry

H. R. Juster, T. Distlbacher and G. Steinbichler

Abstract

In this study the viscosity behavior of the polymer-based drug delivery system (Soluplus-Fenofibrate) at high shear rates was investigated using (i) Computational Fluid Dynamics (CFD) methods and (ii) experimental data acquired with a high-pressure capillary rheometer. The barrel and capillary were rebuilt in the virtual domain by means of finite-volume methods and used for fluid dynamic simulations. Our primary focus was on validating the Carreau-Winter and Yasuda material models in the Open Field Operation and Manipulation program (OpenFOAM) and investigating their usefulness in this type of simulation.

First, the models were fitted to experimental data from a well-known system – polystyrene type (145D, BASF). The results showed that the Yasuda model fit must be applied to obtain the correct material properties when simulating a non-Newtonian melt flow in a wide range of shear rates. The Carreau-Winter model was found to be valid only in the zero shear-rate viscosity region. On the basis of these findings, the Soluplus-Fenofibrate system was subsequently characterized and simulated. We observed that Fenofibrate (lipid-regulating agent) acts as a plasticizer in this polymer system and decreases system viscosity at lower shear rates compared to pure the Soluplus (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) at the same temperatures.

Our results show that the viscosity models can be implemented accurately even for processes with high shear rates, which also involve high temperatures.


* Mail address: Herwig, Rainer Juster, Institute of Polymer Science, Johannes Kepler University, A-4040 Linz. E-mail:

References

Bagley, E. B., “End Correction in the Capillary Flows of Polyethylene”, Journal of Applied Physics, 2, 624627 (1957)10.1063/1.1722814Search in Google Scholar

Breitenbach, J., “Melt Extrusion: From Process to Drug Delivery Technology”, Eur. J. Pharm. Biopharm., 54, 107117 (2002)10.1016/S0939-6411(02)00061-9Search in Google Scholar

Butler, J. M., Dressman, J. B., “The Developability Classification System: Application of Biopharmaceutics Concepts to Formulation Development”, J. Pharm. Sci., 99, 49404954 (2010)10.1002/jps.22217Search in Google Scholar

CAMPUSPlastics, http://www.campusplastics.com, M-Base Engineering + Software GmbH, Aachen, Germany (2013)Search in Google Scholar

Carreau, P. J.: Rheological Equations from Molecular Network, PhD Thesis, University of Wisconsin, Madison, USA (1968)Search in Google Scholar

Carreau, P. J., “Rheological Equations from Molecular Network Theories”, Rheol. Acta, 16, 99128 (1972)Search in Google Scholar

Carreau, P. J., De Kee, D. C. R., and Chhabra, R. P.: Rheology of Polymeric Systems, Hanser Gardner Publications, Munich (1997)Search in Google Scholar

Chokshi, R. J., Sandhu, H. K., Iyer, R. M., Shah, N. H., Malick, A. W. and Zia, H., “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”, J. Pharm. Sci., 94, 24632474 (2005)10.1002/jps.20385Search in Google Scholar

Dhirendra, K., et al., “Solid Dispersions: A Review”, Pakistan Journal of Pharmaceutical Sciences, 22, 234246 (2009)Search in Google Scholar

Eggenreich, K., Schrank, S., Koscher, G., Treffer, D., Roblegg, E. and Khinast, J. G., “Injection Molding as a One-Stop-Production to Produce Pharmaceutical Dosage Forms”, AlChE Annual Meeting (2013)Search in Google Scholar

Ferziger, J. H., Peric, M.: Computational Methods for Fluid Dynamics, Springer, Berlin, Heidelberg (2002)10.1007/978-3-642-56026-2Search in Google Scholar

Göttfert, WinRheo II manual, Göttfert Werkstoff-Prüfmaschinen GmbH, Buchen, Germany (2012)Search in Google Scholar

Kolter, K., Karl, M., and Gryczke, A.: Hot-Melt Extrusion with BASF Pharma Polymers, Extrusion Compendium, 3rd Edition, BASF SE, Ludwighafen, Germany (2012)Search in Google Scholar

Lipinski, C. A., “Avoiding Investment in Doomed Drugs, Is Poor Solubility an Industry Wide Problem?”, Curr. Drug. Dis., 5, 1719 (2001)Search in Google Scholar

Miller-Chou, B. A., Koenig, J. L., “A Review of Polymer Dissolution”, Prog. Polym. Sci., 28, 12231270 (2002)10.1016/S0079-6700(03)00045-5Search in Google Scholar

OpenCFD Ltd., S., “Openfoam Source Code”, http://www.openfoam.com, accessed 01.07.2013 (2013)Search in Google Scholar

Patankar, S.H.: Numerical Heat Transfer and Fluid Flow, Hemisphere Publishing Corp., Washington (1980)Search in Google Scholar

Schwarze, R.: CFD Modellierung, Grundlagen und Anwendungen bei Strömungsprozessen, Springer-Vieweg, Berlin, Heidelberg (2012)10.1007/978-3-642-24378-3_7Search in Google Scholar

Verein Deutscher Maschinen- und Anlagenbau: Kenndaten für die Verarbeitung thermoplastischer Kunststoffe, Teil 2 Rheologie, Hanser, Munich (1982)Search in Google Scholar

Wacker, G. S.: Fast Release Oral Dosage Forms by Injection Molding as One Step Procedure, PhD Thesis, ETH Zürich, Zürich (1988)Search in Google Scholar

Weissenberg, K.: Die Mechanik deformierbarer Körper, Akademie der Wissenschaften, Berlin (1931)Search in Google Scholar

Williams, M. L., Landel, R. F. and Ferry, J. D., “The Temperature Dependence of Relaxation Mechanisms in Amorphous Polymers and Other Glass-Forming Liquids”, J. Am. Chem. Soc., 77, 37073707 (1955)10.1021/ja01619a008Search in Google Scholar

Wysocki, J., Belowski, D., Kalina, M., Kochanski, L., Okopien, B. and Kalina, Z., “Effects of Micronized Fenofibrate on Insulin Resistance in Patients with Metabolic Syndrome”, International Journal Clinical Pharmacol Therapy, 42, 212217 (2004)10.5414/CPP42212Search in Google Scholar PubMed

Received: 2013-11-14
Accepted: 2014-05-20
Published Online: 2014-11-04
Published in Print: 2014-11-30

© 2014, Carl Hanser Verlag, Munich

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