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Hot-Melt Extrusion: The Process-Product-Performance Interplay

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Book cover Discovering and Developing Molecules with Optimal Drug-Like Properties

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 15))

Abstract

Hot-melt extrusion is commonly used to manufacture amorphous solid dispersions. This chapter focuses on the process-formulation-performance interplay of a hot-melt-extruded product within the framework of a hypothetical phase diagram. Special attention is paid to the liquidous curve and melt mixing, the mixed-phase glass transition temperature, and hypothetical lower and upper critical solution temperatures. With a complete understanding of the liquidous curve, rheological properties, and the thermal liabilities, a workable processing temperature range for hot-melt extrusion can be defined. Strategies and processing solutions are given to minimize or avoid thermal degradation. Finally, the heat, mass, and momentum balances are outlined and can be leveraged to model the extrusion process when appropriate material properties are understood. The fundamental concepts provided herein will facilitate successful manufacture and scale-up of the extrusion process.

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Authors and Affiliations

  1. Celgene Corporation, 86 Morris Ave, Summit, NJ, 07901, USA

    Nathan Boersen

  2. Formulation Sciences, Merck & Co., 770 Sumneytown Pike, West Point, PA, 19486-0004, USA

    Chad Brown & Patrick Marsac

  3. Merck & Co., Summit, NJ, USA

    James DiNunzio

  4. Pharmaceutical Commercialization Technology, Merck & Co., 770 Sumneytown Pike, West Point, PA, 19486, USA

    David Johnson & Robert Meyer

  5. Merck & Co., Inc., Formulation Sciences, West Point, PA, USA

    Craig McKelvey

Authors
  1. Nathan Boersen
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  2. Chad Brown
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  3. James DiNunzio
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  4. David Johnson
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  5. Patrick Marsac
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  6. Robert Meyer
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  7. Craig McKelvey
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Corresponding author

Correspondence to Patrick Marsac .

Editor information

Editors and Affiliations

  1. Pharmaceutical Sciences & Clinical Supply, Merck & Co, Inc., West Point, Pennsylvania, USA

    Allen C Templeton

  2. Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, USA

    Stephen R. Byrn

  3. Discovery Pharmaceutics, Bristol-Myers Squibb, Wallingford, Connecticut, USA

    Roy J Haskell

  4. Department of Medicinal Chemistry, University of Kansas School of Pharmacy, Lawrence, Kansas, USA

    Thomas E. Prisinzano

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Boersen, N. et al. (2015). Hot-Melt Extrusion: The Process-Product-Performance Interplay. In: Templeton, A., Byrn, S., Haskell, R., Prisinzano, T. (eds) Discovering and Developing Molecules with Optimal Drug-Like Properties. AAPS Advances in the Pharmaceutical Sciences Series, vol 15. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1399-2_11

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