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Hot-Melt Extrusion Process Design Using Process Analytical Technology

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Melt Extrusion

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 9))

Abstract

Emerging analytical technologies have facilitated a range of testing approaches to assess critical material attributes of pharmaceutical products. As the industry moves toward a continuous manufacturing paradigm, unit operations capable of supporting this approach to drug production will continue to gain importance. Hot-melt extrusion (HME) is one such operation, conducted in a continuous nature, which can be streamlined with the implementation of process analytical technology (PAT) to function as next generation technology. By incorporation of in-line probes and spectral detectors it is possible to determine compositional and process aspects of the production. This chapter describes the underlying principles of extrusion and associated monitoring technologies for implementation of a PAT-based development approach.

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Abbreviations

HME:

Hot-melt extrusion

PAT:

Process analytical technology

QbD:

Quality by design

GI tract:

Gastrointestinal tract

FDA:

(US) Food and drug administration

NIR:

Near-infrared

MFI:

Melt flow index

FT-NIR:

Fourier transformation near-infrared spectrometry

QA:

Quality assurance

DoE:

Design of experiments

CQA:

Critical quality attribute

SPC:

Statistical process control

SE:

Specific energy

SME:

Specific mechanical energy

SMEC:

Specific mechanical energy consumption

API:

Active pharmaceutical ingredient

n :

Extruder screw speed

τ :

Extruder torque

ṁ :

Extruder throughput

P :

Extruder motor power

O :

Extruder engine loading in percent

n max :

Extruder maximum adjustable screw speed

∆P:

Pressure at extruder die

SFL:

Specific (screw) feed load

VSFL:

Volume-specific (screw) feed load

ρ:

Melt density

RT:

Residence time

RTD:

Residence time distribution

\(\bar{t}\) :

Mean residence time

SLR camera:

Single-lens reflex camera

Px:

Pixel

ANOVA:

Analysis of variance

S/N:

Signal to noise ratio

RTmean = \(\bar{t}\) :

Mean residence time

Rev:

Revolution

Vfree :

Free volume of extruder (inner barrel volume minus screw volume)

Tg :

Glass transition temperature

Mw:

Molecular weight

Cp :

Specific heat capacity

DO/DI :

Outer screw diameter to inner screw diameter ratio

DSC:

Differential scanning calorimetry

QC:

Quality control

OOS:

Out of specification

R & D:

Research and development

DF:

Degree of freedom

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Author information

Authors and Affiliations

  1. BASF SE, Lampertheim, Germany

    Andreas Gryczke

Authors
  1. Andreas Gryczke
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Correspondence to Andreas Gryczke .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutics, University of Mississippi School of Phar National Center for Natural Products Res, University, Mississippi, USA

    Michael A. Repka

  2. Pharma Ingredients & Services, BASF Corporation, Tarrytown, New York, USA

    Nigel Langley

  3. Bridgewater, New Jersey, USA

    James DiNunzio

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© 2013 American Association of Pharmaceutical Scientists

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Gryczke, A. (2013). Hot-Melt Extrusion Process Design Using Process Analytical Technology. In: Repka, M., Langley, N., DiNunzio, J. (eds) Melt Extrusion. AAPS Advances in the Pharmaceutical Sciences Series, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8432-5_16

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