Practical guide to hot-melt extrusion : continuous manufacturing and scale-up

249 Pages·2015·3.928 MB·English

by  Mohammed Maniruzzaman

Practical Guide to
Hot-Melt Extrusion:
Continuous Manufacturing
and Scale-up
Editor:
Mohammed Maniruzzaman
A Smithers Group Company
Shawbury, Shrewsbury, Shropshire, SY4 4NR, United Kingdom
Telephone: [phone] Fax: [phone]
http://www.polymer-books.com
First Published in 2015 by
Smithers Rapra Technology Ltd
Shawbury, Shrewsbury, Shropshire, SY4 4NR, UK
©Smithers Information Ltd., 2015
All rights reserved. Except as permitted under current legislation no part
of this publication may be photocopied, reproduced or distributed in any
form or by any means or stored in a database or retrieval system, without
the prior permission from the copyright holder.
A catalogue record for this book is available from the British Library.
Every effort has been made to contact copyright holders of any material reproduced
within the text and the authors and publishers apologise if
any have been overlooked.
ISBN: 978-1-91024-265-0 (hardback)
978-1-91024-211-7 (softback)
978-1-91024-212-4 (ebook)
Typeset by Integra Software Services Pvt. Ltd.
Printed and bound by Lightning Source Inc.
P
reface
Practical Guide to Hot-Melt Extrusion: Continuous Manufacturing and Scale-up
covers the main process technology (vertical over horizontal extrusion systems),
operation principles and theoretical background of hot-melt extrusion (HME)
techniques. It then continues by focusing on various novel applications (e.g., solubility
enhancement, taste masking, controlled-release/sustained-release drug delivery). As
per the recent trend of regulatory authority, taste masking has been an emerging topic
and to date is considered a real challenge for the design and optimisation of drug
products. The book then includes some recent and novel HME applications, case
studies such as continuous co-crystallisations, use of novel excipients for continuous
HME application and polymorphic transformation monitoring during the HME
processing with respect to long-term stability and product performance. Scale-up
considerations, case studies and regulatory issues during continuous HME processing
are also included in this book.
Major topics covered include: the principles and process technology of HME in
single-screw and twin-screw extrusion techniques; scale-up case studies; taste masking
analysis using HME (in vivo and in vitro); solubility enhancements of poorly soluble
active pharmaceutical ingredients using the HME technique as a means of continuous
co-crystallisation; polymorphic transformation of crystalline drugs; devices used
to process by HME; as well as providing an understanding into the regulatory
perspectives relating to HME based products and their production methods. Various
aspects of continuous manufacturing and the use of novel excipients for scale-up
methodologies are discussed at the end of the book.
Practical Guide to Hot-Melt Extrusion: Continuous Manufacturing and Scale-up
would be an essential multidisciplinary guide to the emerging pharmaceutical uses
and applications for researchers in both academia and across industries working
in the areas of drug formulation and delivery, polymers and materials sciences
(pharmaceutical engineering and processing) for, (but not limited to) the following
reasons:
iii
Practical Guide to Hot-Melt Extrusion: Continuous Manufacturing and Scale-up
• Emerging HME processes and applications for multiple drug delivery.
• Solid-state engineering, solvent free co-crystals manufacturing and solubility
enhancement, controlled-release taste masking and sustained-release case
studies from a continuous manufacturing viewpoint. Scale-up case study and a
consideration of the issues relating to the regulatory guidelines for continuous
manufacturing involving emerging HME techniques.
Dr. Mohammed Maniruzzaman
University of Greenwich, UK, 2015
iv
Dedication
To my dearest parents, parents in-law, sweet sister, little brother
and
To my lovely wife

C
ontents
Preface ..........................................................................................................iii
Contents .......................................................................................................vii
Contributors .................................................................................................xv
1 Introduction to Hot-Melt Extrusion, Continuous Manufacturing:
Scale-up via Hot-Melt Extrusion ...................................................................1
1 Background .............................................................................1
1.1 Introduction ............................................................................1
1.1.1 Hot-Melt Extrusion Process Technology .................2
1.1.2 Equipment ..............................................................3
1.1.3 Benefits and Drawbacks to Hot-Melt Extrusion ......4
1.1.4 Application of Hot-Melt Extrusion .........................5
1.1.5 Materials used in Hot-Melt Extrusion Processes .....6
1.1.6 Development of Sustained-release Formulations ......7
1.1.7 Marketed Products ..................................................7
1.2 Continuous Manufacturing .....................................................8
1.3 Scale-up via Hot-Melt Process ...............................................10
1.3.1 Case Study: Scale-up of a Hot-Melt Extrusion
Process using Soluplus® as Carrier .........................11
1.4 Conclusions ..........................................................................14
References .........................................................................................15
2 Hot-Melt Extrusion as Continuous Manufacturing Technique,
Current Trends and Future Perspectives .....................................................19
2.1 Hot-Melt Extrusion as Continuous Manufacturing
Technique ..............................................................................19
2.1.1 Hot-Melt Extrusion Equipment ...................................21
2.1.2 Single-screw Extruder ..................................................24
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Practical Guide to Hot-Melt Extrusion: Continuous Manufacturing and Scale-up
2.1.3 Twin-screw Extruders ............................................24
2.1.4 Role of Glass Transition Temperature ...................26
2.1.5 Role of Mechanical Parameters .............................26
2.1.6 Use of Plasticisers or Surfactants ..........................26
2.1.7 Challenges and Opportunities ...............................26
2.2 Background Information on Batch Processing .......................27
2.2.1 Past and Future Trends of Continuous
Manufacturing ......................................................28
2.2.2 Conventional Batch Process Design .......................29
2.2.3 Production Parameters .........................................29
2.2.4 Production Parameters in Batch Processing ...........29
2.2.4.1 Active Pharmaceutical Ingredient(s)
Manufacturing Site .............................29
2.2.4.2 Formulation Development...................29
2.2.4.3 Industrial Scale-up ..............................30
2.2.4.4 Regulatory Guidelines .........................30
2.2.5 Validation of Batch Processing ..............................30
2.2.6 In-line Continuous Monitoring Techniques ...........30
2.3 Assimilation of Complete Quality-by-Design Models ............35
2.3.1 Chief Modification in Procedural Expertise
for Continuous Manufacturing .............................35
2.3.2 Process Parameters for Preformulation for
Hot-Melt Extrusion ...............................................36
2.3.3 Implementation of a New Product
Development Process .............................................36
2.3.3.1 Modelling Simulation of
Hot-Melt Extrusion Process ................36
2.3.4 Flow Chart Model for Continuous
Hot-Melt Extrusion based Pharmaceutical
Manufacturing Process .........................................39
2.3.5 Foremost Alteration in Structural Provisions for
Quality and Technical Operations .........................41
2.3.6 Potential Benefits of Continuous
Hot-Melt Extrusion Manufacturing ......................44
2.3.7 Regulatory Issues Related to
Hot-Melt Extrusion ...............................................44
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Contents
2.3.8 Process Analytical Technology Framework ............45
2.4 Conclusion ............................................................................46
References .........................................................................................47
3 Co-extrusion as a Novel Approach in Continuous
Manufacturing Compliance .........................................................................53
3 Background .......................................................................................53
3.1 Introduction ..........................................................................53
3.2 Applications of Co-extrusion via Hot-Melt
Extrusion in Continuous Manufacturing ...............................54
3.2.1 Problem Encountered During Co-extrusion ..........55
3.2.2 Variation of the Die Temperature ..........................55
3.2.3 Swelling of the Die ................................................55
3.2.4 Viscosity Matching ...............................................56
3.2.5 Adhesion ..............................................................56
3.2.6 Interdiffusion .......................................................56
3.2.7 Delamination .......................................................57
3.3 Pharmaceutical Applications ................................................57
3.3.1 Pharmaceutical Significance of the
Co-extrusion Technique ........................................57
3.4 Case Study ............................................................................58
3.5 Conclusions ..........................................................................59
References .........................................................................................59
4 Solid-state Engineering of Drugs using Melt Extrusion in
Continuous Process .....................................................................................63
4 Introduction ......................................................................................63
4.1 Dissolution Enhancement ......................................................63
4.1.1 Use of Novel Inorganic Excipients .........................63
4.1.2 Use of Polymers to Enhance Dissolutions of
Poorly Water-soluble Active Pharmaceutical
Ingredients ............................................................67
4.1.3 Continuous Co-crystallisation Engineering ............68
4.1.4 Polymorphic Transformations via
Hot-Melt Extrusion ..............................................69
ix