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More About This Title Hot-Melt Extrusion - Pharmaceutical Applications
English
Hot-Melt Extrusion: Pharmaceutical Applications covers the main instrumentation, operation principles and theoretical background of HME. It then focuses on HME drug delivery systems, dosage forms and clinical studies (including pharmacokinetics and bioavailability) of HME products. Finally, the book includes some recent and novel HME applications, scale -up considerations and regulatory issues. Topics covered include:
- principles and die design of single screw extrusion
- twin screw extrusion techniques and practices in the laboratory and on production scale
- HME developments for the pharmaceutical industry
- solubility parameters for prediction of drug/polymer miscibility in HME formulations
- the influence of plasticizers in HME
- applications of polymethacrylate polymers in HME
- HME of ethylcellulose, hypromellose, and polyethylene oxide
- bioadhesion properties of polymeric films produced by HME
- taste masking using HME
- clinical studies, bioavailability and pharmacokinetics of HME products
- injection moulding and HME processing for pharmaceutical materials
- laminar dispersive & distributive mixing with dissolution and applications to HME
- technological considerations related to scale-up of HME processes
- devices and implant systems by HME
- an FDA perspective on HME product and process understanding
- improved process understanding and control of an HME process with near-infrared spectroscopy
Hot-Melt Extrusion: Pharmaceutical Applications is an essential multidisciplinary guide to the emerging pharmaceutical uses of this processing technology for researchers in academia and industry working in drug formulation and delivery, pharmaceutical engineering and processing, and polymers and materials science.
This is the first book from our brand new series Advances in Pharmaceutical Technology.Find out more about the series here.
English
After completing his postgraduate studies Dr Douroumis worked as a postdoctoral fellow at the Friedrich – Schiller University of Jena in the Department of Pharmacy, and later as a Senior Scientist at Phoqus Pharmaceutical plc, tasked with the development of sustained/pulsatile release formulations, orally disintegrating tablets and taste masking of bitter drugs; some of these studies were in collaboration with Evonik GmbH in Darmstadt, Germany. He is currently Senior Lecture at the in the University of Greenwich School of Science where he coordinates the course for the MSc Pharmaceutical Science Programme (350 students per annum) and is also a tutor for undergraduate studies in Pharmaceutical Sciences.
English
List of Contributors xv
Preface xvii
1. Single-screw Extrusion: Principles 1
Keith Luker
1.1 Introduction 1
1.2 Ideal Compounding 2
1.3 Basics of the Single-screw Extruder 3
1.4 SSE Elongational Mixers 13
1.5 Summary 20
2. Twin-screw Extruders for Pharmaceutical Hot-melt Extrusion: Technology, Techniques and Practices 23
Dirk Leister, Tom Geilen and Thobias Geissler
2.1 Introduction 23
2.2 Extruder Types and Working Principle 24
2.3 Individual Parts of a TSE 25
2.4 Downstreaming 30
2.5 Individual Processing Sections of the TSE 31
2.6 Feeding of Solids 34
2.7 TSE Operating Parameters 34
2.8 Setting up an HME Process using QbD Principles 40
2.9 Summary 42
3. Hot-melt Extrusion Developments in the Pharmaceutical Industry 43
Ana Almeida, Bart Claeys, Jean Paul Remon and Chris Vervaet
3.1 Introduction 43
3.2 Advantages of HME as Drug Delivery Technology 44
3.3 Formulations used for HME Applications 45
3.4 Characterization of Extrudates 55
3.5 Hot-melt Extruded Dosage Forms 58
3.6 A View to the Future 63
4. Solubility Parameters for Prediction of Drug/Polymer Miscibility in Hot-melt Extruded Formulations 71
Andreas Gryczke
4.1 Introduction 71
4.2 Solid Dispersions 72
4.3 Basic Assumptions for the Drug–polymer Miscibility Prediction 77
4.4 Solubility and the Flory–Huggins Theory 78
4.5 Miscibility Estimation of Drug and Monomers 83
4.6 Summary 89
5. The Influence of Plasticizers in Hot-melt Extrusion 93
Geert Verreck
5.1 Introduction 93
5.2 Traditional Plasticizers 94
5.3 Non-traditional Plasticizers 95
5.4 Specialty Plasticizers 104
5.5 Conclusions 107
6. Applications of Poly(meth)acrylate Polymers in Melt Extrusion 113
Kathrin Nollenberger and Jessica Albers
6.1 Introduction 113
6.2 Polymer Characteristics 116
6.3 Melt Extrusion of Poly(methacrylates) to Design Pharmaceutical Oral Dosage Forms 128
6.4 Solubility Enhancement 128
6.5 Bioavailability Enhancement of BCS Class IV Drugs 132
6.6 Summary 140
7. Hot-melt Extrusion of Ethylcellulose, Hypromellose and Polyethylene Oxide 145
Mark Hall and Michael Read
7.1 Introduction 145
7.2 Background 146
7.3 Thermal Properties 147
7.4 Processing Aids/Additives 147
7.5 Unconventional Processing Aids: Drugs, Blends 149
7.6 Case Studies 151
7.7 Milling of EC, HPMC and PEO Extrudate 168
8. Bioadhesion Properties of Polymeric Films Produced by Hot-melt Extrusion 177
Joshua Boateng and Dennis Douroumis
8.1 Introduction 177
8.2 Anatomy of the Oral Cavity and Modes of Drug Transport 180
8.3 Mucoadhesive Mechanisms 182
8.4 Factors Affecting Mucoadhesion in the Oral Cavity 183
8.5 Determination of Mucoadhesion and Mechanical Properties of Films 183
8.6 Bioadhesive Films Prepared by HME 184
8.7 Summary 194
9. Taste Masking Using Hot-melt Extrusion 201
Dennis Douroumis, Marion Bonnefille and Attila Aranyos
9.1 The Need and Challenges for Masking Bitter APIs 201
9.2 Organization of the Taste System 203
9.3 Taste Sensing Systems (Electronic Tongues) for Pharmaceutical Dosage Forms 206
9.4 Hot-melt Extrusion: An Effective Means of Taste Masking 212
9.5 Summary 219
10. Clinical and Preclinical Studies, Bioavailability and Pharmacokinetics of Hot-melt Extruded Products 223
Sandra Guns and Guy Van den Mooter
10.1 Introduction to Oral Absorption 223
10.2 In Vivo Evaluation of Hot-melt Extruded Solid Dispersions 225
10.3 Conclusion 234
11. Injection Molding and Hot-melt Extrusion Processing for Pharmaceutical Materials 239
Pernille Høyrup Hemmingsen and Martin Rex Olsen
11.1 Introduction 239
11.2 Hot-melt Extrusion in Brief 240
11.3 Injection Molding 241
11.4 Critical Parameters 242
11.5 Example: Comparison of Extruded and Injection-molded Material 245
11.6 Development of Products for Injection Molding 246
11.7 Properties of Injection-molded Materials 251
11.8 Concluding Remarks 257
12. Laminar Dispersive and Distributive Mixing with Dissolution and Applications to Hot-melt Extrusion 261
Costas G. Gogos, Huiju Liu and Peng Wang
12.1 Introduction 261
12.2 Elementary Steps in HME 263
12.3 Dispersive and Distributive Mixing 265
12.4 HME Processes: Cases I and II 265
12.5 Dissolution of Drug Particulates in Polymeric Melt 270
12.6 Case Study: Acetaminophen and Poly(ethylene oxide) 278
12.7 Determination of Solubility of APAP in PEO 280
13. Technological Considerations Related to Scale-up of Hot-melt Extrusion Processes 285
Adam Dreiblatt
13.1 Introduction 285
13.2 Scale-up Terminology 287
13.3 Volumetric Scale-up 290
13.4 Power Scale-up 296
13.5 Heat Transfer Scale-up 298
13.6 Die Scale-up 299
13.7 Conclusion 299
14. Devices and Implant Systems by Hot-melt Extrusion 301
Andrew Loxley
14.1 Introduction 301
14.2 HME in Device Development 302
14.3 Hot-melt Extruder Types 303
14.4 Comparison of HME Devices and Oral Dosage Forms 305
14.5 HME Processes for Device Fabrication 306
14.6 Devices and Implants 310
14.7 Release Kinetics 318
14.8 Conclusions 321
15. Hot-melt Extrusion: An FDA Perspective on Product and Process Understanding 323
Abhay Gupta and Mansoor A. Khan
15.1 Introduction 323
15.2 Quality by Design 325
15.3 Utilizing QbD for HME Process Understanding 328
16. Improved Process Understanding and Control of a Hot-melt Extrusion Process with Near-Infrared Spectroscopy 333
Chris Heil and Jeffrey Hirsch
16.1 Vibrational Spectroscopy Introduction 333
16.2 Near-infrared Method Development 339
16.3 Near-infrared Probes and Fiber Optics 344
16.4 NIR for Monitoring the Start-up of a HME Process 347
16.5 NIR for Improved Process Understanding and Control 350
References 353
Index 355
