Extrusion: Pharmaceutical Applications

Transcription

1 Extrusion: Pharmaceutical Applications Edited by DENNIS DOUROUMIS School of Science, University UK WILEY A John Sons, Ltd., Publication

2 List Preface 1. Extrusion: Principles 1 Keith Luker Introduction 1.2 Ideal 2 Basics of the Single-screw Extruder Screw Feed Section Screw Compressor Section Screw Metering Section Mixers of Conventional Single-screw Mixers 13 SSE Elongational Mixers Summary 20 References Twin-screw Extruders for Pharmaceutical Extrusion: Technology, Techniques and Practices 23 Dirk Leister, Tom Geilen and Thobias Geissler 2.1 Introduction Extruder Types and Working Principle Individual Parts of a TSE Drive Unit Screws Screw Elements Distributive Flow Elements Discharge Feed Screw Barrel Downstreaming Individual Processing Sections of the TSE Feeding Section Conveying/Melting Section Mixing Section Venting Section 33

3 2.5.5 Extrusion Section Feeding of Solids TSE Operating Parameters Level Screw Speed Feed Rate Residence Time Distribution Effect of Screw Speed and Feed Rate on Temperature Setting up an HME Process using QbD Principles Understanding Knowledge Space Defining Design Space Determining Control Space Summary 42 References Extrusion Developments in the Pharmaceutical Industry 43 Ana Almeida, Bart Claeys, Jean Paul and Chris Vervaet 3.1 Introduction Advantages of HME as Drug Delivery Technology used for HME Applications Active Pharmaceutical Ingredient Solid Dispersions Bioavailability Improvement Controlled Delivery Systems Plasticizers Characterization of Extrudates Thermal Analysis Force Microscopy Residence Time Spectroscopic Techniques X-ray Diffraction (XRD) Microscopy Drug Release Hot-melt Extruded Dosage Forms Oral Drug Delivery Films Vaginal Rings and Implants 3.6 A View to the Future 63 References Solubility Parameters for Prediction of Miscibility in Hot-melt Extruded Formulations 71 Andreas Gryczke Introduction 4.2 Solid Dispersions 72

4 ix 4.3 Basic Assumptions for the Miscibility Prediction Solubility and the Theory Miscibility Estimation of Drug and Monomers Summary 89 References The of Plasticizers in Hot-melt Extrusion 93 Geert Verreck 5.1 Introduction Traditional Plasticizers Plasticizers Specialty Plasticizers Conclusions 107 References Applications of Poly(meth)acrylate Polymers in Melt Extrusion 113 Kathrin Nollenberger and Jessica Albers 6.1 Introduction 6.2 Polymer Characteristics Chemical Structure and Molecular Weight Transition Temperature Plasticizers Viscosity Specific Heat Capacity Hygroscopicity Melt Extrusion of to Design Pharmaceutical Oral Dosage Forms 6.4 Solubility Enhancement Bioavailability Enhancement of BCS Class IV Drugs Controlled Release Dosage Forms ph-dependent Release Taste Masking Summary 140 References Hot-melt Extrusion of and Polyethylene Oxide Mark Hall and Michael Read 7.1 Introduction ' Background

5 x Contents 7.3 Thermal Properties Processing Aids/Additives 7.5 Unconventional Processing Aids: Drugs, Blends Case Studies Ethylcellulose Combinations of Excipients Solubilization Film Forms Abuse Resistance Controlled Release Solubility Parameters Milling of EC, HPMC and PEO Extrudate References 8. Bioadhesion Properties of Films Produced by Hot-melt Extrusion 177 Joshua Boateng and Dennis Douroumis 8.1 Introduction Anatomy of the Oral Cavity and Modes of Drug Transport Structure Modes of Drug Transport and Kinetics Factors Affecting Drug Absorption Mucoadhesive Mechanisms Factors Affecting Mucoadhesion in the Oral Cavity Determination of Mucoadhesion and Mechanical Properties Films Bioadhesive Films Prepared by HME 8.7 Summary 194 References Taste Masking Using Hot-melt Extrusion 201 Dennis Douroumis, Marion and Attila Aranyos 9.1 The Need and Challenges for Masking Bitter APIs 9.2 Organization of the Taste System Taste Perception in and Organization of Peripheral System Transduction Taste Signals Taste Sensing Systems (Electronic for Pharmaceutical Dosage Forms 206 Alpha MOS Electronic Instrumentation and Operational Principles Taste Analysis Taste Masking Efficiency Testing Advantages of E-tongue Taste Analysis

6 xi 9.4 Hot-melt Extrusion: An Effective Means of Taste Masking Taste Masking via Polymer Extrusion Taste Masking via Solid Lipid Extrusion Summary 219 References 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 In Vivo Evaluation of Hot-melt Extruded Solid Dispersions 225 Oral Immediate Release Oral Controlled Release Conclusion 234 References Injection Molding and Hot-melt Extrusion Processing for Pharmaceutical Materials 239 H0yrup Hemmingsen and Martin Rex Olsen Introduction 239 Hot-melt Extrusion in Brief Injection Molding Critical Parameters 242 Melt Temperature Barrel Temperature Cooling Temperature 243 Holding Pressure Holding Time 243 Back Pressure 244 Injection Speed 244 Cooling Time 244 Comparison of Extruded and Material 245 Development of Products for Injection Molding 246 Excipients Stability 248 Process Development 248 Properties of Injection-molded Materials Egalet Technology 251 Controlling Physical State by Means of Hot-melt Extrusion and Injection Molding Anti-tamper Properties of Injection-molded Tablets 254 Concluding 257 References 257

7 xii Contents 12. Laminar Dispersive and Distributive Mixing with Dissolution and Applications to Hot-melt Extrusion 261 Costas G. Gogos, Huiju Liu and Peng Wang Introduction 12.2 Steps in HME Particulate Solids Handling (PSH) Melting Devolatilization Pumping and Pressurization Dispersive and Distributive Mixing HME Processes: Cases I and II II 268 Dissolution of Drug Particulates in Melt Process Variables Variables Material Variables Case Study: Acetaminophen and oxide) Determination of Solubility of APAP in PEO 280 References Technological Considerations Related to of Hot-melt Extrusion Processes 285 Adam Dreiblatt 13.1 Introduction Scale-up Terminology Scale-up: Batch Size Scale-up: Feed Rate Scale-up: Extruder Diameter Scale-up Volumetrie Scale-up: Volumetrie Scale-up: Diameter Ratio Volumetrie Scale-up: Screw Design Power Scale-up Heat Transfer Scale-up Die Scale-up Conclusion 299 References Devices and Implant Systems by Hot-melt Extrusion 301 Andrew Loxley 14.1 Introduction 301 HME in Device Development Hot-melt Extruder Types 303

8 xiii 14.4 Comparison of HME Devices and Oral Dosage Forms HME Processes for Device Fabrication Issues with HME in preparing Devices Devices and Implants Locations Simple Devices Non-medicated Prolonged Tissue Contact Devices Medicated (Drug-eluting) Prolonged Tissue Contact Devices 14.7 Release Kinetics Mechanisms of API Release Example In Vitro Drug Elution Profiles Conclusions 321 References 15. Hot-melt Extrusion: An FDA Perspective on Product and Process Understanding 323 Gupta and Mansoor A. Khan 15.1 Introduction Quality by Design 325 Utilizing QbD for HME Process Understanding 328 References 16. Improved Process Understanding and Control of a Hot-melt Extrusion Process with Spectroscopy 333 Chris Heil and Jeffrey Hirsch 16.1 Vibrational Spectroscopy Introduction Near-infrared Method Development Near-infrared Probes and Fiber Optics 344 for Monitoring the Start-up of a HME Process 347 NIR for Improved Process Understanding and Control 350 References 353 Index 355