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| List of Contributors | |
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| Preface | |
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| Single-screw Extrusion: Principles | |
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| Introduction | |
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| Ideal Compounding | |
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| Basics of the Single-screw Extruder | |
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| Screw Feed Section | |
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| Screw Compressor Section | |
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| Screw Metering Section | |
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| Mixers | |
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| Limitations of Conventional Single-screw Mixers | |
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| SSE Elongational Mixers | |
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| Summary | |
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| References | |
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| Twin-screw Extruders for Pharmaceutical Hot-melt Extrusion: Technology, Techniques and Practices | |
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| Introduction | |
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| Extruder Types and Working Principle | |
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| Individual Parts of a TSE | |
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| Drive Unit | |
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| Screws | |
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| Screw Elements | |
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| Distributive Flow Elements | |
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| Discharge Feed Screw | |
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| Barrel | |
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| Downstreaming | |
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| Individual Processing Sections of the TSE | |
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| Feeding Section | |
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| Conveying/Melting Section | |
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| Mixing Section | |
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| Venting Section | |
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| Extrusion Section | |
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| Feeding of Solids | |
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| TSE Operating Parameters | |
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| Filling Level | |
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| Screw Speed | |
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| Feed Rate | |
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| Residence Time Distribution | |
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| Effect of Screw Speed and Feed Rate on Melt Temperature | |
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| Setting up an HME Process using QbD Principles | |
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| Understanding Knowledge Space | |
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| Denning Design Space | |
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| Determining Control Space | |
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| Summary | |
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| References | |
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| Hot-melt Extrusion Developments in the Pharmaceutical Industry | |
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| Introduction | |
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| Advantages of HME as Drug Delivery Technology | |
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| Formulations used for HME Applications | |
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| Active Pharmaceutical Ingredient | |
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| Solid Dispersions | |
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| Bioavailability Improvement | |
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| Controlled Delivery Systems | |
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| Plasticizers | |
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| Characterization of Extrudates | |
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| Thermal Analysis | |
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| Atomic Force Microscopy | |
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| Residence Time | |
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| Spectroscopic Techniques | |
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| X-ray Diffraction (XRD) | |
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| Microscopy | |
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| Drug Release | |
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| Hot-melt Extruded Dosage Forms | |
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| Oral Drag Delivery | |
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| Films | |
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| Vaginal Rings and Implants | |
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| A View to the Future | |
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| References | |
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| Solubility Parameters for Prediction of Drug/Polymer Miscibility in Hot-melt Extruded Formulations | |
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| Introduction | |
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| Solid Dispersions | |
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| Basic Assumptions for the Drug-polymer Miscibility Prediction | |
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| Solubility and the Flory-Huggins Theory | |
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| Miscibility Estimation of Drug and Monomers | |
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| Summary | |
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| References | |
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| The Influence of Plasticizers in Hot-melt Extrusion | |
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| Introduction | |
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| Traditional Plasticizers | |
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| Non-traditional Plasticizers | |
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| Specialty Plasticizers | |
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| Conclusions | |
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| References | |
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| Applications of Poly(meth)acrylate Polymers in Melt Extrusion | |
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| Introduction | |
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| Polymer Characteristics | |
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| Chemical Structure and Molecular Weight | |
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| Glass Transition Temperature | |
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| Plasticizers | |
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| Thermostability | |
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| Viscosity | |
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| Specific Heat Capacity | |
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| Hygroscopicity | |
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| Melt Extrusion of Poly(methacrylates) to Design Pharmaceutical Oral Dosage Forms | |
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| Solubility Enhancement | |
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| Bioavailability Enhancement of BCS Class IV Drugs | |
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| Controlled Release | |
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| Time-controlled-release Dosage Forms | |
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| pH-dependent Release | |
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| Taste Masking | |
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| Summary | |
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| References | |
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| Hot-melt Extrusion of Ethylcellulose, Hypromellose and Polyethylene Oxide | |
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| Introduction | |
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| Background | |
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| Thermal Properties | |
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| Processing Aids/Additives | |
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| Unconventional Processing Aids: Drags, Blends | |
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| Case Studies | |
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| Ethylcellulose | |
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| Combinations of Excipients | |
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| Solubilization | |
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| Film | |
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| Unique Dosage Forms | |
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| Abuse Resistance | |
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| Controlled Release | |
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| Solubility Parameters | |
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| Milling of EC, HPMC and PEO Extrudate | |
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| References | |
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| Bioadhesion Properties of Polymeric Films Produced by Hot-melt Extrusion | |
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| Introduction | |
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| Anatomy of the Oral Cavity and Modes of Drug Transport | |
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| Structure | |
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| Modes of Drug Transport and Kinetics | |
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| Factors Affecting Drug Absorption | |
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| Mucoadhesive Mechanisms | |
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| Factors Affecting Mucoadhesion in the Oral Cavity | |
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| Determination of Mucoadhesion and Mechanical Properties of Films | |
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| Bioadhesive Films Prepared by HME | |
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| Summary | |
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| References | |
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| Taste Masking Using Hot-melt Extrusion | |
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| The Need and Challenges for Masking Bitter APIs | |
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| Organization of the Taste System | |
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| Taste Perception in Humans and Organization of Peripheral System | |
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| Transduction of Taste Signals | |
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| Taste Sensing Systems (Electronic Tongues) for Pharmaceutical Dosage Forms | |
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| Alpha MOS Electronic Tongue: Instrumentation and Operational Principles | |
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| Taste Analysis | |
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| Taste Masking Efficiency Testing | |
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| Advantages of E-tongue Taste Analysis | |
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| Hot-melt Extrusion: An Effective Means of Taste Masking | |
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| Taste Masking via Polymer Extrusion | |
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| Taste Masking via Solid Lipid Extrusion | |
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| Summary | |
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| References | |
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| Clinical and Preclinical Studies, Bioavailability and Pharmacokinetics of Hot-melt Extruded Products | |
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| Introduction to Oral Absorption | |
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| In Vivo Evaluation of Hot-melt Extruded Solid Dispersions | |
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| Oral Immediate Release | |
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| Oral Controlled Release | |
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| Implants | |
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| Conclusion | |
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| References | |
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| Injection Molding and Hot-melt Extrusion Processing for Pharmaceutical Materials | |
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| Introduction | |
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| Hot-melt Extrusion in Brief | |
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| Injection Molding | |
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| Critical Parameters | |
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| Melt Temperature | |
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| Barrel Temperature | |
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| Cooling Temperature | |
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| Holding Pressure | |
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| Holding Time | |
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| Back Pressure | |
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| Injection Speed | |
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| Cooling Time/Cycle Time | |
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| Example: Comparison of Extruded and Injection-molded Material | |
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| Development of Products for Injection Molding | |
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| Excipients | |
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| Stability | |
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| Process Development | |
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| Properties of Injection-molded Materials | |
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| Egalet� Technology | |
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| Controlling Physical State by Means of Hot-melt Extrusion and Injection Molding | |
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| Anti-tamper Properties of Injection-molded Tablets | |
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| Concluding Remarks | |
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| References | |
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| Laminar Dispersive and Distributive Mixing with Dissolution and Applications to Hot-melt Extrusion | |
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| Introduction | |
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| Elementary Steps in HME | |
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| Paniculate Solids Handling (PSH) | |
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| Melting | |
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| Devolatilization | |
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| Pumping and Pressurization | |
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| Dispersive and Distributive Mixing | |
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| HME Processes: Cases I and II | |
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| Case I | |
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| Case II | |
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| Dissolution of Drug Particulates in Polymeric Melt | |
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| Process Variables | |
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| Equipment Variables | |
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| Material Variables | |
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| Case Study: Acetaminophen and Poly(ethylene oxide) | |
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| Determination of Solubility of APAP in PEO | |
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| References | |
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| Technological Considerations Related to Scale-up of Hot-melt Extrusion Processes | |
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| Introduction | |
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| Scale-up Terminology | |
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| Scale-up: Batch Size | |
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| Scale-up: Feed Rate | |
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| Scale-up: Extruder Diameter | |
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| Volumetric Scale-up | |
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| Volumetric Scale-up: Length/Diameter (L/D) | |
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| Volumetric Scale-up: Diameter Ratio | |
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| Volumetric Scale-up: Screw Design | |
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| Power Scale-up | |
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| Heat Transfer Scale-up | |
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| Die Scale-up | |
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| Conclusion | |
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| References | |
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| Devices and Implant Systems by Hot-melt Extrusion | |
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| Introduction | |
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| HME in Device Development | |
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| Hot-melt Extruder Types | |
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| Comparison of HME Devices and Oral Dosage Forms | |
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| HME Processes for Device Fabrication | |
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| Issues with HME in preparing Drug-eluting Devices | |
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| Devices and Implants | |
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| Anatomical Device Locations | |
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| Simple Devices | |
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| Non-medicated Prolonged Tissue Contact Devices | |
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| Medicated (Drug-eluting) Prolonged Tissue Contact Devices | |
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| Release Kinetics | |
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| Mechanisms of API Release | |
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| Example In Vitro Drug Elution Profiles | |
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| Conclusions | |
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| References | |
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| Hot-melt Extrusion: An FDA Perspective on Product and Process Understanding | |
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| Introduction | |
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| Quality by Design | |
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| Utilizing QbD for HME Process Understanding | |
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| References | |
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| Improved Process Understanding and Control of a Hot-melt Extrusion Process with Near-Infrared Spectroscopy | |
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| Vibrational Spectroscopy Introduction | |
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| Near-infrared Method Development | |
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| Near-infrared Probes and Fiber Optics | |
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| NTR for Monitoring the Start-up of a HME Process | |
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| NIR for Improved Process Understanding and Control | |
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| References | |
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| Index | |