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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 | |