Nano- and Microfabrication Techniques in Drug Delivery: Recent Developments and Future Prospects

Description

New materials and manufacturing techniques are evolving with the potential to address the challenges associated with the manufacture of medicinal products that will teach new tricks to old drugs. Nano- and microfabrication techniques include manufacturing methods such as additive manufacturing, lithography, micro-moulding, spray drying, and supercritical fluids among many others. The increasing resolution of new techniques allow researchers to produce objects with micrometric resolutions. This book follows a consecutive order, beginning with a background in the current field and limitations in the manufacturing of different pharmaceutical products, moving on the classification of each method by providing recent examples, and future prospective on a variety of traditional and new Nano and microfabrication techniques. A focus on the materials used to prepare these systems and their biocompatibility, including applied topics such as clinical applications and regulatory aspects also covered, offering the reader a holistic view of this rapidly growing field. Preface About the Book Contents About the Editor Chapter 1: Conducting Polymers as Drug Release Systems 1.1 Introduction 1.1.1 Intrinsically Conducting Polymers 1.1.1.1 Polyacetylene 1.1.1.2 Polyheterocycles as ICPs 1.1.2 Mechanisms of Conductivity 1.1.3 Synthesis of ICPs 1.1.3.1 Chemical Polymerisation 1.1.3.2 Electrochemical Polymerisation 1.2 Methodology 1.3 Drug Delivery Applications of ICPs 1.3.1 ICP Films 1.3.2 ICP Composites 1.3.3 ICP Nanocomposites 1.3.4 ICP Nanoparticles 1.3.5 ICP Hydrogels 1.4 Other Biomedical Applications 1.5 Conclusions References Chapter 2: Electrospinning for Drug Delivery Applications 2.1 Introduction 2.2 Electrospinning and Drug Incorporation Techniques 2.2.1 Blending Electrospinning 2.2.2 Coaxial Electrospinning 2.2.3 Emulsion Electrospinning 2.2.4 Surface Modification Electrospinning 2.3 Advantages and Disadvantages of Drug Loaded Electrospun Nanofibers 2.4 Administration Routes of Drug-Loaded Electrospun Nanofibers 2.4.1 Oral Administration 2.4.2 Vaginal Administration 2.4.3 Transdermal Administration 2.4.4 Ocular Administration 2.4.5 Rectal Administration 2.4.6 Nasal Administration 2.5 Future Perspectives 2.6 Conclusions References Chapter 3: Melt Electrospinning and Electrowriting for Pharmaceutical and Biomedical Applications 3.1 Introduction 3.2 Melt Electrospinning Parameters and Methodologies 3.3 Additives for Melt Electrospinning 3.4 Melt Electrospun Nanocomposites and Blends 3.5 General Applications of Melt Electrospinning 3.6 Use of Melt Electrospinning and Melt Electrowriting in the Pharmaceutical Field 3.7 Use of Melt Electrospinning and Melt Electrowriting in Tissue Engineering and Regenerative Medicine 3.7.1 Biological, Physiological, and Morphological Considerations for Scaffold Design 3.7.2 Frequently Used Polymers for the Application of MES and MEW in Biomedicine 3.7.3 Advances in MES/MEW Scaffold Design According to Target Tissue 3.7.3.1 MES/ MEW for Bone Regeneration 3.7.3.2 MES/MEW for Tissue Engineering of Neocartilage, Tendons, Ligaments, and Muscle 3.7.3.3 MES/MEW for Cardiac and Vascular Tissue Engineering 3.7.3.4 MES/MEW for Wound Dressing Fiber Mats 3.7.3.5 MES/MEW for Neural Regeneration and Stimulation 3.7.3.6 MES/MEW Applications in Dentistry 3.7.3.7 MES/MEW for In Vitro Physiology Studies and In Vivo Models of Disease 3.7.3.8 Future of MES/MEW in Translational Medicine 3.8 Conclusions References Chapter 4: Pharmaceutical Spray Drying 4.1 Introduction 4.2 Spray Drying Process and Process Parameters 4.2.1 Feedstock Preparation 4.2.2 Atomization 4.2.3 Drying 4.2.4 Separation 4.3 Particle Engineering for Direct Compression 4.4 Particle Engineering for Controlled Release Using Aqueous Polymeric Dispersions 4.4.1 Prolonged Release 4.4.2 Delayed Release 4.4.3 Protection and Delivery of Biological Drugs 4.5 Conclusions References Chapter 5: Vat Photopolymerisation Additive Manufacturing for Pharmaceutical Applications 5.1 Introduction and History of Stereolithography 5.2 Theory of Vat Photopolymerisation 5.2.1 Radical Systems 5.2.2 Cationic Systems 5.2.3 Parameters Influencing Rate of Photopolymerisation 5.3 Vat Photopolymerisation-Based 3D Printing Techniques 5.3.1 Stereolithography (SLA) 5.3.2 Digital Light Processing (DLP) 5.3.3 Continuous Liquid Interface Production (CLIP) 5.3.4 Two-Photon Polymerisation (2PP) 5.3.5 Volumetric Printing 5.4 Vat Photopolymerisation in Healthcare 5.4.1 Oral Dosage Forms 5.4.2 Microneedles 5.4.3 Hearing Aids 5.4.4 Dental Applications 5.4.5 Ocular Applications 5.4.6 Medical Devices, Implants and Scaffolds 5.5 Challenges 5.5.1 Leaching of Unreacted Monomers 5.5.2 Drug-Photopolymer Reaction 5.5.3 Unintended Temperature Increase 5.5.4 Printing Optimisations 5.5.5 Regulatory Challenges 5.6 Conclusion References Chapter 6: Semi-solid Extrusion 3D Printing for the Development of Dosage Forms for Special Patient Groups 6.1 Introduction 6.2 Semi-solid Extrusion 3D Printing in Pharmaceutical Production 6.2.1 Semi-solid Extrusion 3D Printing of Dosage Forms for Special Patient Groups 6.2.1.1 Tablets 6.2.1.2 Chewable Formulations 6.2.1.3 Orodispersible Formulations 6.2.1.4 Suppositories 6.3 Conclusions References Chapter 7: Binder Jetting Powder Bed 3D Printing for the Fabrication of Drug Delivery System 7.1 Introduction 7.2 Process Description 7.3 Components of Printing Process 7.3.1 Printheads 7.3.1.1 Drop-on-Demand Printheads Piezoelectric Printheads Thermal Printheads 7.3.1.2 Continuous Jet Printheads 7.3.2 Drugs 7.3.3 Excipients 7.3.4 Binder System 7.3.4.1 Viscosity and Surface Tension 7.3.5 Powder Bed: Liquid Binder Solution/Solvent Interactions 7.4 Interaction of Process Parameters and Material Attributes 7.4.1 Process Parameters 7.4.1.1 Powder Spread Speed 7.4.1.2 Layer Thickness 7.4.1.3 Printing Speed 7.4.1.4 Droplet/Line Spacing 7.4.1.5 Orientation of Printlets 7.4.1.6 Binder Saturation 7.4.1.7 Drying Temperature, Power, and Time 7.4.2 Material Attributes 7.4.2.1 Particle Shape 7.4.2.2 Particle Size Distribution 7.4.2.3 Packing Density 7.4.2.4 Flowability 7.5 Quality Control 7.6 Quality Defects 7.6.1 Coffee Stain Defect 7.6.2 Staircase Effect/Layer Shifting 7.6.3 Delamination 7.6.4 Weight Variation 7.6.5 Shrinkage 7.7 Challenges in Binder Jetting 7.7.1 Solvent Sensitivity 7.7.2 Thermal Stability 7.7.3 Powder Recycling and Wastage 7.7.4 Polymorphic Transformation 7.8 Evolving Regulatory Landscape 7.9 Applications of Binder Jetting 7.9.1 Amorphous Delivery System 7.9.2 Fast Disintegrating and Dispersible Printlets 7.9.3 Sustained Drug Release Delivery System 7.9.4 Microparticles 7.9.5 Printing of Printlets: QR Code 7.9.6 Active Ink-Based Formulations 7.10 Summary References Chapter 8: 3D Printing for Localized Cancer Therapy 8.1 Introduction 8.2 Why 3D Printing? 8.3 3D Printing Techniques 8.4 Different Types of Localized Cancer Therapy 8.4.1 Chemotherapy 8.4.2 Immunotherapy 8.4.3 Gene Therapy 8.4.4 Hyperthermia 8.4.5 Brachytherapy 8.5 3D-Printed Devices for Localized Cancer Therapy 8.5.1 3D-Printed Microneedles for Localized Cancer Therapy 8.5.1.1 Types of Microneedles 8.5.1.2 Materials of Microneedles 8.5.1.3 3D Printing Methods of Microneedles 8.5.1.4 Localized Cancer Therapy Using Microneedles 8.5.2 3D-Printed Scaffolds for Localized Cancer Therapy 8.5.3 3D-Printed Meshes and Patches for Localized Cancer Therapy 8.5.4 3D-Printed Implants for Localized Cancer Therapy 8.5.5 Other 3D-Printed Devices for Localized Cancer Therapy 8.6 Summary References Chapter 9: 4D Printing in Pharmaceutics and Biomedical Applications 9.1 Introduction 9.2 Tissue Engineering 9.2.1 Bone Tissue Regeneration 9.2.2 Neural and Brain Tissue Regeneration 9.2.3 Vascular Regeneration 9.2.4 Cardiac Patches 9.2.5 Muscle Tissue Regeneration 9.2.6 Trachea Regeneration 9.3 Implantable Devices 9.3.1 Stents 9.3.2 Other Medical Devices 9.4 Soft Robots 9.5 Drug Delivery 9.6 Current Limitations and Future Outlook 9.6.1 Design Limitations 9.6.2 Manufacturing Limitations 9.6.3 Material Limitations 9.6.4 Sustainability 9.6.5 FDA Regulation and Commercialization 9.7 Conclusions References Chapter 10: Lithography in Drug Delivery 10.1 Introduction 10.2 Basic Principles, Challenges, and Different Lithography Technologies Applied in Drug Delivery Systems 10.2.1 Photolithography 10.2.1.1 Basic Principles of Photolithography 10.2.1.2 Challenges of Photolithography in Drug Delivery 10.2.2 Soft Lithography 10.2.2.1 Basic Principles of Soft Lithography 10.2.2.2 Challenges of Soft Lithography in Drug Delivery 10.2.3 Nanoimprint Lithography 10.2.3.1 Basic Principles of Nanoimprint Lithography 10.2.3.2 Challenges of Nanoimprint Lithography in Drug Delivery 10.2.4 Flow Lithography 10.2.4.1 Basic Principles of Flow Lithography 10.2.4.2 Challenges of Flow Lithography in Drug Delivery 10.3 Applications of Lithography in Manufacturing Drug Delivery Systems 10.3.1 Fabricating Injectable Drug Particles 10.3.2 Fabricating Skin Microneedle Patch 10.3.3 Fabricating Other Microdevices for Drug Delivery 10.4 Conclusion References Chapter 11: Micro-molding and Its Application to Drug Delivery 11.1 Introduction 11.2 Micro-molding Techniques 11.2.1 Injection Molding 11.2.1.1 Injection Molding Materials 11.2.1.2 Injection Molding Procedures 11.2.1.3 Injection Molding Tools 11.2.1.4 Injection Molding Cycle 11.2.2 Hot Embossing 11.2.3 Casting 11.3 Application of Micro-molding 11.3.1 Immediate-Release Solid Dosage Forms 11.3.2 Implants 11.3.3 Vaginal Rings 11.3.3.1 Vaginal Contraceptive Rings 11.3.3.2 Vaginal Rings for Hormone Replacement Therapy (HRT) for Postmenopausal Men References Chapter 12: Supercritical Fluids: A Promising Technique in Pharmaceutics 12.1 Introduction 12.2 Applications of Supercritical Fluids 12.2.1 scCO2 Processes as Solvent 12.2.2 scCO2 Processes as Antisolvent 12.2.3 scCO2 Processes as a Solute 12.3 Conclusions and Future Perspectives References Chapter 13: Microfluidics as a Tool for the Synthesis of Advanced Drug Delivery Systems 13.1 Introduction 13.2 Main Advantages of Microfluidics for the Synthesis of Drug Delivery Systems 13.3 Microfluidic Flow Patterns and Regimes 13.3.1 Flow Patterns 13.3.2 Flow Regimes 13.4 Microfluidic Devices: Materials and Geometries 13.4.1 Materials for the Fabrication of Microfluidic Devices 13.4.2 Devices for the Synthesis of Drug Delivery Systems 13.4.3 Device Geometries for Droplet Microfluidics 13.5 Microfluidics to Control the Properties of Advanced Drug Delivery Systems 13.5.1 Size 13.5.2 Shape 13.5.3 Surface Properties 13.5.4 Mechanical Properties 13.6 Microfluidics for the Preparation of Advanced Drug Delivery Systems and Their Applications 13.6.1 Lipid-Based Particles 13.6.2 Polymeric and Hybrid Particles 13.6.3 Single and Double Emulsions 13.6.4 Other Types of Drug Delivery Systems 13.7 Scale-Up and Industrial Application 13.8 Conclusions and Future Perspectives References Chapter 14: Nanofluidic Technologies for Drug Screening and Drug Delivery 14.1 Introduction 14.2 Fabrication Technologies 14.2.1 Top-Down Fabrication of Nanofluidic Device 14.2.2 Nano-in-Nano Integration for Fabrication of Functional Nanofluidic Devices 14.2.3 Bonding Technologies for Chip-Based Nanofluidic Devices 14.2.4 Surface Modification of Nanochannels 14.3 Ultrasmall Fluid Manipulation Methods 14.3.1 Nanochannel Valves 14.3.2 Multiphase Fluid Manipulations in Nanochannels 14.4 Separation 14.4.1 Separation Technologies for Biomolecules/Fine Particles in a Living Body 14.4.2 Separation of Biomolecules Based on Microfluidic/Nanofluidic Technologies 14.4.3 Separation of NPs/EVs in Nano- and Microfluidic Devices 14.5 Detection in Nanofluidic Devices 14.5.1 In Situ Detection of Electrokinetic Phenomena in a Single Nanochannel 14.5.2 Optical Detection for Nonfluorescent Molecules 14.5.3 Method for Detection Utilizing Analytical Instruments 14.6 Nanofluidic Devices for High-Throughput Screening 14.7 Applications 14.7.1 Single-Cell Protein Analysis 14.7.2 Ultrafast Protein Digestion and Separation for Shotgun Proteomics 14.8 Summary and Perspectives References Chapter 15: Nanoparticles at the Stage of Clinical Trials 15.1 Conclusions and Future Perspectives References Chapter 16: Nasal Drug Delivery Systems for the Treatment of Diseases of the Central Nervous System and Tuberculosis 16.1 Introduction 16.2 Characteristics of Nasal Drug Delivery 16.2.1 Characteristics and Factors Influencing the Permeability of the Nasal Cavity 16.2.2 Characteristics and Factors Affecting the Permeability of the Intranasal Drugs 16.3 Evaluation of Intranasal Drug Delivery Activity 16.3.1 Experiments to Evaluate the Biological Activity of a Formulation 16.3.2 Some Studies on Drug Release from the Preparations for the Treatment of CNS Disease and Tuberculosis 16.4 Conclusion References Chapter 17: Regulatory Aspects and Barriers in Using Groundbreaking Technologies 17.1 Introduction 17.2 Innovation in Product 17.2.1 Regulatory Pathways for Marketing Authorization of a Medicinal Product 17.2.2 Nanomedicine Products: A First Case Study 17.2.2.1 Additional Data Required for Different Types of Nanomedicines 17.2.2.2 Functionality-Related Modifications of a Nanomedicine Product 17.2.3 Combination Products: A Second Case Study 17.3 Innovation in Process References