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

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