Drug Delivery Trends: Volume 3: Expectations and Realities of Multifunctional Drug Delivery Systems

Drug Delivery Trends
Copyright
Contributors
Preface
1 -  Bioactive hybrid nanowires: a new in trend for site-specific drug delivery and targeting
	1. Introduction
	2. Types of nanowires
	3. Production methods
		3.1 Top-down method
		3.2 Bottom-up method
	4. Applications of nanowires
		4.1 Nanowires in bioanalytical chemistry
		4.2 Nanowires as biosensors in medical diagnosis
		4.3 Nanowires for delivery of chemotherapeutics
	5. Conclusions
	Acknowledgments
	References
2 - Opportunities and challenges of 3D-printed pharmaceutical dosage forms
	1. Introduction
	2. Materials
		2.1 Aliphatic polyesters
		2.2 Cellulose ethers and esters
		2.3 Acrylic polymers
		2.4 Vinyl polymers
			2.4.1 Novel polymers in the market
			2.4.2 Additives
	3. Technology details
		3.1 Vat photopolymerization
			3.1.1 Stereolithography apparatus
			3.1.2 Digital light processing
			3.1.3 Continuous liquid interface production
		3.2 Powder bed fusion processes
			3.2.1 Selective laser sintering process/laser sintering process
			3.2.2 Powder binding technology
		3.3 3D material extrusion—fused filament fabrication
			3.3.1 Postprocessing
	4. Regulatory and quality considerations
	5. Pharmaceutical applications for drug delivery
		5.1 Tunable release technologies
		5.2 Paste/gel extrusion-based technologies
	6. Conclusions
	References
	Further reading
3 - Marketing authorization and licensing of medicinal products in EU: Regulatory aspects
	1. Introduction
	2. European Union legal framework, hierarchy, and committees
		2.1 The European Union
		2.2 The European commission [1]
		2.3 Departments and agencies [2]
		2.4 Consumers, health, agriculture and food executive agency [3]
		2.5 Health and food safety department [4]
		2.6 European medicines agency [5]
			2.6.1 Committee for medicinal products for human use [6]
				2.6.1.1 Role
			2.6.2 Pharmacovigilance risk assessment committee [7]
				2.6.2.1 Role
			2.6.3 Committee for medicinal products for veterinary use [8]
				2.6.3.1 Role
					2.6.3.1.1 Assessments
			2.6.4 Committee for Orphan Medicinal Products [9]
				2.6.4.1 Role
			2.6.5 Committee on herbal medicinal products [10]
				2.6.5.1 Role
			2.6.6 Committee for advanced therapies [11]
				2.6.6.1 Role
			2.6.7 Paediatric committee [12]
				2.6.7.1 Role
		2.7 Coordination groups
			2.7.1 Coordination group for mutual recognition and decentralised procedures—human [13]
			2.7.2 Composition
			2.7.3 Meetings and reports
			2.7.4 Safety referrals
	3. Legal framework for licensing medicines for human use in the EU
		3.1 Introduction
		3.2 Directive 2001/83/EC [15]
			3.2.1 Article 6
			3.2.2 Article 8(3)(i)
			3.2.3 Article 10.1
			3.2.4 Article 10.3
			3.2.5 Article 10a
			3.2.6 Article 10b
			3.2.7 Article 10c
		3.3 Regulation (EC) No. 726/2004 [16]
		3.4 EudraLex [17]
		3.5 Volume 2A—Chapter 1
			3.5.1 Marketing authorization
			3.5.2 National authorization
			3.5.3 Union authorizations
			3.5.4 Notion of “global marketing authorization”
			3.5.5 Validity of the marketing authorization
				3.5.5.1 Renewal
				3.5.5.2 Cessation of the marketing authorization if the medicinal product is not marketed
			3.5.6 Naming of a medicinal product
			3.5.7 Transparency
			3.5.8 Multiple application
				3.5.8.1 Centralized application
				3.5.8.2 Mutual recognition and decentralized procedures
				3.5.8.3 Concept of “applicant and marketing authorization holder”
		3.6 Marketing authorization procedures
			3.6.1 Centralized procedure
			3.6.2 Decentralized procedure and mutual recognition procedure
			3.6.3 Decentralized procedure
			3.6.4 Mutual recognition procedure
			3.6.5 Independent national procedures
		3.7 Paediatric requirements for medicinal products
		3.8 Union referrals
			3.8.1 Referral according to Article 29 of Directive 2001/83/EC
			3.8.2 Referral in accordance with Article 30(1) of Directive 2001/83/EC
			3.8.3 Referral in accordance with Article 30(2) of Directive 2001/83/EC
			3.8.4 Referral in accordance with Article 31 of Directive 2001/83/EC
			3.8.5 Referral in accordance with Article 107i of directive 2001/83/EC
		3.9 Application types
			3.9.1 Applications according to Article 8(3) of Directive 2001/83/EC
			3.9.2 Applications according to Article 10 of Directive 2001/83/EC
				3.9.2.1 Reference medicinal product
				3.9.2.2 European reference medicinal product
				3.9.2.3 Particularities for application according to Article 10
				3.9.2.4 Applications in accordance with paragraph 3 of Article 10 (“hybrid medicinal product”)
				3.9.2.5 Applications according to Article 10a of Directive 2001/83/EC
				3.9.2.6 Well-established medicinal use
				3.9.2.7 Documentation
				3.9.2.8 Applications according to Article 10b of Directive 2001/83/EEC
				3.9.2.9 Applications according to Article 10c of Directive 2001/83 /EC
		3.10 Data exclusivity and market protection
			3.10.1 Protection periods and global marketing authorization
				3.10.1.1 Extension of the 10-year period in Article 10(1) in the case of new therapeutic indications
				3.10.1.2 One-year period of protection for new indications of well-established substances
				3.10.1.3 One-year period of protection for data supporting a change of classification
		3.11 Variations and extensions
			3.11.1 Variations
				3.11.1.1 Minor variations of Type IA
				3.11.1.2 Minor variations of Type IB
				3.11.1.3 Major variations of Type II
		3.12 Extensions
	4. Conclusion
	Acknowledgments
	References
4 - Clinical considerations on micro- and nanodrug delivery systems
	1. Introduction
	2. Outline of drug development
	3. Micro- and nanoparticles in drug delivery
		3.1 Nonvesicular drug delivery systems
			3.1.1 Microemulsions
			3.1.2 Nanoemulsions
			3.1.3 SLNs
			3.1.4 NLCs
			3.1.5 Polymeric nanoparticles
			3.1.6 Polymeric microparticles
		3.2 Vesicular drug delivery systems
			3.2.1 Liposomes
			3.2.2 Transfersomes
			3.2.3 Ethosomes
			3.2.4 Niosomes
	4. Applications of micro- and nanoparticles
		4.1 Cancer therapy
		4.2 Nanoparticles as diagnostic agents
		4.3 Treatment of acquired immunodeficiency syndrome
		4.4 Delivery of nutraceuticals
	5. Regulatory aspects of nanotechnology-based products
	6. Conclusion
	References
5 - Nanoparticulate treatments for oral delivery
	1. Introduction
	2. Need for nanotechnology in oral solid dosage forms
		2.1 Bioavailability enhancement
		2.2 Targeting specific regions of the physiology
		2.3 Improved physiological stability
		2.4 Sustained or controlled release effect
	3. Formulation perspectives
		3.1 Solid lipid nanoparticles (SLNs)
			3.1.1 Hot melt extrusion
			3.1.2 Solvent emulsification/evaporation
			3.1.3 Hot/cold homogenization [33,40]
			3.1.4 Microemulsion [41]
			3.1.5 Supercritical fluid
		3.2 Polymeric nanoparticles
		3.3 Nanomicelles
		3.4 Nanosuspensions
	4. Challenges
	5. Conclusions
	Abbreviations
	References
6 - Pharmaceutical mini-tablets: a revived trend
	1. Introduction
	2. Advantages of mini-tablets
		2.1 Dosages
		2.2 Customized delivery
		2.3 Improving patient compliance
		2.4 Combination therapy
		2.5 Dose range finding
		2.6 Disintegration times
		2.7 Product design
		2.8 Caregivers
		2.9 Excipients
		2.10 Marketed mini-tablets
		2.11 Packaging
	3. Manufacturing
	4. Types of mini-tablets
		4.1 Pediatric mini-tablets
		4.2 Gastroretentive mini-tablets
		4.3 Orally disintegrating mini-tablets
		4.4 Ocular mini-tablets
		4.5 Bioadhesive vaginal mini-tablets
		4.6 pH-responsive mini-tablets
		4.7 Biphasic mini-tablets
	5. Methods of manufacturing mini-tablets
		5.1 Direct compression
		5.2 Dry granulation
		5.3 Wet granulation
		5.4 Hot melt extrusion
	6. Challenges in the manufacturing of mini-tablets
	7. Coating of mini-tablets
	8. Fluidized-bed coating of mini-tablets
	9. Pan coating of mini-tablets
	10. Novel coating technology for mini-tablets
	11. Packaging of mini-tablets
	12. Encapsulation of mini-tablets into capsules
	13. Unit-dose packing of mini-tablets into sachets
	14. Conclusion
	References
7 - Liquid crystalline drug delivery systems
	1. Introduction
	2. Preparation of LC systems
	3. Characterization of liquid crystalline phases
	4. Applications of liquid crystalline systems
	5. Conclusion
	Acknowledgments
	References
8 - Amorphous drug stabilization using mesoporous materials
	1. Background
	2. Introduction
	3. Mesoporous materials
	4. Structural characterization of mesoporous materials
	5. Mesoporous materials in drug delivery
	6. Different forms of the loaded drug: monolayer versus pore filling
	7. Drug loading techniques
		7.1 Solvent-based loading
		7.2 Solvent-free loading
	8. Performance of drug-loaded mesoporous materials
		8.1 Physical stability
		8.2 Dissolution and in vivo performance
	9. Conclusion
	References
9. “Quality” of pharmaceutical products for human use—underlying concepts and required practices
	1. Introduction
	2. In vivo testing (clinical studies)
		2.1 Bioavailability assessments
			2.1.1 Permeability, absorption, and bioavailability
			2.1.2 A typical bioavailability assessment protocol
		2.2 Bioequivalence assessments
	3. In vitro assessments or drug dissolution testing
	4. Linking in vitro dissolution results to in vivo characteristics/IVIVC
		4.1 Deconvolution and convolution techniques and applications
	5. Regulatory standards and requirements
	6. Limitations and deficiencies of the current practices and requirements for quality assessment
		6.1 Drug product versus drug assessment
		6.2 In vivo assessments
		6.3 In vitro and in vivo correlation
		6.4 In vitro testing
		6.5 Use of computational modeling for linking in vitro and in vivo characteristics
	7. Future outlook
		7.1 Defining the “quality” of products and drugs
		7.2 Lack of clarity of regulatory practices
		7.3 Choice of drug dissolution apparatuses and experimental conditions
		7.4 Drug dissolution testing using simple and common experimental conditions
		7.5 Practices and requirements of predicting plasma drug levels from in vitro drug dissolution results
	8. Conclusions
	References
10 - Optimizing intraperitoneal drug delivery: pressurized intraperitoneal aerosol chemotherapy (PIPAC)
	1. Introduction
		1.1 Poor vascularization of the peritoneum
		1.2 Increased interstitial intratumoral fluid pressure
	2. Optimizing drug therapy in peritoneal metastasis
	3. Limitations of intraperitoneal chemotherapy
	4. Understanding drug uptake into peritoneal nodes
	5. Pharmacokinetics aspects of intraperitoneal chemotherapy
	6. Pharmacodynamic aspects in intraperitoneal chemotherapy
	7. Pharmacological interventions to increase drug uptake
	8. Role of formulation
	9. Physical interventions to improve drug uptake
	10. Specifications for an ideal intraperitoneal drug delivery system
	11. Peritoneal aerosol medicine
	12. Pressurized intraperitoneal aerosol chemotherapy
	13. Electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy
	14. Chemotherapeutic agents used as PIPAC
		14.1 Oxaliplatin
		14.2 Cisplatin and doxorubicin
		14.3 Nab-paclitaxel
		14.4 Caelyx
		14.5 Irinotecan
	15. Preclinical studies
		15.1 Paclitaxel
		15.2 siDNA
		15.3 siRNA
	16. Combination of PIPAC with systemic chemotherapy
	17. In silico modeling
	18. Conclusion and outlook
	References
11 - Upscaling and GMP production of pharmaceutical drug delivery systems
	1. Scalability
		1.1 Top-down methods
			1.1.1 Milling
			1.1.2 High-pressure homogenization
		1.2 Bottom-up methods
			1.2.1 Nanoprecipitation
			1.2.2 Salting out
			1.2.3 Supercritical fluid technology
	2. Sustainability
		2.1 Downstreaming for parenteral formulations
			2.1.1 Purification
			2.1.2 Sterilization
			2.1.3 Freeze drying
		2.2 Downstreaming to solid dosage forms
			2.2.1 Granulation
			2.2.2 Spray drying
	3. GMP compliance
	4. Conclusion
	References
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	L
	M
	N
	O
	P
	Q
	R
	S
	T
	U
	V
	W
	Z