165,99 €
Mehr erfahren.
- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
This work is an examination of all aspects of the science in developing effective dosage form for drug delivery Pharmaceutics refers to the subfield of pharmaceutical sciences that develops drug delivery products or devices to optimize the drug's performance once administered. This multidisciplinary field draws on physical chemistry, organic chemistry, and biophysics to generate and refine these crucial elements of medical care. Moreover, incorporating such disparate dimensions of drug product design as material properties and legal regulation bridges the gap between effective chemicals and viable medical treatments. Integrated Pharmaceutics provides a comprehensive introduction to the creation and manufacture of effective dosage forms for drug delivery. It presents its subject following the principles of physical pharmacy, product design, and drug regulations. This tripartite structure allows readers to move from theory to practice, beginning from a firm foundation of physical pharmacy principles, including drug solubility and stability estimation, rheology, and interfacial properties. From there, it proceeds to discussions of drug product design and of harmonizing pharmaceutical design with the regulatory regimens and technological standards of the United States, European Union, and Japan. Readers of the second edition of Integrated Pharmaceutics will also find: * A glossary defining key terms, extensive informative appendices, and a list of references leading to the primary literature in the field for each chapter * Earlier chapters are expanded, with additional new chapters including one entitled "Biotechnology Products" * Supplementary instructor guide with questions and solutions available online for registered professors * Updated regulatory guidelines including quality by design, design space analysis, process analytical technology, polymorphism characterization, blend sample uniformity, and stability protocols Integrated Pharmaceutics is a useful textbook for graduate students in pharmaceutical sciences, drug formulation and design, and biomedical engineering. In addition, professionals in the pharmaceutical industry, including regulatory bodies, will find it a helpful reference guide.
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 2460
Veröffentlichungsjahr: 2022
Ähnliche
Table of Contents
Cover
Title Page
Copyright Page
Dedication Page
Foreword to Second Edition
Foreword to First Edition
Preface to Second Edition
Acknowledgments
Preface to First Edition
Acknowledgments
About the Companion Website
Part I: Applied Preformulation
1 Mathematical Concepts
1.1 Introduction
1.2 Significant Figures and Rounding off Numbers
1.3 The Simple Linear Relationship
1.4 Exponential Rules
1.5 Logarithmic Rules
1.6 Differential Equations
1.7 Expanding and Reducing Formulas
1.8 Weights and Measures
References
Glossary
2 Thermodynamics
2.1 Introduction
2.2 The Zeroth Law of Thermodynamics
2.3 The First Law of Thermodynamics
2.4 The Second Law of Thermodynamics
2.5 The Third Law of Thermodynamics
2.6 Polymorphism
2.7 Physical Stability of Crystal Forms
2.8 Solubility
References
Glossary
3 Solubility and Dissolution
3.1 Introduction
3.2 Methods of API Solubility Enhancement
3.3 Nonionic, Ionic, and Acid–Base Concepts Related to Solubility and Dissolution
3.4 The Solubility of Gas in Liquid
3.5 The Solubility of Liquid in Liquid
3.6 The Solubility of Solid in Liquid
3.7 Disintegration and Dissolution
3.8 Concentration Units
3.9 The Partition Coefficient
3.10 Concluding Remarks
References
Glossary
Appendix
4 Biological Aspects of Formulations
4.1 Introduction
4.2 Bioavailability and Bioequivalence
4.3 Protocols for Determining Bioequivalence
4.4 Bioequivalence Procedure
4.5 FDA‐Approved Methods for Bioequivalence Studies
4.6 Approaches to Improving Bioavailability
References
Glossary
5 Interfacial Properties
5.1 Introduction
5.2 Liquid–Solid Interface
5.3 Liquid–Liquid Interface
5.4 Dosage‐Form Applications
5.5 Case Study: HLB Determination
5.6 Case Study: Determination of Required HLB (rHLB)
References
Glossary
6 Adsorption Phenomenon
6.1 Introduction
6.2 Adsorption on Filters
6.3 Adsorption of Proteins
References
Glossary
7 Rheological Principles
7.1 Introduction
7.2 Newtonian Systems
7.3 Non‐Newtonian Systems
7.4 Viscoelasticity
7.5 Reynolds Number
7.6 Concluding Remarks
References
Glossary
8 Chemical Stability and Shelf‐Life Determination
8.1 Introduction
8.2 Shelf‐Life Determination
8.3 Stability of Biotechnology Products
8.4 Compounded Products and Their Beyond‐Use Dates
References
Glossary
9 Particle Science
9.1 Introduction
9.2 Miromeritics
9.3 Micronization
9.4 Particle Size Preparation and Reduction for Pulmonary Delivery
9.5 Polymeric Particulate Matter
9.6 Nanoparticles
9.7 Segregation of Particles
9.8 Case Studies: Microscopic Particle Size Analysis, Determining Statistically Valid Sample Size, and Comparison of Sieve and Focused Beam Reflectance Measurement Chord Length Particle Size Distributions
References
Glossary
10 Basic Statistics and Design of Experimental Concepts
10.1 Descriptive Statistics
10.2 Inferential Statistics
10.3 Statistical Applications in Quality Control Testing
10.4 Design of Experiment
10.5 Multivariate Analysis (MVA)
10.6 Reliability and Validity Assessment
References
Glossary
11 Formulation Development Concepts
11.1 Preformulation
11.2 Scale‐up Considerations
11.3 Combination Products
11.4 Rate‐Controlled Drug Delivery
11.5 Drug Delivery Technologies for Improving Oral Delivery
11.6 Drug Delivery Technologies for Improving Transmucosal Delivery
11.7 Drug Delivery Technologies for Transdermal Delivery
11.8 Special Considerations for Biotechnology and Protein Delivery Systems
11.9 Drug–Excipient and Excipient–Excipient Interactions
11.10 The Presence of Contaminants in a Formulation
11.11 Other Considerations
References
Glossary
Part II: Product Design
12 The Product Design Process
12.1 Introduction
12.2 Formulation Design
12.3 Process Design
12.4 Container Closure System Design
References
Glossary
12.A Appendix
13 Tablet Product Design
13.1 Introduction
13.2 Formulation Design
13.3 Process Design
13.4 Container Closure System Design
13.5 Risk Management
13.6 Attribute Tests
13.7 New Drug Application Stability Assessment
References
Glossary
13.A Appendix
14 Capsule Product Design
14.1 Introduction
14.2 Hard‐Shell Capsules
14.3 Soft‐Shell Capsules
14.4 Formulation and Process Optimization
14.5 Container Closure System Design
14.6 Risk Management
14.7 Attribute Tests
14.8 New Drug Application Stability Assessment
References
Glossary
14.A Appendix
15 Dispersed System Product Design
15.1 Introduction
15.2 Formulation Design
15.3 Process Design
15.4 Container Closure System Design
15.5 Risk Management
15.6 Attribute Tests
15.7 New Drug Application Stability Assessment
References
Glossary
Appendices
16 Aerosol Product Design
16.1 Introduction
16.2 Inhalation Formulation Design
16.3 Nasal, Buccal, Lingual, and Sublingual Aerosol Formulation Design
16.4 Container Closure System Design
16.5 Risk Management
16.6 Attribute Tests
16.7 New Drug Application Stability Assessment
References
Glossary
16.A Appendix
17 Sterile Injectable Product Design
17.1 Introduction
17.2 Formulation Design
17.3 Process Design
17.4 Container Closure System Design
17.5 Risk Management
17.6 Attribute Tests
17.7 New Drug Application Stability Assessment
References
Glossary
17.A Appendix
18 Ophthalmic Product Design
18.1 Introduction – Eye Anatomy and Physiology
18.2 Formulation Design
18.3 Process Design
18.4 Container Closure System Design
18.5 Attribute Tests
18.6 New Drug Application Stability Assessment
References
Glossary
18.A Appendix
19 Transdermal Product Design
19.1 Introduction – Skin Anatomy and Physiology
19.2 Formulation Design
19.3 Conclusions
References
Glossary
19.A Appendix
20 Oral Modified‐Release Product Design
20.1 Introduction
20.2 FDA and U.S.P. Nomenclature
20.3 Modified‐Release Mechanisms
20.4
In Vitro–In Vivo
Correlations (IVIVC)
20.5 Coatings
20.6 Matrix Systems
20.7 Gastroretentive Devices
20.8 Osmotic‐Controlled Release Systems
20.9 Conclusions
References
Glossary
20.A Appendix
Part III: Regulatory Science
21 Regulatory Practices and Guidelines
21.1 Worldwide Regulatory Agencies
21.2 Good Manufacturing Practice (GMP)
21.3 FDA Inspection and Regulatory Actions (FDA 2020b, 2020d)
References
Glossary
21.A Appendix
22 Regulations for Compounding Pharmacies
22.1 Introduction
22.2 Sections 503A and 503B and Their Differences (FDA 2018a)
22.3 Compounding Guidelines
22.4 Good Compounding Practices (FDA 2007; Skoloff 2009; U.S.P <795> 2020: U.S.P <797> 2020); U.S.P. <1191> 2018; USP29 2006; USP29NF24 2006; OSBP 2017; NDBOPH 2020; NV 2020a; OR 2020; CPE 2017; OK 2020; KY 2016a; WA 2020a; FDA 2020a, 2020b)
22.5 Compounding Sterile Preparations (U.S.P. <797> 2020; WA 2020b; CT 2020; OR 2020; NV 2020b; OK 2020; KY 2016b; NYBOP (n.d.); ASPH 2003, 2020; TU n.d.)
22.6 Stability Criteria and Beyond‐Use Dating of Compounded Non‐Sterile Preparations (U.S.P. <797> 2020; WA 2020b; CT 2020; OR 2020; NV 2020b; OK 2020; KY 2016b; NYBOP (n.d.); ASPH 2003, 2020; TU n.d.)
22.7 Verification (U.S.P. <795> 2020; U.S.P. <797> 2020; WA 2020a, 2020b)
22.8 Patient Counseling (U.S.P. <795> 2020; U.S.P. <797> 2020; WA 2020a, 2020b)
22.9 Patient Monitoring and Adverse Events Reporting (U.S.P. <797> 2020; WA 2020b)
22.10 Pharmacy Compounding Accreditation
22.11 Compounding: Inspections, Recalls, and Other Actions (FDA 2018b; FDA 2018c)
References
Glossary
22.A Appendix
23 IND and NDA Phase‐Appropriate New Drug Development Process
23.1 Introduction
23.2 Preclinical Development Overview (FDA 1998)
23.3 Phase‐Appropriate Clinical Trials Overview (FDA 1998)
23.4 Investigational New Drugs
23.5 Good Laboratory Practice for Nonclinical Laboratories Studies [21CFR58] (FDA 2020c)
23.6 CGMP for Phase 1 Investigational Drugs – Guidance for Industry (FDA 2008)
23.7 Good Clinical Practice [E6(R2)] Guidance for Industry (FDA 2016, 2018b, 2019a)
23.8 NDA Review Process (FDA 1998)
References
Glossary
23.A Appendix
24 Biological, Biosimilar, Generic, and OTC Products
24.1 Biologicals (FDA 2015a, 2015b, 2016b,2018a, 2018b, 2019a, 2019b, 2019c, 2020a; EMA 2019)
24.2 Biosimilars (EMA n.d.-a, n.d.-b; FDA n.d.-a, n.d.-b; Christl n.d.; FDA n.d.-c; Lim n.d., 2013; FDA 2017a, 2017b, 2017c, 2018c, 2020b, 2020c; EMA 2019)
24.3 Generic Drugs (FDA 1998a, 2014b, 2017f, 2017g, 2018e, 2018g, 2019d)
24.4 Over‐the‐Counter Drugs (FDA 1998b, 2016a, 2018g, 2019f, 2020e, 2020f, 2020g)
References
Glossary
24.A Appendix
25 Accelerated New Drug Approval and Expedited Access of New Therapies
25.1 Introduction
25.2 Expedited Review and Approval of New Therapies (HIV n.d.; IOM 1991; FDA 2009a, 2010a, 2011b, 2014)
25.3 Expanded Access to New Therapies (HIV n.d.; FDA 2009a)
25.4 Orphan Drugs (EMA n.d.-a, n.d.-b; WebMD n.d.; FDA 1998a, 2005a, 2018, 2018b, 2020c; IOM 2010)
25.5 Pediatric Drugs (FDA 1998b, 2005b)
25.6 Pediatric Drug Development and the Orphan Drug Act Incentives (FDA 2010c)
25.7 Common EMEA/FDA Application for Orphan Medicinal Product Designation (EMA n.d.-a, n.d.-b; FDA 2009b; FDA 2018)
References
Glossary
26 Post–Drug Approval Activities
26.1 Postmarket Requirements and Commitments (FDA 2016b, 2018f, 2020a, 2020e)
26.2 Postapproval Manufacturing Changes (FDA 2018d, 2020b)
26.3 Clinical Phase 4 Studies: Postmarketing Surveillance and Risk Assessment (FDA 2018d, 2019b)
26.4 Prescription Drug Advertising and Promotional Labeling Direct to Consumers (FDA 1998c)
References
Glossary
26.A Appendix
27 Drug Master Files, EU Dossiers, and API GMP Guidance
27.1 Drug Master Files (FDA 2001, 2011a, 2011b, 2011c, 2011d, 2011e)
27.2 European Marketing Authorization Dossiers
27.3 Good Manufactruing Practice (GMP) Guidance for Active Pharmaceutical Ingredients (Q7) (FDA 2016)
References
Glossary
28 Commissioning and Qualification
28.1 Regulatory Requirements (Health Canada 2009; EU 2015; FDA 2017, 2018a, 2020)
28.2 Preliminary C&Q Activities
28.3 Commissioning
28.4 Qualification and Validation
28.5 Qualification Protocols (ISPE 2001; Health Canada 2009; PIC/S 2018)
28.6 Process Validation (FDA 2014, 2019; PIC/S 2018)
28.7 Cleaning Validation (Health Canada 2008; FDA 2014, 2017; PIC/S 2018)
28.8 Computer Systems Validation (ISPE 2001; EU 2011)
28.9 Change Control (EU 2015; PIC/S 2018)
28.10 Revalidation (CDRH 1995; EU 2015; FDA 2015; PIC/S 2018)
References
Glossary
29 Quality Systems and Controls
29.1 Pharmaceutical Quality System (FDA 2019a)
29.2 Quality Systems Approach to CGMP Regulations
29.3 Inspection of Pharmaceutical Quality Control Laboratories (FDA 2014)
29.4 Pharmacopeias (U.S.P. 2014)
29.5 Analytical Instrument Qualification (U.S.P. <1058> 2019a; FDA 2010)
29.6 Validation of Analytical Procedures (U.S.P. <1225> 2019b; FDA 2000, 2015, 2019b)
29.7 Stability Testing of New Drug Substances and Products (U.S.P. <1150> 2006; ICH 1996; FDA 2018b, 2018c, 2018d)
29.8 Electronic Records; Electronic Signatures (Part 11) (FDA 2019)
References
Glossary
29.A Appendix
30 Safety, Toxicology, and Pharmacogenomics
30.1 Nonclinical Safety Studies (ICH 2009; FDA 2010)
30.2 Safety Pharmacology Studies (ICH 2000)
30.3 Preclinical Safety Evaluation of Biotechnology‐Derived Pharmaceuticals – (FDA 1997; EMA 2011a)
30.4 Carcinogenicity Studies of Pharmaceuticals (ICH 1995)
30.5 Genotoxicity Testing (ICH 1998, 2008)
30.6 Immunotoxicity Studies (ICH 2005b)
30.7 Safety Reporting Requirements
30.8 Pharmacogenomics (NIGMS 2005; ICH 2005b; ORNL 2010)
30.9 Pharmacovigilance (EMA 2011b, 2015, 2021; Eudro n.d.; FDA 2005c, 2005d)
30.10 FDA’s Predictive Toxicology Roadmap (FDA 2017, 2020)
References
Glossary
Appendix
31 Regulatory Science Initiatives for Advancing Public Health
31.1 Introduction
31.2 Advancing Regulatory Science for Public Health – A Framework for FDA’s Regulatory Science Initiatives (FDA 2010)
31.3 Advancing Regulatory Science at FDA – A Strategic Plan (FDA 2018b, 2018c, 2018d, 2018e, 2018f, 2018g, 2018h, 2018i, 2018j, 2018k, 2018l)
31.4 A Collaborative Implementation Framework (FDA 2010, 2011, 2018n)
References
32 Medical Devices
32.1 Introduction (FDA 2018a, 2019a, 2020a)
32.2 Device Determination Steps (FDA 2019a, 2020a)
32.3 Classification and Regulatory Requirements (FDA 2018b, 2020b)
32.4 Current Good Manufacturing Practices (CGMPs) and Quality System Regulation (QSR Regulation) Requirements
32.5 Medical Device Complaint Reporting and Recalls (FDA 2019h, 2019i)
References
Glossary
33 Combination Products
33.1 Introduction (FDA 2018, 2019e, 2020)
33.2 Product Jurisdiction/Assignment of Combination and Non‐Combination Products (FDA 2019a, 2020)
33.3 Premarket and Marketing Applications (21 CFR Parts 312 and 812) (FDA 2019b, 2019c, 2020)
33.4 Current Good Manufacturing Practice – Subpart A (21CFR4) (FDA 2019d)
33.5 Postmarkeing Safety Reporting for Combination Products [21CFR4/Part 4 Regulation of Combination Products/Subpart B] (FDA 2019d)
References
33.A Appendix
34 Dietary Supplements
34.1 Introduction (FDA 2017a, 2019a, 2019b)
34.2 Dietary Ingredients (FDA 2019a, 2019b, 2019c)
34.3 Dietary Supplement Ingredient Advisory List (FDA 2019d)
34.4 DS Labeling: Claims Types and Requirements (FDA 2017b, 2018, 2019e)
34.5 Current Good Manufacturing Practice in Manufacturing, Packaging, Lableing, or Holding Operations for Dietary Supplements (21 CFR Part 111) (FDA 2019f)
34.6 FDA Inspection and Regulatory Actions (see – 21.3 FDA Inspection and Regulatory Actions – see Chapter 21 for details)
References
Glossary (specific terms for DS)
34.A Appendix
35 Animal Drugs and Devices
35.1 FDA Center For Veterinary Medicine (CVM) (FDA 2019a)
35.2 Animal Drug Availability Act of 1996 (FDA 2019b)
35.3 Development and Approval Process (FDA 2017, 2020a)
35.4 CGMP and Others Compliance Requirements
35.5 Animal Drug Manufacturing Inspection – Pre‐Approval (FDA 2006)
35.6 PostMarketing Survellance (FDA 2017, 2019d, 2020a)
References
Index
End User License Agreement
List of Tables
Chapter 3
Table 3.1 Maximum daily exposure of selected solubilizing cosolvents.
Table 3.2 Sucrose octaacetate aqueous solubility at 25 ± 0.2 °C after heatin...
Table 3.A.1 Injectable surfactants, solubilizing, emulsifying, and thickenin...
Chapter 6
Table 6.1 Adsorption isotherms
Chapter 8
Table 8.1 Sucrose octaacetate chemical kinetic observed first‐order regressi...
Table 8.2 Sucrose octaacetate activation energy, extrapolated degradation ra...
Table 8.3 Typical peptide or protein degradation reactions.
Table 8.4 Beyond‐use date for compounded preparations: selected examples.
Chapter 9
Table 9.1 Particle size diameter nomenclature.
Table 9.2 Different microscopic particle diameters.
Table 9.3 Particle size measuring technologies, their measurement principle,...
Table 9.4 Mechanisms for particle segregation (Adapted from Mosby et al. 199...
Table 9.5 Grouped frequency table for particle size determination.
Table 9.6 Grouped frequency table for log normal particle size determination...
Table 9.7 Focused beam reflectance measurement chord length percentage in ea...
Table 9.8 Sieve granule weight percentage in each size interval.
Chapter 11
Table 11.1 QbD: guiding principles.
Table 11.2 Substances found in vaccines.
Chapter 13
Table 13.1 Advantages and disadvantages of tablets.
Table 13.2 Running powder manufacturing process steps.
Table 13.3 Advantages and disadvantages of running powder manufacturing proc...
Table 13.4 Solid‐state physical properties and tablet implications.
Table 13.5 Solution‐and solid‐state chemical properties and tablet implicati...
Table 13.6 Tablet excipient classes and functions
a
.
Table 13.7 Typical accelerated excipient compatibility stability protocol.
Table 13.8 Occupational exposure limits categorization and performance‐based...
Table 13.9 Particle sizes obtained by various mills.
Table 13.10 Theoretical content uniformity based on a binominal distribution...
Table 13.11 Scale‐up factors for V‐blenders.
Table 13.12 Loss tangent and dielectric values for common pharmaceutical exc...
Table 13.13 Film‐coating excipient classes and functions.
Table 13.14 Aqueous film‐coating parameters.
Table 13.15 Permeability through selected packaging materials.
Table 13.16 Risk assessment for a wet granulated embossed film‐coated tablet
Table 13.17 Risk control strategy for a wet granulated embossed film‐coated ...
Table 13.18 NDA stability protocol.
Table 13.19 Reporting, identification, and qualification thresholds for degr...
Chapter 14
Table 14.1 Advantages and disadvantages of hard‐shell capsules compared to t...
Table 14.2 Hard‐shell capsule component classes and functions.
Table 14.3 Typical gelatin hard‐shell capsule formulation.
Table 14.4 Typical hypromellose hard‐shell capsule formulation.
Table 14.5 Typical pullulan hard‐shell capsule formulation.
Table 14.6 Typical hard‐shell starch capsule composition.
Table 14.7 Hard‐shell capsule sizes and capacities.
Table 14.8 Intrinsic dissolution rates of common hard‐shell capsule excipien...
Table 14.9 Lipid formulation classification system.
Table 14.10 Advantages and disadvantages of soft‐shell capsules.
Table 14.11 Soft‐shell capsule component classes and functions.
Table 14.12 Typical soft‐shell gelatin capsule shell composition.
Table 14.13 Typical soft‐shell starch capsule shell composition.
Table 14.14 Typical capsule stability NDA protocol.
Chapter 15
Table 15.1 Dispersed system classification based on the state of matter.
Table 15.2 Advantages and disadvantages of oral liquid coarse dispersed syst...
Table 15.3 Solid‐state physical properties and dispersed system implications...
Table 15.4 Solution‐ and solid‐state chemical properties and dispersed syste...
Table 15.5 Excipient classes and functions for liquid suspensions and solid ...
Table 15.6 Excipient classes and functions for macroemulsions and associatio...
Table 15.7 Topical emulsion formulation.
Table 15.8 Critical micelle concentration values for selected surfactants.
Table 15.9 Advantages and disadvantages of microemulsions.
Table 15.10 NDA stability protocol.
Table 15.A.1 Suspending, viscosity‐enhancing, and structure‐modifying agents...
Table 15.A.2 Sweetening agents.
Table 15.A.3 Flocculating agents and buffers.
Table 15.A.4 Emulsifying agents.
Table 15.A.5 Required HLB for oils and waxes.
Chapter 16
Table 16.1 Advantages and disadvantages of inhalation aerosols.
Table 16.2 Solid‐state physical properties and aerosol implications.
Table 16.3 Solution and chemical properties and their aerosol implications....
Table 16.4 Excipient classes and function.
Table 16.5 Comparative advantages and disadvantages of conventional nebulize...
Table 16.6 Physical properties of HFA‐134a and HFA‐227.
Table 16.7 Advantages and disadvantages of aerosol drug delivery to the nose...
Table 16.8 Risk management matrix for orally inhaled and nasal drug products...
Table 16.9 Summary of FDA attribute tests for aerosols.
Table 16.10 NDA stability protocol.
Table 16.11 Reporting, identification, and qualification thresholds for degr...
Chapter 17
Table 17.1 Advantages and disadvantages of injectable dosage forms.
Table 17.2 Solid‐state physical properties and injectable dosage implication...
Table 17.3 Solution‐ and solid‐state chemical properties and injection dosag...
Table 17.4 Injectable excipient classes and functions.
Table 17.5 Antimicrobial preservatives.
Table 17.6 Standard oxidation potentials for various antioxidants
a
.
Table 17.7 U.S.P. water monographs.
Table 17.8 U.S.P. particulate requirements for injectables.
Table 17.9 Dry heat sterilization and depyrogenation cycles.
Table 17.10 NDA stability protocol.
Chapter 18
Table 18.1 Advantages and disadvantages of topical ocular drug delivery.
Table 18.2 Ophthalmic excipient classes and functions.
Table 18.3 Composition of nepafenac ophthalmic suspension.
Table 18.4 Color coding recommended for topical ophthalmic medications.
Chapter 19
Table 19.1 Advantages and disadvantages of transdermal drug delivery.
Chapter 20
Table 20.1 Advantages and disadvantages of modified‐release drug delivery.
Chapter 27
Table 27.1 Key differences between applications and DMFs.
Table 27.2 Application of the Q7 GMP guidance to API manufacturing.
Table 27.3 Good manufacturing practice guidance for APIs (Q7).
Chapter 30
Table 30.A.1 Conversion of animal doses to human equivalent doses based on b...
Table 30.A.2 Recommended duration of repeated‐dose toxicity studies to suppo...
Table 30.A.3 Recommended duration of repeated‐dose toxicity studies to suppo...
Table 30.A.4 Investigator and sponsor reporting responsibilities.
List of Illustrations
Chapter 1
Figure 1.1 Positive linear relationship between the concentration of aspirin...
Figure 1.2 Exponential decrease in drug blood concentration vs. time....
Figure 1.3 Linear relationship of the natural logarithm of drug blood...
Chapter 3
Figure 3.1 SOA drug‐filter adsorption study. SOA mg/mL concentration after i...
Chapter 7
Figure 7.1 Newtonian flow: the rate of shear versus the shearing force.
Figure 7.2 Viscosity (cP) of some nonprescription products at room temperatu...
Figure 7.3 Rheogram depicting pseudoplastic flow. The
y
‐axis is the shearing...
Figure 7.4 Rate of shear versus. shearing force for a dilatant material.
Figure 7.5 Plastic flow: the shearing rate versus shearing force.
Figure 7.6 Stress versus shear rate rheogram of W
1
/O/W
2
multiple emulsion.
Figure 7.7 A compliance/creep rheogram of a W
1
/O/W
2
multiple emulsion. A con...
Figure 7.8 Oscillatory (dynamic) frequency sweep curve showing the storage m...
Chapter 8
Figure 8.1 Sucrose octaacetate (SOA) concentration remaining versus time for...
Figure 8.2 Sucrose octaacetate (SOA) concentration remaining versus time for...
Figure 8.3 Arrhenius plots for the natural logarithm values of
k
obs
as a fun...
Figure 8.4 Sucrose octaacetate pH‐rate profiles of logarithm values of
k
extr
...
Chapter 9
Figure 9.1 Chord length and sieve particle size frequency polygon distributi...
Figure 9.2 Cumulative frequency percent plot of chord length and sieve parti...
Chapter 12
Figure 12.1 Product design interrelationships among formulation, process, an...
Figure 12.2 Drug development process.
Figure 12.3 Product design decision process following lead candidate selecti...
Chapter 13
Figure 13.1 Tablet formation sequence.
Figure 13.2 Molding for freeze‐dried tablet.
Figure 13.3 Relationships among disintegration, dissolution, and absorption....
Figure 13.4 Rotary tablet press sequence.
Figure 13.5 Oscillating screen/low‐shear granulator.
Figure 13.6 Plastic deformation engineering curve.
Figure 13.7 Cone mill.
Figure 13.8 Cone mill blade configuration.
Figure 13.9 Hammer mill.
Figure 13.10 Pin mill.
Figure 13.11 Fluid energy jet mill.
Figure 13.12 Fluid energy mill in self‐contained clean‐in‐place isolator....
Figure 13.13 V‐blender.
Figure 13.14 Conical screw mixer.
Figure 13.15 Gral high‐shear granulator impeller and chopper.
Figure 13.16 Granulator bowl size and impeller‐tip‐speed relationship.
Figure 13.17 Defined areas within the roller compaction.
Figure 13.18 Fluid‐bed granulator.
Figure 13.19 Compression–time profile.
Figure 13.20 Typical blister strip – top view (a) and blister pack – side vi...
Figure 13.21 Laminates for blister cavities (a) Duplex structure, (b) Triple...
Figure 13.22 Various lidding construction (a) Peelable foil construction, (b...
Figure 13.23 Typical blister packaging assembly process.
Figure 13.A.1 Hygroscopicity classification system.
Chapter 14
Figure 14.1 Encapsulation using a semiautomated capsule machine.
Figure 14.2 Dosator sequence.
Figure 14.3 Dosing disk filling principle.
Figure 14.4
Cpk
evaluation for a 5‐mg capsule % LC. LSL (lower specification...
Figure 14.5
Cpk
evaluation for a 10‐mg capsule % LC. LSL (lower specificatio...
Figure 14.6 Rotary die process for soft gelatin capsules.
Chapter 15
Figure 15.1 DLVO energy interaction curve.
Figure 15.2 Mixer impellers.
Figure 15.3 High‐shear mixer components.
Figure 15.4 Colloid mill.
Figure 15.5 Multiple emulsion.
Figure 15.6 Amphiphilic associations.
Figure 15.7 Liposome structures.
Figure 15.8 Phospholipids and cholesterol structures.
Figure 15.9 Taste score sheet.
Figure 15.10 Ishikawa diagram for formulation and manufacturing design of an...
Chapter 16
Figure 16.1 Respimat soft mist inhaler.
Figure 16.2 Metered‐dose inhaler.
Figure 16.3 Metering valve (inverted).
Figure 16.4 Turbohaler.
Figure 16.5 The Diskus inhaler.
Figure 16.6 Response surface custom design and multicriteria optimization (a...
Figure 16.7 Aerosol product design. Ishikawa fishbone cause and effect diagr...
Chapter 17
Figure 17.1 Freeze‐drying cycle.
Figure 17.2 Freezing of a crystallizing system cycle.
Figure 17.3 Freezing of a noncrystallizing system.
Figure 17.4 Lyophilizer.
Figure 17.5 Steam autoclave.
Figure 17.6 Water vapor pressure–temperature profile.
Figure 17.7 Depyrogenation oven.
Chapter 18
Figure 18.1 Eye anatomy.
Figure 18.2 Sterile manufacturing process for brinzolamide ophthalmic suspen...
Chapter 19
Figure 19.1 Skin anatomy.
Figure 19.2 Steady‐state flux.
Figure 19.3 Cumulative drug permeation.
Figure 19.4 Selected permeation enhancers.
Figure 19.5 Potent combination of penetration enhancers.
Figure 19.6 Various types of transdermal patch systems: (a) Reservoir patch,...
Figure 19.7 Schematic of an iontophoretic drug delivery system.
Figure 19.8 Schematic of the E‐Trans iontophoretic system.
Chapter 20
Figure 20.1 Zero‐order dissolution model.
Figure 20.2 First‐order dissolution model (fraction of drug remaining to be ...
Figure 20.3 Powder compaction and enrobing.
Chapter 24
Figure 24.1 OTC drug facts label.
Chapter 28
Figure 28.1 Qualification model: qualification‐required specifications along...
Chapter 29
Figure 29.1 Pharmaceutical quality system model.
Figure 29.2 Six‐system inspection model.
Figure 29.A.1 Decision Flowchart for Photostability Testing of Drug Products...
Figure 29.A.2 Decision Tree for Data Evaluation for Retest Period or Shelf L...
Chapter 30
Figure 30.A.1 Selection of maximum recommended starting dose for drugs admin...
Guide
Cover Page
Title Page
Copyright Page
Dedication Page
Foreword to Second Edition
Foreword to First Edition
Preface to Second Edition
Preface to First Edition
About the Companion Website
Table of Contents
Begin Reading
Index
Wiley End User License Agreement
Pages
iii
iv
v
xv
xvi
xvii
xviii
xix
xx
1
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
187
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
475
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
508
505
509
506
510
507
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
Integrated Pharmaceutics
Applied Preformulation, Product Design, and Regulatory Science
Second Edition
Antoine Al‐Achi
Campbell University
North Carolina, USA
Mali Ram Gupta
Campbell University
North Carolina, USA
William Craig Stagner
Campbell University
North Carolina, USA
This edition first published 2023© 2023 John Wiley & Sons, Inc.
Edition HistoryJohn Wiley & Sons, Inc. (1e, 2013)
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.
The right of Antoine Al‐Achi, Mali Ram Gupta, and William Craig Stagner to be identified as the authors of this work has been asserted in accordance with law.
Registered Office(s)John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
Editorial OfficeJohn Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA
For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.
Wiley also publishes its books in a variety of electronic formats and by print‐on‐demand. Some content that appears in standard print versions of this book may not be available in other formats.
Limit of Liability/Disclaimer of WarrantyIn view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
Library of Congress Cataloging‐in‐Publication Data applied for:Harback ISBN: 9781119574699
Cover Design and Image: Wiley
To my wife, Pamela Cardella Al‐Achi, and my sons, Elias Gabriel, Anthony William, and John Peter.To my beloved father and mother, Elias and René Nassif Tadros. To my siblings and their families, Peter Al‐Achi, Claudette Martone, and Kamil Al Achi.
To my wife, Sulochna Gupta, and my children and grandchildren, Michael, Saijal, Deepak, Yolanda, Nathan, Maya, and Diago.To my beloved father, Harchand Rai, my mother, Anachi, and the entire Mittal family.
To my wife Nancy, and our children and grandchildren, Ryan, Beth, Ethan; Tripp, Kelly, Amelia; and Justin, Lauren, Henry, Hudson.
To all our students: past, present, and future.
Foreword to Second Edition
The breadth and depth of pharmaceutics is expertly covered by this well‐written and organized second edition of Integrated Pharmaceutics: Applied Preformulation, Product Design, and Regulatory Science. This book should be required reading for educating our next generation of pharmaceutical scientists as it provides up‐to‐date discussion, explanation, relevant examples, and case studies of a plethora of important topics required for both academic and industrial scientists. Part 1, which covers preformulation aspects that must be considered when developing a drug into a product, includes expanded content of such critical concepts as solubility and dissolution, bioavailability and bioequivalence, interfacial properties, adsorption phenomenon, rheological principles, chemical stability and shelf‐life determination, particle science, statistics as related to experimental design, and formulation development concepts. Following in a logical sequence, Part II then provides in‐depth instruction directly related to the design and development of specific dosage forms, including tablets, capsules, dispersed systems (e.g. suspensions, emulsions, colloids), aerosol products (including a helpful section on excipients used in aerosol products), sterile injectable products, ophthalmic products, transdermal products, and oral modified‐release products (including specific examples of coated and matrix modified‐release systems). These chapters will be particularly useful to undergraduate and graduate students in pharmaceutics, pharmacy, and engineering. Lastly, Part III wraps up the book with a comprehensive discussion of the regulatory sciences that every pharmaceutical scientist should have a working knowledge of, including discussion of regulatory practices and guidelines for regulatory agencies around the world, application of regulations for compounding pharmacies, processes involved in IND and NDA drug development studies, regulatory requirements for biological, biosimilar, generic and OTC products, accelerated NDA and expedited access for new therapies, guidance related to drug master files, EU dossiers and API GMP processes, commissioning and qualification, overall quality systems, safety, toxicology and pharmacogenomics studies related to product approval, and discussion of medical devices, combination products, dietary supplements and animal drugs, and devices. It is evident that this second edition provides the reader with important and current aspects of the science involved in successfully developing a pharmaceutical product. As a 35‐year veteran industrial and academic pharmaceutical scientist, I commend the authors for having provided this expertly written and updated contribution to the pharmaceutical sciences.
Robert O. (Bill) Williams III, PhD
Johnson & Johnson Centennial Chair and Professor Division Head, Molecular Pharmaceutics and Drug Delivery
The University of Texas at Austin, College of Pharmacy Editor‐in‐Chief, AAPS PharmSciTech FAAPS, FAIMBE, FNAI
Foreword to First Edition
The wide variety of topics covered by the authors in this book emphasize both the depth and breadth of knowledge needed for pharmaceutical scientists to bring a drug product to the marketplace successfully. The challenge of designing and developing compounds into pharmaceutical products, which are critical to the survival of both the biotech and pharmaceutical industries, will depend largely on the education and extensive training required for young pharmaceutical scientists. This book gives the reader an understanding of the basic and applied sciences involved in the development and approval of a pharmaceutical product through regulatory authorities. Unfortunately, these topics have slowly lost their emphasis over the past several years in graduate courses taught in our colleges of pharmacy.
The eleven chapters in Part I cover preformulation topics, wherein the physical and chemical properties of a drug substance, along with its stability and interactions with excipients and the biological aspects of the formulations, are discussed in detail. These and other preformulation topics covered in this section outline the basic properties that fingerprint both the characteristics of a drug substance and the properties of ingredients that must be considered when formulating a physically and chemically stable dosage form. Part II, Chapters 12 through 20, covers product design topics. The regulatory science aspects of drug development are covered in Chapters 21 through 31. This is yet another area that has received minimal attention in graduate schools.
For both the academic and industrial scientists, and graduate students whose research is focused in this field, the authors have emphasized important aspects of materials science and processing that must be addressed for a successful product introduction following approval through regulatory authorities. The chapters in this book flow extremely well and provide very useful information not only to undergraduate and graduate students in pharmaceutics, pharmacy, materials sciences, and engineering but also to faculty and industrial scientists in these disciplines.
James W. McGinity, PhD
Professor of Pharmaceutics
The University of Texas at Austin
Preface to Second Edition
The second edition of Integrated Pharmaceutics: Applied Preformulation, Product Design, and Regulatory Science expands on the original edition and emphasizes greater integration among the three main sections of the textbook. It is still our intention for the text to deliver valuable material to practitioners, pharmaceutical scientists, and graduate students engaging in research and learning in pharmaceutical sciences in general and pharmaceutics/industrial pharmacy as a major. To that end, this new edition of the book continues to serve those engaged in designing pharmaceutical drug products. The new material added to the second edition reflects suggestions we heard from colleagues and students and the latest trends in the development of dosage forms. While no text can claim complete inclusion of all material on a given subject, the reader of this second edition can find it more comprehensive in its delivered information. The unique integration of regulatory affairs considerations related to product design discussions continues to be featured. While we added newer material to the text, some of the less helpful content was excluded from this edition. Readers may refer to the first edition if they desire to access these omitted topics.
The reader will find that the new edition still contains the basic information that is necessary to formulate a pharmaceutical dosage form. The second edition expands on these topics by making each chapter more comprehensive. Specifically, some of the modifications made on the first edition that are found in this current edition incorporate the following: methods of API solubility enhancement, nonionic, ionic, and acid–base concepts related to solubility and dissolution; interactions involved the drug’s states of matter (solid, liquid, and gas) in a formulation structure and the influence of these interactions on the biological aspects of formulations; liquid–liquid interface, formulation and optimization techniques, and determination of HLB values; data handling in rheometry and the use of rheometry in reverse engineering of a topical dosage form are explored; expanded information on the theoretical aspects of drug stability that include chemical equilibrium theories and applications; particle dimension, types of particle diameter, and the use of particle diameters in formulation development; more examples on statistical analysis, in particular applications related to using JMP® Statistical Discovery Software, Version <14.0>, SAS Institute Inc., Cary, North Carolina in analyzing and interpreting data related to drug development; process analytical technologies (PATs) and scale‐up methodologies; vaccines technology; formulation and process designs, container closure characteristics, various attribute tests, and stability assessment of the final ophthalmic product; FDA inspection and CGMP check list; comparison of regional (EMA, China, FDA, Japan, and WHO) GMP chapters; the recent regulations governing compounding (503A and 505B), USP Chapter 797, compounding sterile preparations, self‐inspection/audit, and a check list (questionnaire); Part 58 (Good laboratory Practice), CGMP for Phase 1 investigational drugs (Guidance for Industry), sterile drug products produced by aseptic processes (CGMP Guidance for Industry), and ICH E6 (R2) Good Clinical Practice; 21 CFR 320 Bioavailability and Bioequivalence requirements as well as development and approval of biosimilars in the USA and EU; Emergency Use Authorization; Orphan Drugs regulations; risk‐based qualifications; Part 820 Quality Systems regulations, Part 820 QSR‐Auditor’s Check List, and Part 11 Electronic Records/Electronic Signature and Auditor’s Check List; GMP guidance (Q7) for APIs. In addition, ICH Q9‐Quality Risk Requirement; pharmacovigilance for medical products and the predictive toxicology roadmap; innovation measures for public health adopted by the FDA and critical path initiatives; Part 601 pertaining to licensing biologicals and Part 610 dealing with general biological products standards; Regulations, CGMPs, and guidance covering medical devices, combination products, dietary supplements, and veterinary drugs and devices as enforced by the regulatory authorities in the USA.
Acknowledgments
All the illustrations and the artwork in this text were produced by Mr. Scott Staton, Production Manager (Pharmaceutical and Educational Research Center; Campbell University). The authors are grateful to his fine contributions and of Ananya Agrawal, BITS Pilani, India, for Appendix 23.A.1. Special thanks go to Mr. Jonathan Rose (Senior Editor, Academic Publishing Group), Ms. Mandy Collison (Managing Editor), and Mr. Sundaramoorthy Balasubramani (Content Refinement Specialist) from Wiley for their excellent professional assistance in publishing this edition. We are appreciative of all the input we have received from colleagues and students concerning the subject matter presented herein.
Antoine Al‐Achi
Mali Ram Gupta
William Craig Stagner
Preface to First Edition
The idea for this book was born out of the authors’ desire to create a textbook to be used for several courses in our pharmaceutical science BS/MS curriculum and cooperative BS/MS engineering/pharmaceutical sciences program approved by North Carolina State University, Raleigh, North Carolina, and Campbell University, Buies Creek, North Carolina. The book will also be used as part of the College of Pharmacy & Health Sciences Pharm.D. program. The book’s theme and scope focus on the application of the principles of physical pharmacy, product design, and regulatory science and how they relate in an intricate web to produce effective dosage forms that deliver drugs to their site of action. Currently, there is a critical shortage of pharmaceutical scientist specialists in product design and related technologies. Historically, most pharmaceutical scientists were educated in pharmacy schools. These programs integrated biology, pharmacology, chemistry, mathematics, physics, and materials science with one overarching goal: drug delivery to treat the human condition. A majority of the Ph.D. pharmaceutical scientists were educated as B.S. pharmacists. Over the past 30 years, pharmacy education has become more drug therapy focused and less drug delivery oriented. Federal funding has also followed this trend, leaving unprecedented shortages of academic pharmaceutical scientists. In addition, the shift in pharmacy education emphasis has required that the pharmaceutical industry hire chemists, biologists, and engineers who do not have the benefit of the integrated educational program that was once offered by schools of pharmacy. These employees are trained (not educated) on the job, although some schools of engineering are trying to fill some of the educational void.
The novel approach of this book is, as much as possible, to integrate international harmonized pharmaceutical development regulatory guidelines and requirements with the science and technology of pharmaceutical product design. New regulatory guidelines such as quality by design, design space analysis, process analytical technology, polymorphism characterization, blend sample uniformity, stability protocols, and the biopharmaceutical classification system are integrated throughout the text. In Part I, we present the fundamentals of physical pharmacy and preformulation as they apply to pharmaceutical dosage form design. Topics such as thermodynamics, drug solubility, drug stability, rheological aspects of formulation, interfacial science, bioavailability, and others are covered in this part. Other chapters cover basic mathematical, statistical, and design‐of‐experiment concepts.
In Part II, we elaborate on the complex multifactorial process that brings together drug delivery to treat a human condition with formulation, manufacturing process, and container closure system design. The inextricable interrelationships among the formulation, the process, and the container closure system are emphasized by integrating each of these product design features into a single dosage‐form chapter. Unification of appropriate preformulation and regulatory science applications is also highlighted. A similar format is incorporated for most chapters: an introduction that discusses the relevant anatomical and bodily function that affect drug delivery, advantages and disadvantages of the product, formulation design that examines dosage‐form‐specific preformulation, excipient compatibility, formulation development; process design, relevant process analytical technologies, pertinent scale‐up models and practices, container closure system design incorporating critical patient and product considerations, risk management, in‐process and final product attribute tests, and new drug application stability assessment programs. Most chapters include extensive reference appendixes of functional excipients, their compendial status, and usage levels. Other reference appendixes include surfactant hydrophile–lipophile balance (HLB) values, oil‐required HLB values, sequestering agent stability constants, lyophilization bulking agents, and eutectic and collapse temperatures.
Part III covers regulations as specified by the U.S. Food and Drug Administration (FDA), European Medicines Agency, and other international regulatory agencies. This part provides a broad spectrum of topics from compliance requirements (current good manufacturing and good laboratory practices, and others), International Conference on Harmonization and other global harmonization initiatives, the investigational new drug (IND) and new drug application (NDA) phase‐appropriate new drug development process, pre‐ and post‐approval processes (INDs, NDAs, abbreviated NDAs, and drug master files), accelerated approval and initiatives for orphan and pediatric drug development, post–drug approval activities, quality system controls, commissioning and qualification (of facilities, equipment, analytical instruments, and test methods, among others), regulatory requirements for all facets of extemporaneous compounding (from handling of prescription for compounding to patient counseling), recommendations for conducting and reporting results of nonclinical and clinical safety and toxicology studies, barriers and benefits of pharmacogenomics studies, to the most recent FDA initiative on regulatory science.
In summary, the book introduces a fresh approach to presenting industrial pharmacy by combining physical pharmacy, product design, and regulatory science issues in a single compendium. The authors hope that the integrated perspective presented will be useful for undergraduate, graduate, and professional pharmacy students and will provide pharmaceutical scientists with a reference resource. The authors will also greatly appreciate feedback and comments that lead to improvements in the book.
Acknowledgments
The authors wish to thank Bob Stagner for reviewing Chapters 12 through 20, 23, 25, and 26 and for providing constructive suggestions, and Paul Johnson for reviewing and providing helpful suggestions on chapters 23 and 29. The authors are also indebted to Drs. Keith Johnson and Larry Gatlin for their expert advice on Chapters 16 and 17, respectively. Special thanks go to Scott Staton for his tireless effort in preparing the excellent illustrations.
The authors appreciate the unwavering support of their department chair, Dr. Emanuel Diliberto. We also acknowledge the help of our graduate students in this endeavor.
Antoine Al‐Achi
Mali Ram Gupta
William Craig Stagner
About the Companion Website
This book is accompanied by a companion website
www.wiley.com/go/Al-Achi/IntegratedPharmaceutics
The website includes:
Study guide
List of equations.
