List of Contributors xxxi
Foreword by Prof. J.M.S. Rana xxxix
Foreword by Prof. Anil Bhandari xli
About the Editors xliii
Preface xlv
Section I Introduction and Basic Principles 1
1 From Traditional to Modern Medicine: The Role of Herbs and Phytoconstituents in Pharmaceuticals, Nutraceuticals, and Cosmetics 3
Pooja Shah, Surojit Banerjee, Anupama Singh, Hitesh Kulhari, and Vikas Anand Saharan
1.1 Introduction 3
1.2 Traditional Uses of Herbs in Pharmaceuticals, Nutraceuticals, and Cosmeceuticals 5
1.3 Herbs as a Source of Modern Medicine 17
1.4 Herbs as a Source of Nutraceuticals/Dietary Supplements 18
1.5 Herbs as a Source of Cosmeceuticals 18
1.6 Advantages of Herbal Formulations 24
1.7 Challenges of Herbal Formulations 33
1.8 Regulatory Scenario for Herbal Products in Modern Medicine 45
1.9 Approved Herbal Products 47
1.10 Conclusion 48
2 Preparation of Extracts and Their Standardization 75
Neeraj K. Sethiya, Garima Agarwal, Samir Bhargava, Vijay S. Rana, Bhavna Kumar, Manmohan Singhal, Dheeraj Bisht, and Umesh K. Patil
2.1 Introduction 75
2.2 Major Parameters 76
2.3 Minor Parameters 76
2.4 Important Terminology Used for the Preparation of Extracts and Standardization 76
2.5 Preparation of Extracts 77
2.6 Extraction of Plant Material 77
2.7 Extraction Methods 77
2.8 Types of Extractions 82
2.9 Methods of Fractionation and Separation of Phytoconstituents 83
2.10 Factors Affecting Selection of Extraction Method 83
2.11 Standardization 83
2.12 Conclusion 85
3 Isolation and Purification of Phytoconstituents 91
Shreya Sen Sarma, Biswajit Singh, Sushil K. Chaudhary, and Deepak Kumar
3.1 Introduction 91
3.2 Isolation and Purification 92
3.3 Hyphenated Techniques and Metabolomics 104
3.4 Chemical Fingerprinting 107
3.5 Bio-Assay-Guided Isolation 107
3.6 Conclusion 108
4 Natural Polysaccharides for Designing Herbal Formulations 119
Saumyadeep Bora, Shuchi Patel, Shreyansh Sharma, Deep Pooja, and Hitesh Kulhari
4.1 Introduction 119
4.2 Classification of Natural Polysaccharides 120
4.3 General Properties and Applications of Important Natural Polysaccharides 122
4.4 Conclusion and Future Perspectives 127
5 Principles of Sustained, Controlled, and Targeted Delivery of Herbal Actives 139
Aseem Setia, Abhishesh K. Mehata, Chandrashekar Singh, Paresh Badgujar, and Madaswamy S. Muthu
5.1 Introduction 139
5.2 Need for a Drug Delivery System 140
5.3 Solubility and Dissolution-Enhanced Drug Delivery Systems 140
5.4 Modified-Release Drug Delivery System 141
5.5 Types of Modified Drug Delivery Systems 141
5.6 Plant Actives and Extracts as a NDDS 148
5.7 Drug Delivery Systems of Herbal Actives 150
5.8 Targeted Drug Delivery Systems 154
5.9 Clinical Trials of Herbal Actives 155
5.10 Commercially Available Herbal Actives Drug Delivery System 156
5.11 Conclusion and Future Perspective 156
6 Formulation and Delivery Issues for Active Ingredients of Herbal Medicines, Nutraceuticals, and Cosmetics: Comparisons to Small-Molecule Drugs 163
Monika Ola, Rajveer Bhaskar, Pradeep S. Patil, Sangita V. Badgujar, and Nitin G. Haswani
6.1 Introduction 163
6.2 Incompatibility Within Formulation 164
6.3 Challenges Associated with Herbal Formulations 167
6.4 Stability Issues 169
6.5 Solubility Issues 170
6.6 Permeability Issues 172
6.7 Bioavailability and Pharmacokinetics 172
6.8 Factors Affecting Bioavailability of Natural Actives 173
6.9 Factors Affecting the Pharmacokinetics of Herbal Formulation 174
6.10 Modification of Herbal Actives Half-Life 175
6.11 Strategies for Modifying the Half-Life of Herbal Actives 176
6.12 Enhancement of Bioavailability of Herbal Actives 177
6.13 Small Molecules (Synthetic Drugs) Versus Herbal Actives 180
6.14 Conclusion 182
Section II Conventional Formulations 193
7 Stability of Herbal Formulations: Emerging Trends and Techniques 195
Dimple S. Lalchandani, Laltanpuii Chenkual, and Pawan K. Porwal
7.1 Introduction 195
7.2 Importance of Analytical Methods in the Stability Study of Herbal Formulations 196
7.3 Challenges Encountered in the Stability Study of Herbal Formulations 196
7.4 Analytical Techniques for Estimating the Stability of Herbal Formulations 197
7.5 Emerging Trends in Analytical Methods of Herbal Medicine 207
7.6 Quality Control and Assurance of Herbal Products 212
7.7 Challenges in Quality Assurance of Herbal Medicine 212
7.8 Regulatory Basis of Herbal Drug and Stability Testing 213
7.9 Conclusion 214
8 Fast-Dissolving/-Disintegrating Herbal Dosage Forms 219
Debadri Banerjee, Vikas Anand Saharan, and Anupama Singh
8.1 Introduction 219
8.2 Principles of Disintegration 220
8.3 Natural and Synthetic Disintegrants 221
8.4 Orally Disintegrating Tablets (ODTs) 221
8.5 Orally Disintegrating Films (ODFs) 229
8.6 Fast-Disintegrating Pellets 232
8.7 Fast-Dissolving/-Disintegrating Dosage Forms of Phytoconstituents 233
8.8 Challenges 234
8.9 Clinical Trials 235
8.10 Marketed Formulation 236
8.11 Conclusion 236
9 Herbal Formulations for Transmucosal Drug Delivery 243
Debadri Banerjee, Vikas Anand Saharan, and Anupama Singh
9.1 Introduction 243
9.2 Mucoadhesion 243
9.3 Transcellular and Paracellular Permeation 246
9.4 Various Transmucosal Routes: Drug Delivery Aspects 247
9.5 Phytochemical Delivery Through Transmucosal Route 257
9.6 Challenges 258
9.7 Clinical Trials 261
9.8 Marketed Herbal Mucoadhesive Products 261
9.9 Conclusion 261
10 Solid Dispersions 271
Kirti Shirsath, Indrani Maji, Srushti Mahajan, Mayur Aalhate, Ujala Gupta, and Pankaj K. Singh
10.1 Introduction 271
10.2 Components for Solid Dispersion-Based Formulations 273
10.3 Physiological Principle Behind Drug Absorption 276
10.4 Methods of Preparation 277
10.5 Characterization of Solid Dispersion 281
10.6 Drug Delivery Applications 283
10.7 Challenges in the Extraction of Phytoconstituent 286
10.8 Conclusion 287
11 Formulating Pharma-, Nutra-, and Cosmeceutical Products from Herbal Substances 299
Pooja Khairnar, Tejaswini Kolipaka, Giriraj Pandey, Vivek Phatale, Aachal Hedaoo, and Saurabh Srivastava
11.1 Introduction 299
11.2 Challenges for the Delivery of Herbal Actives 300
11.3 Rationale for Pelletization 300
11.4 Ideal Characteristics and Advantages of Pelletization of Herbal Actives 301
11.5 Phenomenon of Pelletization 302
11.6 Pelletization Techniques 303
11.7 Characterization of Pellets 306
11.8 Delivery Aspects of Pellets for Herbal Actives 309
11.9 Regulatory Considerations Toward Clinical Translation 314
11.10 Marketed Products 316
11.11 Conclusion and Future Perspective 316
12 Hydrogels as Delivery Systems in Herbal Medicine 323
Khushi Rode, Nandkishor Rajankar, Mayur Aalhate, Srushti Mahajan, Indrani Maji, Ujala Gupta, and Pankaj K. Singh
12.1 Introduction 323
12.2 Application of Hydrogels 324
12.3 Benefits of Hydrogels in Delivering Herbal Medicine 326
12.4 Hydrogels as an Effective Delivery of Nanocarrier System 330
12.5 Modification in Hydrogel Properties to Effectively Deliver Herbal Medicine 335
12.6 Formulation of Hydrogels to Precisely Deliver Herbal Medicine 342
12.7 Challenges Associated with the Delivery of Hydrogels 343
12.8 Conclusion and Future Prospects 344
13 Emulsions and Self-Emulsifying Delivery Systems for Herbal Actives 355
Puja Tripathy, Raju Barman, Rinku Baishya, and Deepak Kumar
13.1 Introduction 355
13.2 Emulsions 356
13.3 Composition of Emulsion 357
13.4 Thermodynamics of EMs 358
13.5 Preparation Methods 359
13.6 Characterization of Emulsions 362
13.7 Optimization of Emulsions 363
13.8 Herbal-Active Loaded Emulsions 364
13.9 Clinical Studies 364
13.10 Conclusion and Future Perspectives 371
Section III Advanced Formulations 379
14 Chronotherapeutic Delivery Systems 381
Akanksha Chaturvedi, Priyanka Arora, and Rahul Shukla
14.1 Introduction 381
14.2 Principles of Biological Clock 382
14.3 Need for a Chronotherapeutic Drug Delivery System 383
14.4 Mechanisms of Chronotherapeutic Drug Delivery Systems 384
14.5 Development of Chronotherapeutic Delivery Systems 384
14.6 Technological Advancement in Chronotherapeutic Drug Delivery Systems 386
14.7 Phytomedicine-Loaded Chronotherapeutic Drug Delivery Systems in Therapeutic Intervention 388
14.8 Chinese Herbal Medicines-Incorporated Chronotherapeutic Drug Delivery Systems 391
14.9 Herbal Excipients Modulating Chronotherapeutic Drug Delivery Systems 391
14.10 Clinical Translation and Patented Chronotherapeutic Drug Delivery Systems-Based Formulations 392
14.11 Challenges/Hurdles in Chonopharmaceutical Drug Research and Development 393
14.12 Conclusion and Future Perspectives 395
15 Liposomes-Based Delivery of Phytoconstituents 399
Shuchi Patel, Mahima Jadav, Deepali Sammal, Hitesh Kulhari, and Deep Pooja
15.1 Introduction 399
15.2 Types of Liposomes 399
15.3 Preparation of Liposomes by Different Methods 401
15.4 Delivery of Phytoconstituents Using Liposomes 403
15.5 Conclusion 412
16 Nanoparticles-Mediated Delivery of Herbal Actives 419
Priyanka Dubey, Shivangi Bharadwaj, Shruti Richa, Kajal Kumari, Payal Khesarwani, and Swapnil Sharma
16.1 Introduction 419
16.2 General Principles of Nanoparticle-Mediated Herbal Actives 420
16.3 Types of Herbal Nanoformulations 422
16.4 Methods of Preparation for Herbal Active Nanoformulations 432
16.5 NPs Mediated Delivery of Herbal Actives to Treat Different Diseases 435
16.6 New Approaches, Challenges, and Limitations of Herbal-Mediated Nanoformulation 439
16.7 Clinical Trials and US Food and Drug Administration-Approved Herbal Active Nanoformulations 442
16.8 Conclusion and Future Prospective 442
17 Herbal Extracts and Phytoconstituents-Loaded Transferosomes, Ethosomes, and Transdermal Patches in Drug Delivery 453
Nirmal Morya, Keshav Hirave, Debadri Banerjee, Anupama Singh, and Vikas Anand Saharan
17.1 Introduction 453
17.2 Delivery Aspects 454
17.3 Transferosomes 456
17.4 Ethosomes 466
17.5 Transdermal Patches 476
17.6 Challenges in Herbal Active Delivery 486
17.7 Conclusion 486
18 Dendrimers as Nanocarriers for Phytoceuticals 495
Surojit Banerjee, Keshav Hirave, Deep Pooja, Hitesh Kulhari, Anupama Singh, and Vikas Anand Saharan
18.1 Introduction 495
18.2 Principles of Dendrimers 496
18.3 Types of Dendrimers 499
18.4 Dendrimer Formulations 504
18.5 Preparation Process 508
18.6 Toxicity of Dendrimers 511
18.7 Challenges for Herbal Actives 514
18.8 Examples of Dendrimer-Based Delivery of Phytoconstituents 517
18.9 Preclinical Studies 517
18.10 Conclusion 523
19 Applications of Carbon-Based Nanomaterials for the Delivery of Herbal Molecules 533
Saumyadeep Bora, Deep Pooja, Brahmaji R. Mutyala, and Hitesh Kulhari
19.1 Introduction 533
19.2 Properties of Herbal Molecules 534
19.3 Challenges Associated with the Delivery of Herbal Molecules 535
19.4 Role of Nanocarriers in Herbal Molecule Delivery 536
19.5 Characteristics of Carbon-Based Nanomaterials for Herbal Molecule Delivery 537
19.6 Classification of Carbon-Based Nanomaterials 537
19.7 Applications of Carbon-Based Nanomaterials in Herbal Molecule Delivery 539
19.8 Conclusion and Future Perspectives 542
20 Phytoconstituents and Plant Extract-Based Formulations for Wound Healing 549
Keshav Hirave, Nirmal Morya, Surojit Banerjee, Anupama Singh, and Vikas Anand Saharan
20.1 Introduction 549
20.2 Mechanism of Wound Healing 550
20.3 Wound Classification 553
20.4 Factors Affecting Wound Healing 554
20.5 Nanocarrier in Wound Dressing 556
20.6 Medicinal Plants in Wound Healing/Plant Extracts, Extract Fractions and Phytoconstituent and Plant Extract Used in Wound Healing 556
20.7 Plant-Derived Phytoconstituent and Extract-Based Formulation for Wound Healing 567
20.8 Clinical Trials 573
20.9 Role of Different Plants in Wound Healing 573
20.10 Marketed Formulations/Commercial Products 584
20.11 Some Patented Innovations in Wound Healing 585
20.12 Future Directions and Challenges 585
20.13 Conclusion 589
21 Chemo-Herbal Combination Drug Delivery for Cancer Management 599
Shivangi Bharadwaj, Priyanka Dubey, Shruti Richa, Kajal Kumari, Payal Kesarwani, Kanika Verma, and Swapnil Sharma
21.1 Introduction 599
21.2 Challenges in Targeting Chemo-Herbal Drugs: Overcoming Physicochemical, Biological, and Physiological Barriers for Effective Drug Delivery 601
21.3 Optimizing Drug Delivery Strategies for Chemo-herbal Drugs: Overcoming Barriers and Enhancing Therapeutic Efficacy with Effective Targeting 602
21.4 Delivery Aspects of Chemo-Herbal Formulation in Cancer Therapy 614
21.5 Clinical Trials of Chemo-Herbal Formulations 621
21.6 Conclusion and Future Perspective 624
22 Protein Nanocarriers for the Delivery of Phytoconstituents 633
Ngangom Bidyarani, Kulandaivelu Velmourougane, Umesh Kumar, and Radha Prasanna
22.1 Introduction 633
22.2 Protein Nanocarriers 633
22.3 Methods of Preparation of Protein-Based Nanocarriers 634
22.4 Protein Nanocarriers for Phytoconstituents Delivery 635
22.5 Prospects of Nanotechnology for Delivery Purposes 637
22.6 Current Scenario and the Path Ahead 638
22.7 Conclusions 638
Section IV Regulatory Challenges 643
23 Nonclinical Characterization and Documentation for Marketing Authorizations of Herbal Formulations 645
Swati Dobhal, Nitish S. Jangwan, Shradha Bisht, Vikas Anand Saharan, and Mamta F. Singh
23.1 Introduction 645
23.2 Nonclinical Characterization of Herbal Formulations: Pharmacodynamics, Toxicology and Pharmacokinetic Studies 646
23.3 Regulatory Approvals for Marketing Herbal Formulations: A Global Overview of Documentation Requirements 652
23.4 Challenges 668
23.5 Conclusion 669
24 Quality Challenge in Regulatory Approval of Medicinal Products Containing Combinations of Herbal Substances 677
Siddheshwar Kisan Chauthe, Soham Rajyaguru, Aditi Puranik, Nishi Yadao, and Kajal Rathod
24.1 Introduction to Phytomedicines 677
24.2 Classification of Herbal Medicines Based on Regulatory Frameworks and Standards 678
24.3 Quality Challenges Related to Herbal Medicines 679
24.4 Global Regulatory Landscape of Herbal Medicines 684
24.5 WHO Regulatory Guidelines on GMP, GACP and Quality Control of Herbal Medicines 690
24.6 Development and Standardization of Herbal Medicines 695
24.7 Challenges in the Development of Herbal Medicines 696
24.8 Conclusion 697
25 Evidence-Based Clinical Assessment of Herbal Formulations: Traditional and Modern Insights 703
Debadri Banerjee, Surojit Banerjee, Pooja Shah, Anupama Singh, and Vikas Anand Saharan
25.1 Introduction 703
25.2 Indian Traditional Medicine 704
25.3 Modern Herbal Medicine 706
25.4 Regulatory Guidelines 708
25.5 Validation Approaches and Clinical Assessments 713
25.6 Obstacles to Clinical Assessment of Herbal Formulations 716
25.7 Conclusion 732
References 733
26 Patient Safety Issues with Herbal Substances and Formulations 743
Deepali Sammal, Saumyadeep Bora, Hitesh Kulhari, and Deep Pooja
Objectives 743
26.1 Introduction 743
26.2 World Health Organization Regulatory Guidelines for Safety of Herbal Medicines 744
26.3 European Guidelines for the Herbal Medicines 745
26.4 Indian Regulations for Herbal Medicines 746
26.5 USFDA Guidelines for Herbal Medicines 746
26.6 Safety of Herbal Medicinal Products 747
26.7 Hepatotoxicity Caused by Herbal Medicines 748
26.8 Nephrotoxicity Induced by Herbal Drug Medicines 749
26.9 Genotoxicity Induced by Herbal Drug Medicines 749
26.10 Other Toxicities Induced by Herbal Drug Medicines 750
26.11 Conclusion 750
Acknowledgment 750
References 750
Index 753
