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

A practical and up-to-date discussion of the formulation and design of dosage forms and delivery systems containing herbal ingredients

In Formulating Pharma-, Nutra-, and Cosmeceutical Products from Herbal Substances: Dosage Forms and Delivery Systems, a team of distinguished researchers delivers a step-by-step approach to preparing and manufacturing dosage forms and delivery systems. Intuitively organized with comprehensive coverage of the fundamentals, functional materials, manufacturing, and marketing of pharmaceutical, nutraceutical, and cosmeceutical products, the book also examines regulatory issues of quality, safety, and efficacy.

The authors discuss essential formulation development and delivery information for novel and controlled delivery systems of herbal ingredients. Readers will also find:

• A thorough introduction to the basic principles of developing modern pharma-, nutra-, and cosmeceutical products from herbal substances
• Comprehensive explorations of conventional formulations, including issues of stability
• Practical discussions of advanced formulations, including chronotherapeutic delivery systems, liposome-based delivery of phytoconstituents, and nanoparticle mediated delivery of herbal actives
• Complete treatments of regulatory challenges, including nonclinical characterization and documentation for marketing authorizations of herbal formulations

Perfect for professionals working in the herbal drug, natural product, and dietary supplement industries, Formulating Pharma-, Nutra-, and Cosmeceutical Products from Herbal Substances will also benefit academic researchers and graduate students studying herbal research, cosmetics, and pharmaceutical sciences.