Formulating Pharma-, Nutra-, and Cosmeceutical Products from Herbal Substances

Anupama Singh, PhD, is Professor and Head of the Department of Pharmacognosy at Sardar Bhagwan Singh University. Hitesh Kulhari, PhD, is an Assistant Professor in the School of Nano Sciences at the Central University of Gujarat. Vikas Anand Saharan, PhD, is Associate Professor and In-charge of the Department of Pharmaceutical Technology (Formulations) at National Institute of Pharmaceutical Education and Research Guwahati (NIPER-G).

• List of Contributors xxxiForeword by Prof. J.M.S. Rana xxxixForeword by Prof. Anil Bhandari xliAbout the Editors xliiiPreface xlvSection I Introduction and Basic Principles 11 From Traditional to Modern Medicine: The Role of Herbs and Phytoconstituents in Pharmaceuticals, Nutraceuticals, and Cosmetics 3Pooja Shah, Surojit Banerjee, Anupama Singh, Hitesh Kulhari, and Vikas Anand Saharan1.1 Introduction 31.2 Traditional Uses of Herbs in Pharmaceuticals, Nutraceuticals, and Cosmeceuticals 51.3 Herbs as a Source of Modern Medicine 171.4 Herbs as a Source of Nutraceuticals/Dietary Supplements 181.5 Herbs as a Source of Cosmeceuticals 181.6 Advantages of Herbal Formulations 241.7 Challenges of Herbal Formulations 331.8 Regulatory Scenario for Herbal Products in Modern Medicine 451.9 Approved Herbal Products 471.10 Conclusion 482 Preparation of Extracts and Their Standardization 75Neeraj K. Sethiya, Garima Agarwal, Samir Bhargava, Vijay S. Rana, Bhavna Kumar, Manmohan Singhal, Dheeraj Bisht, and Umesh K. Patil2.1 Introduction 752.2 Major Parameters 762.3 Minor Parameters 762.4 Important Terminology Used for the Preparation of Extracts and Standardization 762.5 Preparation of Extracts 772.6 Extraction of Plant Material 772.7 Extraction Methods 772.8 Types of Extractions 822.9 Methods of Fractionation and Separation of Phytoconstituents 832.10 Factors Affecting Selection of Extraction Method 832.11 Standardization 832.12 Conclusion 853 Isolation and Purification of Phytoconstituents 91Shreya Sen Sarma, Biswajit Singh, Sushil K. Chaudhary, and Deepak Kumar3.1 Introduction 913.2 Isolation and Purification 923.3 Hyphenated Techniques and Metabolomics 1043.4 Chemical Fingerprinting 1073.5 Bio-Assay-Guided Isolation 1073.6 Conclusion 1084 Natural Polysaccharides for Designing Herbal Formulations 119Saumyadeep Bora, Shuchi Patel, Shreyansh Sharma, Deep Pooja, and Hitesh Kulhari4.1 Introduction 1194.2 Classification of Natural Polysaccharides 1204.3 General Properties and Applications of Important Natural Polysaccharides 1224.4 Conclusion and Future Perspectives 1275 Principles of Sustained, Controlled, and Targeted Delivery of Herbal Actives 139Aseem Setia, Abhishesh K. Mehata, Chandrashekar Singh, Paresh Badgujar, and Madaswamy S. Muthu5.1 Introduction 1395.2 Need for a Drug Delivery System 1405.3 Solubility and Dissolution-Enhanced Drug Delivery Systems 1405.4 Modified-Release Drug Delivery System 1415.5 Types of Modified Drug Delivery Systems 1415.6 Plant Actives and Extracts as a NDDS 1485.7 Drug Delivery Systems of Herbal Actives 1505.8 Targeted Drug Delivery Systems 1545.9 Clinical Trials of Herbal Actives 1555.10 Commercially Available Herbal Actives Drug Delivery System 1565.11 Conclusion and Future Perspective 1566 Formulation and Delivery Issues for Active Ingredients of Herbal Medicines, Nutraceuticals, and Cosmetics: Comparisons to Small-Molecule Drugs 163Monika Ola, Rajveer Bhaskar, Pradeep S. Patil, Sangita V. Badgujar, and Nitin G. Haswani6.1 Introduction 1636.2 Incompatibility Within Formulation 1646.3 Challenges Associated with Herbal Formulations 1676.4 Stability Issues 1696.5 Solubility Issues 1706.6 Permeability Issues 1726.7 Bioavailability and Pharmacokinetics 1726.8 Factors Affecting Bioavailability of Natural Actives 1736.9 Factors Affecting the Pharmacokinetics of Herbal Formulation 1746.10 Modification of Herbal Actives Half-Life 1756.11 Strategies for Modifying the Half-Life of Herbal Actives 1766.12 Enhancement of Bioavailability of Herbal Actives 1776.13 Small Molecules (Synthetic Drugs) Versus Herbal Actives 1806.14 Conclusion 182Section II Conventional Formulations 1937 Stability of Herbal Formulations: Emerging Trends and Techniques 195Dimple S. Lalchandani, Laltanpuii Chenkual, and Pawan K. Porwal7.1 Introduction 1957.2 Importance of Analytical Methods in the Stability Study of Herbal Formulations 1967.3 Challenges Encountered in the Stability Study of Herbal Formulations 1967.4 Analytical Techniques for Estimating the Stability of Herbal Formulations 1977.5 Emerging Trends in Analytical Methods of Herbal Medicine 2077.6 Quality Control and Assurance of Herbal Products 2127.7 Challenges in Quality Assurance of Herbal Medicine 2127.8 Regulatory Basis of Herbal Drug and Stability Testing 2137.9 Conclusion 2148 Fast-Dissolving/-Disintegrating Herbal Dosage Forms 219Debadri Banerjee, Vikas Anand Saharan, and Anupama Singh8.1 Introduction 2198.2 Principles of Disintegration 2208.3 Natural and Synthetic Disintegrants 2218.4 Orally Disintegrating Tablets (ODTs) 2218.5 Orally Disintegrating Films (ODFs) 2298.6 Fast-Disintegrating Pellets 2328.7 Fast-Dissolving/-Disintegrating Dosage Forms of Phytoconstituents 2338.8 Challenges 2348.9 Clinical Trials 2358.10 Marketed Formulation 2368.11 Conclusion 2369 Herbal Formulations for Transmucosal Drug Delivery 243Debadri Banerjee, Vikas Anand Saharan, and Anupama Singh9.1 Introduction 2439.2 Mucoadhesion 2439.3 Transcellular and Paracellular Permeation 2469.4 Various Transmucosal Routes: Drug Delivery Aspects 2479.5 Phytochemical Delivery Through Transmucosal Route 2579.6 Challenges 2589.7 Clinical Trials 2619.8 Marketed Herbal Mucoadhesive Products 2619.9 Conclusion 26110 Solid Dispersions 271Kirti Shirsath, Indrani Maji, Srushti Mahajan, Mayur Aalhate, Ujala Gupta, and Pankaj K. Singh10.1 Introduction 27110.2 Components for Solid Dispersion-Based Formulations 27310.3 Physiological Principle Behind Drug Absorption 27610.4 Methods of Preparation 27710.5 Characterization of Solid Dispersion 28110.6 Drug Delivery Applications 28310.7 Challenges in the Extraction of Phytoconstituent 28610.8 Conclusion 28711 Formulating Pharma-, Nutra-, and Cosmeceutical Products from Herbal Substances 299Pooja Khairnar, Tejaswini Kolipaka, Giriraj Pandey, Vivek Phatale, Aachal Hedaoo, and Saurabh Srivastava11.1 Introduction 29911.2 Challenges for the Delivery of Herbal Actives 30011.3 Rationale for Pelletization 30011.4 Ideal Characteristics and Advantages of Pelletization of Herbal Actives 30111.5 Phenomenon of Pelletization 30211.6 Pelletization Techniques 30311.7 Characterization of Pellets 30611.8 Delivery Aspects of Pellets for Herbal Actives 30911.9 Regulatory Considerations Toward Clinical Translation 31411.10 Marketed Products 31611.11 Conclusion and Future Perspective 31612 Hydrogels as Delivery Systems in Herbal Medicine 323Khushi Rode, Nandkishor Rajankar, Mayur Aalhate, Srushti Mahajan, Indrani Maji, Ujala Gupta, and Pankaj K. Singh12.1 Introduction 32312.2 Application of Hydrogels 32412.3 Benefits of Hydrogels in Delivering Herbal Medicine 32612.4 Hydrogels as an Effective Delivery of Nanocarrier System 33012.5 Modification in Hydrogel Properties to Effectively Deliver Herbal Medicine 33512.6 Formulation of Hydrogels to Precisely Deliver Herbal Medicine 34212.7 Challenges Associated with the Delivery of Hydrogels 34312.8 Conclusion and Future Prospects 34413 Emulsions and Self-Emulsifying Delivery Systems for Herbal Actives 355Puja Tripathy, Raju Barman, Rinku Baishya, and Deepak Kumar13.1 Introduction 35513.2 Emulsions 35613.3 Composition of Emulsion 35713.4 Thermodynamics of EMs 35813.5 Preparation Methods 35913.6 Characterization of Emulsions 36213.7 Optimization of Emulsions 36313.8 Herbal-Active Loaded Emulsions 36413.9 Clinical Studies 36413.10 Conclusion and Future Perspectives 371Section III Advanced Formulations 37914 Chronotherapeutic Delivery Systems 381Akanksha Chaturvedi, Priyanka Arora, and Rahul Shukla14.1 Introduction 38114.2 Principles of Biological Clock 38214.3 Need for a Chronotherapeutic Drug Delivery System 38314.4 Mechanisms of Chronotherapeutic Drug Delivery Systems 38414.5 Development of Chronotherapeutic Delivery Systems 38414.6 Technological Advancement in Chronotherapeutic Drug Delivery Systems 38614.7 Phytomedicine-Loaded Chronotherapeutic Drug Delivery Systems in Therapeutic Intervention 38814.8 Chinese Herbal Medicines-Incorporated Chronotherapeutic Drug Delivery Systems 39114.9 Herbal Excipients Modulating Chronotherapeutic Drug Delivery Systems 39114.10 Clinical Translation and Patented Chronotherapeutic Drug Delivery Systems-Based Formulations 39214.11 Challenges/Hurdles in Chonopharmaceutical Drug Research and Development 39314.12 Conclusion and Future Perspectives 39515 Liposomes-Based Delivery of Phytoconstituents 399Shuchi Patel, Mahima Jadav, Deepali Sammal, Hitesh Kulhari, and Deep Pooja15.1 Introduction 39915.2 Types of Liposomes 39915.3 Preparation of Liposomes by Different Methods 40115.4 Delivery of Phytoconstituents Using Liposomes 40315.5 Conclusion 41216 Nanoparticles-Mediated Delivery of Herbal Actives 419Priyanka Dubey, Shivangi Bharadwaj, Shruti Richa, Kajal Kumari, Payal Khesarwani, and Swapnil Sharma16.1 Introduction 41916.2 General Principles of Nanoparticle-Mediated Herbal Actives 42016.3 Types of Herbal Nanoformulations 42216.4 Methods of Preparation for Herbal Active Nanoformulations 43216.5 NPs Mediated Delivery of Herbal Actives to Treat Different Diseases 43516.6 New Approaches, Challenges, and Limitations of Herbal-Mediated Nanoformulation 43916.7 Clinical Trials and US Food and Drug Administration-Approved Herbal Active Nanoformulations 44216.8 Conclusion and Future Prospective 44217 Herbal Extracts and Phytoconstituents-Loaded Transferosomes, Ethosomes, and Transdermal Patches in Drug Delivery 453Nirmal Morya, Keshav Hirave, Debadri Banerjee, Anupama Singh, and Vikas Anand Saharan17.1 Introduction 45317.2 Delivery Aspects 45417.3 Transferosomes 45617.4 Ethosomes 46617.5 Transdermal Patches 47617.6 Challenges in Herbal Active Delivery 48617.7 Conclusion 48618 Dendrimers as Nanocarriers for Phytoceuticals 495Surojit Banerjee, Keshav Hirave, Deep Pooja, Hitesh Kulhari, Anupama Singh, and Vikas Anand Saharan18.1 Introduction 49518.2 Principles of Dendrimers 49618.3 Types of Dendrimers 49918.4 Dendrimer Formulations 50418.5 Preparation Process 50818.6 Toxicity of Dendrimers 51118.7 Challenges for Herbal Actives 51418.8 Examples of Dendrimer-Based Delivery of Phytoconstituents 51718.9 Preclinical Studies 51718.10 Conclusion 52319 Applications of Carbon-Based Nanomaterials for the Delivery of Herbal Molecules 533Saumyadeep Bora, Deep Pooja, Brahmaji R. Mutyala, and Hitesh Kulhari19.1 Introduction 53319.2 Properties of Herbal Molecules 53419.3 Challenges Associated with the Delivery of Herbal Molecules 53519.4 Role of Nanocarriers in Herbal Molecule Delivery 53619.5 Characteristics of Carbon-Based Nanomaterials for Herbal Molecule Delivery 53719.6 Classification of Carbon-Based Nanomaterials 53719.7 Applications of Carbon-Based Nanomaterials in Herbal Molecule Delivery 53919.8 Conclusion and Future Perspectives 54220 Phytoconstituents and Plant Extract-Based Formulations for Wound Healing 549Keshav Hirave, Nirmal Morya, Surojit Banerjee, Anupama Singh, and Vikas Anand Saharan20.1 Introduction 54920.2 Mechanism of Wound Healing 55020.3 Wound Classification 55320.4 Factors Affecting Wound Healing 55420.5 Nanocarrier in Wound Dressing 55620.6 Medicinal Plants in Wound Healing/Plant Extracts, Extract Fractions and Phytoconstituent and Plant Extract Used in Wound Healing 55620.7 Plant-Derived Phytoconstituent and Extract-Based Formulation for Wound Healing 56720.8 Clinical Trials 57320.9 Role of Different Plants in Wound Healing 57320.10 Marketed Formulations/Commercial Products 58420.11 Some Patented Innovations in Wound Healing 58520.12 Future Directions and Challenges 58520.13 Conclusion 58921 Chemo-Herbal Combination Drug Delivery for Cancer Management 599Shivangi Bharadwaj, Priyanka Dubey, Shruti Richa, Kajal Kumari, Payal Kesarwani, Kanika Verma, and Swapnil Sharma21.1 Introduction 59921.2 Challenges in Targeting Chemo-Herbal Drugs: Overcoming Physicochemical, Biological, and Physiological Barriers for Effective Drug Delivery 60121.3 Optimizing Drug Delivery Strategies for Chemo-herbal Drugs: Overcoming Barriers and Enhancing Therapeutic Efficacy with Effective Targeting 60221.4 Delivery Aspects of Chemo-Herbal Formulation in Cancer Therapy 61421.5 Clinical Trials of Chemo-Herbal Formulations 62121.6 Conclusion and Future Perspective 62422 Protein Nanocarriers for the Delivery of Phytoconstituents 633Ngangom Bidyarani, Kulandaivelu Velmourougane, Umesh Kumar, and Radha Prasanna22.1 Introduction 63322.2 Protein Nanocarriers 63322.3 Methods of Preparation of Protein-Based Nanocarriers 63422.4 Protein Nanocarriers for Phytoconstituents Delivery 63522.5 Prospects of Nanotechnology for Delivery Purposes 63722.6 Current Scenario and the Path Ahead 63822.7 Conclusions 638Section IV Regulatory Challenges 64323 Nonclinical Characterization and Documentation for Marketing Authorizations of Herbal Formulations 645Swati Dobhal, Nitish S. Jangwan, Shradha Bisht, Vikas Anand Saharan, and Mamta F. Singh23.1 Introduction 64523.2 Nonclinical Characterization of Herbal Formulations: Pharmacodynamics, Toxicology and Pharmacokinetic Studies 64623.3 Regulatory Approvals for Marketing Herbal Formulations: A Global Overview of Documentation Requirements 65223.4 Challenges 66823.5 Conclusion 66924 Quality Challenge in Regulatory Approval of Medicinal Products Containing Combinations of Herbal Substances 677Siddheshwar Kisan Chauthe, Soham Rajyaguru, Aditi Puranik, Nishi Yadao, and Kajal Rathod24.1 Introduction to Phytomedicines 67724.2 Classification of Herbal Medicines Based on Regulatory Frameworks and Standards 67824.3 Quality Challenges Related to Herbal Medicines 67924.4 Global Regulatory Landscape of Herbal Medicines 68424.5 WHO Regulatory Guidelines on GMP, GACP and Quality Control of Herbal Medicines 69024.6 Development and Standardization of Herbal Medicines 69524.7 Challenges in the Development of Herbal Medicines 69624.8 Conclusion 69725 Evidence-Based Clinical Assessment of Herbal Formulations: Traditional and Modern Insights 703Debadri Banerjee, Surojit Banerjee, Pooja Shah, Anupama Singh, and Vikas Anand Saharan25.1 Introduction 70325.2 Indian Traditional Medicine 70425.3 Modern Herbal Medicine 70625.4 Regulatory Guidelines 70825.5 Validation Approaches and Clinical Assessments 71325.6 Obstacles to Clinical Assessment of Herbal Formulations 71625.7 Conclusion 732References 73326 Patient Safety Issues with Herbal Substances and Formulations 743Deepali Sammal, Saumyadeep Bora, Hitesh Kulhari, and Deep PoojaObjectives 74326.1 Introduction 74326.2 World Health Organization Regulatory Guidelines for Safety of Herbal Medicines 74426.3 European Guidelines for the Herbal Medicines 74526.4 Indian Regulations for Herbal Medicines 74626.5 USFDA Guidelines for Herbal Medicines 74626.6 Safety of Herbal Medicinal Products 74726.7 Hepatotoxicity Caused by Herbal Medicines 74826.8 Nephrotoxicity Induced by Herbal Drug Medicines 74926.9 Genotoxicity Induced by Herbal Drug Medicines 74926.10 Other Toxicities Induced by Herbal Drug Medicines 75026.11 Conclusion 750Acknowledgment 750References 750Index 753