Co-Crystals in Pharmaceutical Sciences

Inderbir Singh, PhD, is a professor and the Assistant Dean of Research at Chitkara College of Pharmacy, Chitkara University, India. He has published eight books, 25 book chapters, and 180 papers in peer-reviewed journals. He also has 11 utility patents and 15 design registrations under review and has been granted three patents. His research interests include gastroretentive drug delivery systems, biopolymers, biomaterials, modified polymers in drug delivery, pharmaceutical cocrystals, the SeDeM expert system, and 3D printing technology. Subrata Mallick, PhD, is a professor and the Head of the Department of Pharmaceutics in the School of Pharmaceutical Sciences, Siksha ‘O’ Anusandhan University, Odisha, India, with 26 years of teaching, research, and industry experience. He has published over 100 papers in international journals, six books, over 130 conference abstract proceedings, and five scientific articles, in addition to serving as an editorial board member for several international journals. His areas of interest include transdermal drug delivery systems, transmucosal drug delivery systems, powder compaction, drug degradation kinetics and stabilization, and drug-drug and drug-excipient interactions. Ritu Rathi, PhD, is a PhD research scholar at Chitkara College of Pharmacy, Chitkara University, India, with five years of research experience in the field of pharmaceutical sciences. In addition to her active pharmaceutical research, she has published 17 articles and book chapters in various national and international journals, applied for three utility patents, and been granted two design registrations. Her research interests include pharmaceutical cocrystals, solubility enhancement techniques, herbal bioactives, and in-silico modeling techniques.

• Preface xiii1 Pharmaceutical Cocrystals: Introduction, History and Applications 1Oluwatoyin A. Odeku and Olufunke D. Akin-Ajani1.1 Introduction 21.2 History 31.3 Applications of Cocrystals in Pharmaceutical Sciences 41.3.1 Enhanced Solubility 51.3.2 Improved Bioavailability 51.3.3 Stability Enhancement 61.3.4 Taste Masking and Palatability 71.3.5 Controlled Release 81.3.6 Increased Tabletability 81.3.7 Combination Therapy 91.4 Challenges in the Development of Cocrystals 121.5 Marketed Products 171.6 Future of Pharmaceutical Cocrystals 171.7 Conclusion 18Acknowledgment 18References 192 Design and Structural Characteristics of Pharmaceutical Cocrystals 29Harpreet Singh, Bhuvnesh Kumar Singh, Anil Kumar, Arvind Kumar, Arun Kumar Mishra, Ritu Rathi and Inderbir Singh2.1 Introduction 302.1.1 Polymorphism 332.1.2 Salt Cocrystal Continuum 342.2 Design of Pharmaceutical Cocrystals 342.2.1 Molecular Recognition and Supramolecular Interactions 352.2.2 Hansen Solubility Parameters (HSPs) 362.2.3 Coformers Selection and Combinatorial Approaches 372.2.3.1 Theoretical Methods 372.2.3.2 GRAS Coformer Libraries 382.2.3.3 High-Throughput Experimentation 382.2.3.4 Coformer Selection 382.2.4 Combinatorial Approaches 402.3 Structural Characteristics of Pharmaceutical Cocrystals 442.3.1 Crystal Structure Analysis 442.3.2 A Perspective on Cocrystal Hydrogen Bonding 442.3.3 Characterization Techniques 452.4 Challenges and Future Directions in Pharmaceutical Cocrystal 462.5 Conclusion 48Acknowledgment 48References 493 Advancements in Computational Screening Methods for Pharmaceutical Cocrystals 55Maan Singh, Abhishek Mali, Madhukiran Dhondale, Ashish Kumar Agrawal, Amrit Paudel and Dinesh Kumar3.1 Introduction 563.2 Experimental Screening of Cocrystals 593.3 Computational Method for Screening Cocrystals 623.3.1 Molecular Electrostatic Potential Surfaces (MEPS) Measurement 623.3.2 Hirshfeld Surface Analysis (HSA) 663.3.3 Cambridge Structural Database (CSD) 693.3.4 COSMO-RS Approach 723.3.5 Crystal Structure Prediction (CSP) 763.4 Recent Trends in Cocrystal Screening and Future Approach 783.5 Conclusion 81Acknowledgments 82References 824 Preparation Techniques of Pharmaceutical Cocrystals 93Nikita Thakur, Mansi Prashar, Sukhvir Kaur, Neelima Dhingra, Manish Kumar, Ritu Rathi, Inderbir Singh and Poonam Arora4.1 Introduction 944.2 Cocrystal Preparation Techniques 954.2.1 Solid-State Approach 964.2.1.1 Neat-Grinding Method 964.2.1.2 Liquid-Assisted Grinding Method 974.2.1.3 Hot-Melt Extrusion Approach 984.2.2 Solution-Based Method 994.2.2.1 Solvent Evaporation Approach 994.2.2.2 Slurry Conversion Approach 1004.2.2.3 Cooling Crystallization 1014.2.2.4 Antisolvent Method 1024.2.3 Miscellaneous Approaches 1034.2.3.1 Spray Drying and Supercritical CO 2 -Assisted Spray Drying 1034.2.3.2 Twin-Screw Extruder 1044.3 Optimization Parameters for Cocrystal Formation 1084.3.1 Choice of Coformer 1084.3.2 Kinetics of Cocrystallization 1094.3.3 Application of Modeling and Process Analytical Technology 1104.4 Future Perspectives and Challenges 112Acknowledgments 113References 1145 A Brief on Analytical and Characterization Techniques for Evaluation of Pharmaceutical Cocrystals 121Suraj R. Chaudhari, Shashikant B. Bagade, Sonali V. Chaudhari and Atul A. Shirkhedkar5.1 Introduction 1225.2 Analytical Techniques 1235.2.1 X-Ray Powder Diffraction (XRPD) 1235.2.2 Single-Crystal X-Ray Diffraction (SCXRD) 1245.2.3 Differential Scanning Calorimetry (DSC) 1265.2.4 Thermogravimetric Analysis (TGA) 1275.2.5 Spectroscopic Methods (Infra-red, Raman, and Nuclear Magnetic Resonance) 1285.3 Physicochemical Characterization of Cocrystals 1315.3.1 Assessment of Solubility and Dissolution Characteristics 1315.3.2 Cocrystal Stability 1325.3.3 Discussion on Exploration of Analytical Techniques for Characterization of Cocrystals 1335.4 Conclusion 143Acknowledgment 144References 1446 Advancements and Applications of Herbal Cocrystals 153Rajat Goyal, Pankaj Popli, Kashish Wilson, Hitesh Chopra, Sonia Dhiman and Sumeet Gupta6.1 Introduction 1546.1.1 Definition and Overview 1546.1.2 Fundamentals of Cocrystal Formation 1556.1.3 Selection of Coformer 1576.1.4 Methods of Cocrystal Synthesis 1586.1.4.1 Solid-State Methods 1596.1.4.2 Solvent-Based Methods 1606.1.4.3 Solvent Evaporation Method 1606.1.4.4 Miscellaneous Methods 1606.1.5 Characterization Techniques 1616.2 Benefits and Applications of Herbal Cocrystals 1636.2.1 Enhanced Solubility and Bioavailability 1636.2.2 Improved Stability and Shelf Life 1646.3 Challenges and Limitations of Herbal Cocrystals, Solubility Issues, and Incompatibilities 1646.3.1 Scale-Up and Manufacturing Challenges 1646.3.2 Safety Concerns 1656.3.3 Quality Control 1656.3.4 Regulatory Considerations 1666.4 Reported Herbal Cocrystals 1666.5 Future Perspectives and Trends 1666.5.1 Advances in Cocrystal Technology 1666.5.2 Potential for New Herbal Therapeutics 1776.6 Conclusion 178References 1797 Drug-Drug Cocrystals: Advancements and Applications 189Ritu Rathi, Sushant Sharma, Siddhartha Gautham Pal, Rohil Panwar, Taruna, Rakesh Pahwa and Inderbir Singh7.1 Introduction 1907.1.1 Preparation Techniques 1927.1.2 Characterization of DDCS 1967.2 Reported Drug-Drug Cocrystals for Non‐Steroidal Anti-Inflammatory Drugs (NSAIDs) 1997.3 Reported Drug-Drug Cocrystals for Anticancer Drugs 2027.4 Reported Drug-Drug Cocrystals for Antituberculosis Drugs 2067.5 Reported Drug-Drug Cocrystals for Diuretics 2097.6 Reported Drug-Drug Cocrystals for Miscellaneous Drugs 2127.7 Patent Perspectives 2147.8 Marketed Product 2187.9 Conclusion 218Acknowledgment 218References 2198 Scaling Up Pharmaceutical Cocrystals: Exploring Commercial Opportunities and Industrial Prospective 231Kampanart Huanbutta, Tanikan Sangnim, Ritu Rathi and Inderbir Singh8.1 Introduction 2328.2 Challenges and Considerations in Cocrystal Scale-Up 2338.2.1 Process Control and Consistency 2338.2.2 Kinetics of Cocrystallization 2338.2.3 Selection of Appropriate Scale-Up Method 2348.2.4 Regulatory Compliance 2358.3 Promising Methods for Cocrystal Scale-Up 2358.3.1 Solution-Mediated Cocrystallization 2358.3.2 Solid/Slurry Cocrystallization 2408.4 Quality-By-Design Approaches (QbD) in Cocrystallization Manufacturing 2438.5 Process Analytical Technology in Scale-Up Cocrystallization Process 2448.6 Commercial Opportunities for Cocrystals 2468.7 Future Directions and Outlook 2468.7.1 Machine Learning and AI 2468.7.2 Advanced Process Analytical Technology (PAT) 2488.7.3 Green Chemistry 2488.8 Conclusion 249Acknowledgment 250References 2509 Pharmaceutical Cocrystals for Solubility Enhancement of Drugs 257Mouli Das, Sk Habibullah, Tanisha Das and Subrata Mallick9.1 Introduction 2589.2 Why Solubility Enhancement is Important? 2599.3 Factors Affecting Solubility 2609.3.1 Nature of Solute and Solvent 2609.3.2 Particle Size 2609.3.3 Temperature 2619.3.4 Pressure 2619.3.5 Molecular Size 2629.3.6 Polymorphism 2629.3.7 Polarity 2629.3.8 Common-Ion Effect 2629.4 Solubility and Bioavailability 2639.5 Permeability and Cocrystallization 2649.6 Enhancing Solubility through Cocrystallization 2659.6.1 Hot-Melt Extrusion Technique of Cocrystallization to Enhance Solubility 2659.6.2 Amino Acid in Cocrystal to Enhance Solubility 2669.6.3 Polymeric Effect on Cocrystallization 2669.6.4 Cocrystals of Herbal Bioactive to Enhance Solubility 2679.6.5 Solubility Enhancement of Anticancer Drug via Cocrystallization 2729.6.6 Drug-Drug Cocrystallization to Enhance Solubility 2819.6.7 Cocrystallization for Food Encapsulation 2819.7 Conclusion 282Acknowledgment 283References 28310 Pharmaceutical Cocrystals for Improving Physicochemical Properties of Drugs: Enhancement ofTherapeutic Efficacy 293Debabrata Ghosh Dastidar, Arpan Datta, Sanchari Bhattacharya and Moumita Chowdhury10.1 Introduction 29410.2 Preparation and Characterization Methods for Cocrystals 29510.3 Enhancement of Therapeutic Efficacy with Cocrystals 29710.3.1 Improving the Physicochemical Properties of Drugs 30210.3.1.1 Melting Point 30210.3.1.2 Hygroscopicity 30310.3.1.3 Solubility and Dissolution 30310.3.1.4 Mechanical Behavior 30510.3.1.5 Optical Properties 30610.3.2 Enhancing Stability and Shelf Life 30710.3.2.1 Changing the Reaction Cavity/ Environment 30810.3.2.2 Alteration of Solid-State Properties 30910.3.2.3 Manipulation of Hydrogen Bonding Pattern 30910.3.2.4 Influencing Solid-State Microenvironment 31010.3.2.5 Increased Thermal Stability 31110.3.3 Improving Bioavailability and Pharmacokinetics 31210.3.3.1 The Mechanism for Enhancing the Bioavailability and Improve Pharmacokinetics of Drugs 31210.3.4 Combination Therapy 31610.3.5 Improving the Targeted Delivery of Drugs 31810.4 Regulatory Considerations for Cocrystal Approval 31910.5 Conclusion and Future Aspects 322Acknowledgment 323References 32311 Application of Pharmaceutical Cocrystals in Improving Mechanical Properties and Stability 329Sushant Sharma, Ritu Rathi, Ayushi Taneja, Poonam Arora and Inderbir Singh11.1 Introduction 33011.2 Pharmaceutical Cocrystals Improve Mechanical Properties 33211.3 Pharmaceutical Cocrystals Improving Stability 34111.4 Conclusion and Future Prospective 344Acknowledgments 350References 35012 Patents and Regulatory Considerations of Pharmaceutical Cocrystals 357Ritu Rathi, Ritamay Sau, Rakesh K. Sindhu, Harpreet Singh and Inderbir Singh12.1 Introduction 35812.1.1 Comparison Between USFDA and EMA on the Aspects of Cocrystal 36312.2 Generic Concept of Pharmaceutical Cocrystals 36512.3 Data Consideration Using Pharmaceutical Cocrystals for Abridged Application 36712.3.1 Module 3: Quality Aspects for Pharmaceutical Cocrystals 36712.3.1.1 Quality Aspects During Development of Generic Cocrystal API 36912.3.2 Module 4: Non-Clinical Safety Toxicological Studies 36912.3.3 Module 5: Clinical Studies 37012.4 Patent on Cocrystals 37012.5 Conclusion 373Acknowledgment 374References 374Index 379