Drug Development Approaches for Poorly Soluble Compounds

Dr. Yogeshwar Bachhav is a distinguished pharmaceutical professional with over 19 years of experience in drug development, spanning R&D, CMC, regulatory strategy, and business development. From his previous experiences working at Pantec Biosolutions AG (Liechtenstein), DebioPharm (Switzerland), AiCuris (Germany) and as a founder and Director of Adex Pharma, to date he has successfully contributed to the CMC development of several drug candidates from discovery to clinical and commercial phases. Currently, he also serves as an Independent Consultant at AiCuris Anti-infective Cures AG, Germany, leading formulation design, outsourcing, and regulatory documentation (IMPD/IND, ANDA) across global markets. Dr. Bachhav holds M.Pharm in Pharmaceutical Chemistry and PhD in Pharmaceutics from ICT (Mumbai), an LL.B from the University of Mumbai, and a Global MBA from the University of Western Australia, along with an Advanced Business Management certification from IIM Kozhikode. With 19 peer-reviewed publications, 7 international patents, more than 50 invited talks globally and as an editor of 3 books, Dr. Bachhav continues to advance pharmaceutical innovation through his deep scientific expertise and strategic leadership.

• Series Editors Preface xviiPreface xix1 Impact of Poor Solubility on Drug Development 1Preshita Desai1.1 Introduction 11.2 Drug Solubility 21.3 Impact of Poor Drug Solubility on Drug-Like Properties 41.4 Addressing Poor Drug Solubility Challenge 51.5 Poor Drug Solubility—Is It Always a Challenge? 131.6 Conclusion 142 Design and Development of Amorphous Solid Dispersion as Enabling Formulation Strategies of Poorly Soluble Drugs 19Amrit Paudel and Sarah Stryeck2.1 Basics of Amorphous Solid Dispersion (ASD) 192.2 Analytical Characterization of ASDs 282.3 Preformulation and Screening of ASD 382.4 Manufacturing Processes of ASD 402.5 Biopharmaceutics of ASD 462.6 Stability Considerations of ASD 502.7 Computational Tools for ASD Development 542.8 Emerging Innovations in ASD 593 Nanosizing of Drugs to Improve the Apparent Dissolution and Bioavailability 81Yalamanda Varla, Vishvesh Joshi, Rikin Patel, and Derajram Benival3.1 Introduction 813.2 Techniques for Nanosizing 873.3 Formulation Strategies for Nanosized Drugs 933.4 Challenges and Limitations in Nanosizing 963.5 Future Perspectives 983.6 Conclusion 994 Pharmaceutical Cocrystals 115Ghaida Mustafa, Shahzeb Khan, and Anant Paradkar4.1 Introduction 1154.2 Synthon Theory and Prediction Tools in Cocrystal Design 1194.3 Synthesis of Pharmaceutical Cocrystals 1244.4 Characterization Techniques of Pharmaceutical Cocrystals 1324.5 Solubility Aspects of Pharmaceutical Cocrystals 1394.6 Pharmaceutical Cocrystals: Physicochemical Properties and Applications 1414.7 Regulatory Considerations and Approval Pathways 1514.8 Commercially Available Cocrystals-Based Pharmaceuticals 1534.9 Challenges and Future Perspectives 1534.10 Conclusion 1565 Self-Microemulsifying and Self-Emulsifying Drug Delivery Systems to Improve Solubility and Bioavailability 173Dipak B. Bari, Rakhee Kapadia, Raju O. Sonawane, Kamalesh D. Mali, Vivek P. Rajkule, Mahesh G. Umbarkar, and Chandrakantsing V. Pardeshi5.1 Introduction 1735.2 Self-Emulsifying Drug Delivery Systems 1745.3 Advantages and Disadvantages of SEDDS/SMEDDS 1755.4 Formulation of SEDDS and SMEDDS 1755.5 Challenges in Formulation Development of SEDDS/SMEDDS 1825.6 Mechanism of Self-Emulsification 1875.7 Self-Emulsification and Uptake of Drugs In Vivo 1875.8 Applications of SEDDS 1885.9 Regulatory Updates on SMEDDS/SNEDDS 1945.10 Commercial SEDDS 1945.11 Patents on SEDDS 1955.12 Clinical Status of SEDDS Formulations 1955.13 Conclusion 1956 Liposomes and Mixed Micelles for Improvement of Drug Solubility 209Chukwuebuka E. Umeyor, Diksha Narula, Ankita Anure, Andrew Ezegbe, Prafull Kolekar, and Vandana B. Patravale6.1 Introduction 2096.2 Drug Carrier Solubility Enhances Drug Bioavailability 2106.3 Process Development of Liposomes 2116.4 Mixed Micelles for Enhanced Drug Solubility 2286.5 In vivo Safety of Liposomes and Mixed Micelles Drug Carriers 2336.6 Benefits and Limitations of Liposomes and Mixed Micelles 2346.7 Marketed Micellar and Liposomal Products 2376.8 Regulatory Guidelines for Liposomes and Mixed Micelles Use 2376.9 Clinical Application of Liposomes and Mixed Micelles 2416.10 Patent Landscape of Liposomes and Mixed Micelles 2446.11 Future Research and Conclusion 2447 Improvement of Solubility and Bioavailability of Poorly Soluble Drugs Using Mesoporous Silica Particles 257Jitendra Wankar and Sonia Gera7.1 Introduction 2577.2 Different Techniques for Synthesis of Silica Particles 2587.3 Characterization of MSN 2607.4 Mesoporous Silica for Drug Dissolution and Dosage Form Development 2617.5 Drug-Loading Methods in Mesoporous Silica Particles to Improve Drug Solubility 2627.6 Mesoporous Silica Particles as a Potential Option to Improve Bioavailability (BA) 2677.7 Commercial Success and Clinical Pipeline Using This Technology 2697.8 Challenges Toward Clinical Translation of Mesoporous Silica Particles 2707.9 Future Prospects and Conclusions 2718 Gastrointestinal Dissolution and Absorption of BCS Class II Drugs 277Almog Eliyahu Dahan and Arik Dahan8.1 Introduction 2778.2 Drug Absorption and the BCS 2778.3 GI Physiological Variables Affecting BCS Class II Drug Dissolution 2808.4 In vitro Dissolution Tests for Class II Drugs 2848.5 Biowaiver Extension Potential 2858.6 Advanced Simulation Models for FDA Biowaiver Submission 2868.7 Conclusions 2889 Cyclodextrin-Based Formulations to Improve Solubility of Poorly Soluble Drugs 297Ganesh Shevalkar, Shradhha Tiwari, Deepak Bari, Chandrakantsing Pardeshi, and Sarika Kamble9.1 Introduction 2979.2 CD Structure and Types 2989.3 Approved CD-Based Pharmaceutical Formulations 3049.4 Drug Delivery Applications of CD-Based Formulations 3069.5 Current Landscape Post Approval of Captisol 3119.6 Regulatory and Clinical Landscape of Cyclodextrin-Based Biomaterials 3129.7 Toxicological Considerations of CDs with Emphasis on Renal Safety 3149.8 Patent Scenario Regarding the Use of CD 3169.9 Conclusion 31810 Cosolvent-Based Formulations to Improve Solubility and Bioavailability 327Nilam Bhusare, Chetana Eknure, Yogeshwar Bachhav, and Maushmi S. Kumar10.1 Background of the Cosolvent-Based Formulations 32710.2 Cosolvency 32810.3 Types of Cosolvents Allowed and Their IIG Limits 33410.4 Possible Adverse Events Due to the Use of Cosolvents—Case Studies 33610.5 Challenges in Selecting a Formulation in the Preclinical Studies Using Cosolvents 33710.6 Design of Formulations Using Cosolvents for First-in-Man Studies or Late Clinical Phases 33910.7 Regulatory Aspects 33910.8 Selected Examples of Cosolvent-Based Formulations Using 505(b)(2) Pathway and Intellectual Property (IP) Protection 34010.9 Clinical Pipeline 34410.10 Future Prospects 34510.11 Conclusion 34511 First-in-Animal Studies and Formulation Considerations 353Dnyaneshwar N. Kapote and Vandana Gawande-Kapote11.1 Introduction 35311.2 Steps in Preclinical Studies 35511.3 Pre-Formulation Considerations for First-in-Animal Studies (Preclinical Formulations) 35611.4 Formulation Considerations for First-in-Animal Formulations 36311.5 Bridging the Gap of First-in-Animal Studies with First-in-Human Studies 37711.6 Conclusions 37812 Improving Aqueous Solubility of Drug Candidates Through Structural Modifications 389Kamal Kumar12.1 Introduction 38912.2 Enhancing Drug Solubility and Bioavailability: A Key to Effective Therapy 39112.3 Chemical Modification as a Strategy to Enhance Solubility 39412.4 Conclusion 410References 411Index 419