This is a comprehensive textbook addressing the unique aspects of drug development for ophthalmic use. Beginning with a perspective on anatomy and physiology of the eye, the book provides a critical appraisal of principles that underlie ocular drug product development. The coverage encompasses topical and intraocular formulations, small molecules and biologics (including protein and gene therapies), conventional formulations (including solutions, suspensions, and emulsions), novel formulations (including nanoparticles, microparticles, and hydrogels), devices, and specialty products. Critical elements such as pharmacokinetics, influence of formulation technologies and ingredients, as well as impact of disease conditions on products development are addressed. Products intended for both the front and the back of the eye are discussed with an eye towards future advances.

Autorentext

Seshadri Neervannan, Ph.D., Chief Operating Officer, Tarsus Pharmaceuticals Inc. is a distinguished thought leader and an expert in global drug development. His expertise spans a broad range of novel therapeutic agents beginning from their discovery through commercialization. He is focused on innovation, processes, and strategies, and he has a demonstrated record of securing multiple global product approvals in eye care and other therapeutic areas. Spanning over two decades in R&D, leading various product development functions, he has developed many drug products including topical ophthalmic preparations, intraocular sustained release injectables, dermal products, drug-device combination products, oral dosage forms and parenteral injectables for small molecules and biologics. He received his Ph.D. in Pharmaceutical Chemistry from the University of Kansas.








Uday B. Kompella, Ph.D., Professor of Pharmaceutical Sciences, Ophthalmology, and Bioengineering and Co-director of the Colorado Center for Nanomedicine and Nanosafety the University of Colorado, is an expert in ocular drug delivery and development. He is a Co-founder of Ocugen, Inc., a public company focused on developing novel biologics for treating eye diseases. Dr. Kompella is a Fellow of the American Association of Pharmaceutical Scientists and the Association for Research in Vision and Ophthalmology. Dr. Kompella is a recipient of the Distinguished Scientist Award and Distinguished Teacher Award at the University of Nebraska Medical Center; Dean's Mentoring Award and Innovations in Science Award at University of Colorado Anschutz Medical Campus; and Undergraduate Alumni Teaching Excellence Award at Auburn University. He is also a recipient of the ARVO Foundation for Eye Research/Pfizer Ophthalmics/Carl Camras Translational Research Award in Ophthalmology. Dr. Kompella has extensive experience as an editor of scientific journals, including Expert Opinion on Drug Delivery (Editor-in-Chief, 10 years), Pharmaceutical Research (Editor, 16 years), Journal of Ocular Pharmacology and Therapeutics (Associate Editor, 10 years), and Clinical Research and Regulatory Affairs (Editor, 4 years). Dr. Kompella obtained his Ph.D. in Pharmaceutical Sciences from the University of Southern California.

Inhalt

Preface

Section A. Introduction and background

1. Introduction and History of Ophthalmic Product Development

Sesha Neervannan

2. Ocular Surface Anatomy and Physiology: Impact on Product Development

Patrick M. Hughes and Jie Shen

3. Anatomy and Physiology of the Anterior Chamber - Impact on Product Development

SP. Srinivas, Giovanna Guidoboni, Anirudh Burli, Bhavya Harjai, Uday B. Kompella

Section B. Fundamental approach to Ophthalmic Product Development

4. Back of the eye anatomy & physiology - Impact on product development

C G Wilson

5. Physicochemical and Biological Fundamentals for Drug Delivery to the Eye

Imran Ahmed

6. Topical Ophthalmic Dosage Form Development - Key Components and Critical Quality Attributes

Anuradha Gore and Chetan Pujara

7. Intra-ocular Injectable Dosage Form Development

Key Components and Critical Quality Attributes

Kenneth Reed

8. Microbiological Considerations for Ophthalmic Products - Sterility, Endotoxin Limits and Preservatives

Ayako Hasegawa, Melissa Gulmezian-Sefer, Ying Cheng, and Ramakrishnan Srikumar

9. Packaging Development - Multi-dose container closure for preservative free products, extractable/leachables from packaging, new technologies

Michael Regn

Section C. Pharmaceutical Product Development

10. Liquid ophthalmic drug products - physicochemical properties, formulations and manufacturing considerations.

Hovhannes J Gukasyan and Richard Graham

11. Emulsions for topical eye delivery: state of the art and future perspectives

Frederic Lallemand, Jean-Sebastien Garrigue

12. Emulsions for topical eye delivery: state of the art and future perspectives

Frederic Lallemand and Jean-Sebastien Garrigue

13. Microparticle Products For The Eye - preformulation, formulation, and manufacturing considerations

Vanessa Andrés-Guerrero, Irene T. Molina-Martínez,

Irene Bravo-Osuna and Rocío Herrero-Vanrell

14. NANOPARTICLE PRODUCTS FOR THE EYE: preformulation, formulation and manufacturing considerations Sánchez-López E.; Eliana B. Souto; Espina M.; Cano, A.; Ettcheto, M; Camins

15. Advanced Hydrogel Formulations for the Eye

Hu Yang

16. Ophthalmic Product Development for Biologics

Gitanjali Sharma, Chen Zhou, Saurabh Wadhwa, Ashwin C. Parenky, Kenneth S. Graham, Amardeep S. Bhalla, Dingjiang Liu, Hunter H. Chen, Mohammed Shameem

Section D. Specialty Products and Generic Development

17. Implantable Devices to Treat Ophthalmic Conditions -Drug Delivery Systems

Susan Lee, Laszlo Romoda, Michael Robinson

18. Development of Artificial Tears Products for Ocular Conditions

Peter Simmons

19. Approval of Topical Ophthalmic Generic Products in the US - Simple to Complex Dosage Forms and Establishing Equivalency

Stephanie H. Choi, Yan Wang, and Darby Kozak

20. The development and commercialization of sustained-release ocular drug delivery technologies

Michael J.O'Rourke and Clive G Wilson

21. Manufacturing considerations and challenges for AAV Ocular Gene Therapy

Gerard A. Rodrigues, Evgenyi Shalaev, Thomas K. Karami, James Cunningham, Hongwen M. Rivers, Shaoxin Feng, Dinen Shah and Nigel K. H. Slater

22. Transcorneal Kinetics of Topical Drugs and Nanoparticles

Sangly P. Srinivas, Wanachat Chaiyasan, Anirudh Burli, Giovanna Guidoboni, Riccardo Sacco Abhishek Anand, Amreen H. Siraj, Hemant Kumar Daima, Uday B. Kompella

Section E. Conclusions