This program includes an introduction to the problem, the factors governing the oral delivery of drugs, the amorphous state, and processing methods. Then, we will explore the KinetiSol ™ Technology (KSD) with pharmaceutical applications based on published papers. The prevalence of poorly water-soluble drugs is extensive, reported as ~40% of marketed drugs and ~90% of drugs in development. Amorphous solid dispersions (ASD) can overcome two of the three critical variables affecting oral drug delivery, solubility limited process and dissolution limited process. Hot-melt extrusion (HME) and spray-drying (SD) are two often used methods to make ASDs, but HME has limitations that require the drug to be thermally stable, have a melting point <~200oC and the drug/polymer composition have low viscosity, and SD has limitations related to drug solubility in an organic solvent (at least 10-20% w/w. Therefore, more manufacturing options are required in the design space for poorly water-soluble drugs. Such an alternative is KSD, which is a high energy, fusion-based technique that produces ASDs by mechanical mixing at a rate this is > HME. Though KinetiSol® is a fusion-based technique like hot melt extrusion, it differs from hot melt extrusion because thermal energy is not input into the system. Instead, heat is generated by friction and shear imparted on the drug-excipient(s) mixture. Molten product is instantly ejected from the KSD chamber once a set-point temperature is achieved, which is often well below the melting point of the drug. KSD has been successfully applied to compositions that were unable to be processed by hot melt extrusion, including those containing thermally sensitive drugs, like ritonavir, high melting point drugs, like meloxicam (at 270oC ) and hydrocortisone (at 220oC ), and high viscosity polymers, like polyvinyl alcohol. Likewise, KSD has also been used successfully for drugs that are unable to be spray-dried due to insufficient solubility in organic solvents, like fenbendazole. In summary, the manufacturing and science of the KSD process will be discussed as related to poorly water-soluble drugs.

Learning Objectives:

• At the conclusion of this webinar, participants will understand how ASDs can differ when made by different manufacturing technologies: KinetiSol ™ Technology, hot-melt extrusion, and spray-drying.
• After this webinar, participants will be able to describe the KinetiSol ™ Technology manufacturing and scale-up considerations for an amorphous solid dispersion of an insoluble drug.
• At the conclusion of this webinar, participants will understand applications of KinetiSol ™ Technology to improve oral bioavailability of insoluble drugs based on literature examples reviewed in the presentation.

Daniel Davis, PharmD

Daniel Davis received his BS in Chemistry from The University of Texas at Austin in 2015 and PharmD from The University of Texas at Austin College of Pharmacy (UTCOP) in 2019, where he graduated with research honors and academic honors. His research contributions resulted in him receiving the prestigious College of Pharmacy’s Outstanding Research Award. Daniel completed his Ph.D. in 2021 as part of the PharmD/PhD Honor’s program in the Division of Molecular Pharmaceutics and Drug Delivery, and currently works as a Principal Scientist at AustinPX, LLC. Daniel has co-authored over 30 peer-reviewed publications, abstracts, book chapters, and he is a co-inventor on five patent applications. He co-edited the third edition of Formulating Poorly Water-Soluble Drugs (AAPS and Springer) published in 2022. His research is focused on increasing the solubility of poorly water-soluble drugs, specifically focused on innovation formulation designs for increased solubility. Much of this work uses KinetiSol Technology, hot melt extrusion and selective laser sintering three-dimensional printing. Daniel received the B. Berard Matthews Endowed Scholarship, the Van Smith Endowed Presidential Scholarship, and the Undergraduate Research Fellowship from The University of Texas at Austin based on his research. Daniel serves as the Social Media Editor for AAPS PharmSciTech and as a peer-reviewer for other journals including International Journal of Pharmaceutics and AAPS PharmSciTech.

Dave Miller, Ph.D.

Dave A. Miller, Ph.D. is the Chief Scientific Officer at AustinPx. Prior to his current position, Dr. Miller served as Vice President of Research and Development at DisperSol Technologies for over a decade. Before joining DisperSol, he was a Senior Principal Scientist at Hoffmann-La Roche. Dr. Miller specializes in formulation and processing technologies for improving oral bioavailability of insoluble small molecules. He has applied his expertise toward advancing numerous drug candidates through all stages of development from early discovery to line extension. Dr. Miller is an original inventor of the pharmaceutical applications of the KinetiSol technology and continues to be a primary innovative driver for application and expansion of the drug delivery platform. He has co-authored 48 research articles in peer-reviewed journals, co-authored 8 book chapters, and is co-editor of the First, Second, and Third Editions of the textbook, Formulating Poorly Water-Soluble Drugs. He is a co-inventor on 12 granted US patents and numerous granted and pending patents worldwide. Dr. Miller holds a B.S. in Chemical Engineering and a Ph.D. in Pharmaceutics from the University of Texas at Austin.

Robert O. (Bill) Williams III, Ph.D.

Robert O. (Bill) Williams III is the Johnson & Johnson Centennial Chair and Professor of Pharmaceutics and the Division Head of Molecular Pharmaceutics and Drug Delivery at the College of Pharmacy, University of Texas at Austin. He earned a B.S. in Biology from Texas A&M University, a B.S. in Pharmacy from the University of Texas at Austin, and Doctor of Philosophy in Pharmaceutics in 1986 from the University of Texas at Austin. Dr. Williams worked 9 years in the pharmaceutical industry in the United States and France before returning to the University of Texas at Austin in 1995. Dr Williams was elected Fellow of the American Association of Pharmaceutical Scientists in 2006, Fellow of the American Institute of Medical and Biological Engineering in 2008 and Fellow of the National Academy of Inventors in 2019. He was named the Inventor of the Year by the University of Texas at Austin in 2017. He received the College of Science Academy of Distinguished Former Students Award from Texas A&M University in 2021.

Dr. Williams is a member of the American Association of Pharmaceutical Scientists (AAPS), as well as other professional societies including the American Association of Colleges of Pharmacy. He is the co-founder of several pharmaceutical companies. Dr. Williams’ research interests include development of novel drug delivery systems for oral, pulmonary, nasal, injectable, buccal, and topical applications, development of novel particle engineering technologies for low molecular weight drugs, peptides and proteins, and analytical technologies to characterize actives, excipients, and polymers. He has published over 500 peer-reviewed research articles, reviews, abstracts and book chapters, and co-edited several books in the fields of pharmaceutical technology and drug delivery, including Formulating Poorly Water Soluble Drugs, Third Edition (aapspress and Springer). He is an inventor on over 80 patents and patent applications. Dr. Williams served as Editor-in-Chief of the research journal Drug Development and Industrial Pharmacy from 2000 to 2014 and is the Editor-in-Chief of AAPS PharmSciTech (an official publication of AAPS) since 2014. He is on the Editorial Advisory Board of Journal of Drug Delivery Science and Technology and Pharmaceutics, and he serves as a reviewer for numerous other peer-reviewed journals.