The 2019 AAPS Distinguished Pharmaceutical Scientist Award winner, Samuel Yalkowsky, has contributed greatly to the advancement of science while mentoring early careerists.
By Mark Crawford
Samuel Yalkowsky, Ph.D., is professor of pharmaceutics at the College of Pharmacy, University of Arizona, Tucson. His long and distinguished career as a pharmaceutical scientist includes 13 years in the pharmaceutical industry (1969–1982) and 37 years in academia at the University of Arizona (1982–present). In honor of his many achievements over five decades of pharmaceutical research, AAPS presented Yalkowsky with the Distinguished Pharmaceutical Scientist Award in 2019.
As a research scientist at The Upjohn Company, he participated in the formulation of a number of oral and parenteral products including Halcion tablets and Xanax tablets. During his tenure in the pharmaceutical industry, Yalkowsky published approx. 50 peer-reviewed research papers, two of which received the prestigious Ebert Prize from the American Pharmaceutical Association for best contributions to the Journal of Pharmaceutical Sciences. “This is truly a rare achievement for a scientist working in an industrial setting,” notes friend and colleague Abu Serajuddin, professor of industrial pharmacy at the College of Pharmacy and Health Sciences at St. John’s University.
Yalkowsky is perhaps best known for his groundbreaking work in organic compound solubility and his solubilization strategies for dosage form design. His research focuses on relationships between chemical structure and physical phenomena, such as solubility, partitioning, and melting. “His work in predicting octanol-water partition coefficients to water and co-solvent solubility represented the first significant expansion of the thermodynamic theory of solubilization in many years,” says Ken Morris, professor of pharmaceutics and director of the Lachman Institute for Pharmaceutical Analysis at Long Island University. “This completely changed the way pharmaceutical scientists evaluate the developability of new active pharmaceutical ingredients.”
Another outstanding contribution to pharmaceutical science is his development of the general solubility equation (GSE), which relates aqueous solubility to partition coefficient and melting point. This state-of-the-art method for calculating aqueous solubility of organic compounds has been successfully applied to literally hundreds, if not thousands, of compounds.
“The GSE is a very simple equation for estimating the solubility of drugs and organic compounds in water,” states Yalkowsky. “The derivation of the equation requires nothing more than arithmetic and is based on two well-known concepts—Walden’s rule and the definition of the octanol-water partition coefficient. This equation is now given in textbooks and is frequently cited. The fact that I am not good with math makes it very satisfying to have generated such a useful equation.”
Yalkowsky has published 280 peer-reviewed journal articles and eight books over his career, including the essential Solubility and Solubilization in Aqueous Media, which outlines his methods for predicting and modifying aqueous solubility without altering the drug structure. He also owns five patents.
Perhaps lesser known is the impact of his solubility work on the environmental sciences, especially regarding pollutant solubility and organic solute movement in groundwater. His solubility models were the basis for one of the most influential and cited U.S. Environmental Protection Agency papers on the accumulation of hydrophobic pollutants in lake and stream systems. “This work was seminal in groundwater modeling of the fate and distribution of very dangerous compounds in the U.S. and worldwide,” adds Morris. “The result was that the entire environmental community became aware of the contributions from pharmaceutics to a much broader area of impactful research.”
Teacher, Mentor, Friend
As a dedicated and enthusiastic teacher, Yalkowsky has maintained a very active graduate research program and has worked with more than 50 graduate students and postdocs. Many of his former students now have key roles in the pharmaceutical industry and academia. Yalkowsky was awarded the University of Arizona Graduate Teaching and Mentoring Award, a university-wide award initiated by graduate students.
“I hired four of Sam’s Ph.D. graduates from his laboratory as senior scientists for Bristol-Myers Squibb and Novartis,” says Serajuddin. “Because of the strength of training in his laboratory, all of them contributed greatly to the successes of these companies.”
Yalkowsky’s philosophy of teaching goes back to professor George Zografi at the University of Michigan, “who encouraged me to follow my intuition, allowed me to change my research project, and encouraged me in my new research direction,” says Yalkowsky. “One of the most important characteristics that makes a person successful in the pharmaceutical industry or academia is the willingness to trust one’s intuition and to take a chance.” He continues to follow this approach in his own research and passes it on to his students.
“Many students enter graduate school with the belief that there is one answer to every problem, and that it can be found in the textbook,” he notes. “One of the first things a professor must do is to help the student unlearn much of what they acquired in undergraduate school. Students must be shown how to utilize the knowledge that they acquired in their coursework in a variety of new ways, and they must learn how to create new knowledge. Graduate education must be broad based with emphasis upon the fundamental principles of pharmaceutics, rather than on the latest scientific trend.”
Yalkowsky spends a great deal of time assisting students with the design of their research experiments and in the analysis of their data. He stresses the use of lateral or creative thinking and encourages students to not be afraid of trying new approaches. “Students must be encouraged to try new approaches to problems, even though they are not sure that the approaches will work,” he says. “An experiment that did not work is not a failure if we learn something from it. Often an apparently unsuccessful experiment will lead to the design of a successful one.”
Morris observes that Yalkowsky and his graduate students and postdoctoral fellows are a “fixture” at annual AAPS meetings, with multiple contributions virtually every year, as well as contributions to the AAPS journals. “A few of his mentees are in academia, but the majority have chosen industrial careers and have helped industry make the transition to science-based drug development, as demanded both by the challenges of complex molecules and the associated regulatory requirements,” says Morris.
Achievements to Come
Yalkowsky continues to stay active as researcher and educator. He joined the Academy of Pharmaceutical Sciences (APS) after he graduated from pharmacy school and has been a member since 1965. Since AAPS branched off from APS in 1986, he has attended nearly every AAPS meeting, served in various AAPS leadership roles, and contributed to more than 40 symposia, conferences, and short courses. “AAPS has enabled me to meet and interact with my colleagues and develop very meaningful professional relationships, as well as lifelong friendships,” he says.
Yalkowsky is intently focused on developing a book on UPPER (unified physicochemical property estimation relationships), which relates many compound properties to chemical structure. “Because it enables the calculation of the physicochemical properties that are most important in the pharmaceutical and biological sciences, I hope to use UPPER to top off my career,” he states.
“Sam has spent much of his career researching UPPER and his efforts continue to this day,” says Michael Mayersohn, professor emeritus of pharmaceutical sciences at University of Arizona’s College of Pharmacy. “Fundamentally, he has established a network that allows going from one thermodynamic parameter to another by virtue of simplified relationships that he and his group have developed over the years. This approach has already proven useful—I expect that its impact in the field will become more obvious and its use will come into common practice as additional publications evaluate its utility.”
Mark Crawford is a science and technology freelance writer based in New Mexico.