Oral delivery of lipophilic drugs: The solubility-permeability interplay and formulation design

Title : Oral delivery of lipophilic drugs: The solubility-permeability interplay and formulation design

Abstract:

Poor aqueous solubility is a major challenge in today’s biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect on the drug’s apparent permeability has been largely overlooked. The mathematical equation to describe the membrane permeability of a drug comprises the membrane/aqueous partition coefficient, which in turn is dependent on the drug’s apparent solubility in the GI milieu, suggesting that the solubility and the permeability are closely related, exhibit a certain interplay between them, and treating the one irrespectively of the other may be insufficient. In this lecture, an overview of this solubility-permeability interplay will be provided, and the available data will be analyzed in the context of the effort to maximize the overall drug exposure. Overall, depending on the type of solubility-permeability interplay, the permeability may decrease, remain unchanged, and even increase, in a way that may critically affect the formulation capability to improve the overall absorption. Therefore, an intelligent design of solubility-enabling formulation needs to consider both the solubility afforded by the formulation and the permeability in the new luminal environment resulting from the formulation.

Takeaway Notes: Overall, depending on the type of solubility-permeability interplay, the permeability may decrease, remain unchanged, and even increase, in a way that may critically affect the formulation capability to improve the overall absorption; the audience will learn that intelligent design of solubility-enabling formulation needs to consider both the solubility afforded by the formulation and the permeability in the new luminal environment resulting from the formulation. The audience will be able to implement these principles to develop better oral formulations for lipophilic drug candidates.

Biography:

Arik Dahan is an Associate Professor of Pharmaceutics and Biopharmaceutics at the Department of Clinical Pharmacology and the School of Pharmacy, Ben-Gurion University of the Negev in Beer-Sheva, Israel. He is also an Adjunct Professor of Pharmaceutical Sciences at the College of Pharmacy, University of Michigan, USA. Dr Dahan received his Ph.D. (2007) from the Hebrew University of Jerusalem. From 2007 until 2009 he was a Post-Doctoral Research Fellow at the University of Michigan College of Pharmacy with Professor Gordon Amidon. Dr Dahan’s research interest is the integration of up-to-date molecular and cellular mechanistic investigations of drug disposition in the context of the human body, in order to enable successful drug delivery and therapy. In implementing this molecular biopharmaceutical approach to ADME research, Dr Dahan is seeking to enable mechanistic-based successful solutions to drug delivery, especially (but not only) oral, in challenging scenarios e.g. low-solubility, low-permeability, efflux transport, extensive metabolism, poor site targeting, various pathophysiological conditions (e.g. obesity, inflammatory bowel disease), and pediatrics patient care. He has authored over 70 top-notch Journal papers, and contributed chapters to 7 books.