9^th World Drug Delivery Summit

Biography

Biography: Arik Dahan

Abstract

While each of the two key parameters of oral drug absorption, the solubility and the permeability, has been comprehensively studied separately, the relationship and interplay between the two has been largely ignored. For instance, when formulating a low-solubility drug using various solubilization techniques, do we know what is the concomitant effect on the apparent permeability? Permeability is equal to the drug's diffusion coefficient through the membrane times the membrane/aqueous partition coefficient divided by the membrane thickness. The direct correlation between the intestinal permeability and the membrane/aqueous partitioning, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggests that the solubility and the permeability are closely associated, exhibiting certain interplay between them, and the current view of treating the one irrespectively of the other may not be sufficient. In this lecture, I will describe the research have been done thus far, and present new data, to shed light on this solubility-permeability interplay. It has been shown that decreased apparent permeability accompanied the solubility increase when using different solubilization methods. On the other hand, we have recently revealed that when increasing the apparent solubility by supersaturation e.g. via amorphous solid dispersions, the solubility-permeability interplay is circumvented, and higher drug flux through the membrane and overall absorption is achieved. Overall, the solubility-permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility enhancement that the formulation enables may be misleading with regards to predicting the resulted absorption, and hence, the solubility-permeability interplay must be taken into account to strike the optimal solubility-permeability balance, in order to maximize the overall absorption.