Arik Dahan
Ben-Gurion University of the Negev, Israel
Title: The solubility-permeability interplay in Formulation Development for Low-Solubility Drugs
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, what are the effects on the apparent permeability? 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, our results on this solubility-permeability interplay will be presented. Decreased apparent permeability accompanied the solubility increase when different solubilisation methods are employed; however, increasing the apparent solubility by super saturation e.g. via amorphous solid dispersions, circumvented the solubility-permeability trade-off, and the permeability remained steady. Most recently, even increased permeability was discovered, when the super saturation saturated efflux processes. Overall, the solubility-permeability interplay cannot be ignored when using solubility-enabling formulations; looking solely at the solubility may be misleading with regards to absorption predictions, 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.