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Updated: Jul 7, 2025

Self-Nanoemulsification of Healthy Oils to Enhance the Solubility of Lipophilic Drugs
Published on: July 27, 2022
Solubility-enabling formulations for oral delivery of lipophilic drugs: considering the solubility-permeability
1Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Introduction:
Tackling low water solubility of drug candidates is a major challenge in today's pharmaceutics/biopharmaceutics, especially by means of modern solubility-enabling formulations. However, drug absorption from these formulations oftentimes remains unchanged or even decreases, despite substantial solubility enhancement.
Areas Covered:
In this article, we overview the simultaneous effects of the formulation on the solubility and the apparent permeability of the drug, and analyze the contribution of this solubility-permeability interplay to the success/failure of the formulation to increase the overall absorption and bioavailability. Three different patterns of interplay were identified: (1) solubility-permeability tradeoff in which every solubility gain comes with a price of concomitant permeability loss; (2) an advantageous interplay pattern in which the permeability remains unchanged alongside the solubility gain; and (3) an optimal interplay pattern in which the formulation increases both the solubility and the permeability. Passive vs. active intestinal permeability considerations in the context of the solubility-permeability interplay are also thoroughly discussed.
Expert Opinion:
The solubility-permeability interplay pattern of a given formulation has a critical effect on its overall success/failure, and hence, taking into account both parameters in solubility-enabling formulation development is prudent and highly recommended.
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