Abstract
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.
| Original language | American English |
|---|---|
| Pages (from-to) | 13-29 |
| Number of pages | 17 |
| Journal | Expert Opinion on Drug Delivery |
| Volume | 21 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1 Jan 2024 |
Keywords
- Biopharmaceutics
- drug solubility
- intestinal permeability
- low-solubility compounds
- oral drug absorption
- oral drug delivery
- pharmaceutical formulations
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science