Solubility-enabling formulations for oral delivery of lipophilic drugs: considering the solubility-permeability interplay for accelerated formulation development

Noa Fine-Shamir, Arik Dahan

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

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 languageEnglish
Pages (from-to)13-29
Number of pages17
JournalExpert Opinion on Drug Delivery
Volume21
Issue number1
DOIs
StatePublished - 1 Jan 2024

Keywords

  • Biopharmaceutics
  • drug solubility
  • intestinal permeability
  • low-solubility compounds
  • oral drug absorption
  • oral drug delivery
  • pharmaceutical formulations

ASJC Scopus subject areas

  • Pharmaceutical Science

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