Comparison of lipophilic and size-exclusion membranes: the effect of stirring and cyclodextrin in the donor compartment: Original scientific article

Petra Tozser; Szabina Kádár; Edina Szabó; Máté Dobó; Gergo Toth; György Tibor Balogh; Peter Soti; Bálint Sinkó; Eniko Borbas

doi:10.5599/admet.2753

Authors

Petra Tozser Budapest University of Technology and Economics, Hungary https://orcid.org/0009-0007-4725-8884
Szabina Kádár Budapest University of Technology and Economics, Hungary https://orcid.org/0000-0002-7818-2145
Edina Szabó Budapest University of Technology and Economics, Hungary https://orcid.org/0000-0001-9616-5122
Máté Dobó Semmelweis University, Hungary https://orcid.org/0000-0003-2573-445X
Gergo Toth Semmelweis University, Hungary https://orcid.org/0000-0001-5341-319X
György Tibor Balogh Semmelweis University, Hungary https://orcid.org/0000-0001-8273-1760
Peter Soti Lavet Pharmaceutical Ltd., Hungary https://orcid.org/0009-0006-6765-9047
Bálint Sinkó Pion Inc, Hungary https://orcid.org/0009-0005-8256-4348
Eniko Borbas Budapest University of Technology and Economics, Hungary https://orcid.org/0000-0002-9393-9978

DOI:

https://doi.org/10.5599/admet.2753

Keywords:

unstirred water layer, membrane transport, solubility, supersaturation ratio, carvedilol

Abstract

Background and purpose: The effective transport of an active pharmaceutical ingredient across various membrane systems is critical for enhancing its bioavailability, especially in formulations involving solubilizing agents. This study aims to investigate the permeability differences of carvedilol (CAR) between lipophilic and size-exclusion membranes in the presence of hydroxypropyl-beta-cyclodextrin (HP-β-CD) using in vitro side-by-side diffusion cell assays. Experimental approach: Solubility and permeability assays confirmed that HP-β-CD significantly enhanced the solubility of CAR, while simultaneously decreasing its permeability, indicating an interplay between the two parameters. Key results: A mathematical model based on Fick’s first law of diffusion was developed to describe drug transport across the UWL, and generally through the UWL-membrane system, with a particular focus on the role of solubilizing agents. Conclusion: Results from both the UWL and membrane limited transport conditions demonstrated that the supersaturation ratio (SSR, defined as the ratio of the drug concentration present in solution to its thermodynamic solubility measured in exactly the same media) between donor and acceptor compartments is the real driving force of the transport, when the complexing agent and the drug- HP-β-CD complex does not penetrate the membrane or the permeation of the solubilizing additive through the membrane is relatively slow, so it does not affect the transport of the API substantially.

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