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Studying the effect of solubilizing agents on drug diffusion through the unstirred water layer (UWL) by localized spectroscopy

Permanent lenke
https://hdl.handle.net/10037/17183
DOI
https://doi.org/10.1016/j.ejpb.2019.04.005
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article.pdf (1.071Mb)
Akseptert manusversjon (PDF)
Dato
2019-04-04
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Di Cagno, Massimiliano Pio; Stein, Paul C
Sammendrag
An experimental/computational approach has been successfully applied in order to study the effect of solubilizing vehicles (cyclodextrins and liposomes) on the passive diffusion of four active pharmaceutical ingredients (API) of different nature (hydrophilic, ionizable and lipophilic) through an unstirred water layer (UWL) model. This approach allowed the measurement of flux changes through the UWL and the computational calculation of different parameters relevant to interpret the interplay within solubilizing vehicles and UWL diffusion. In the case of cyclodextrin, this approach allowed the determination of free drug diffusivity (Df), bound drug diffusivity (Db) and the equilibrium constant (K). In the case of liposomes, the experimental approach allowed the determination of the liposomes/water partition coefficient (Plip/w) as well as relative API diffusivity ((D), i.e. the drug diffusion in the presence of solubilizing agents). This work demonstrates that the presence of solubilizing vehicles hampers the diffusion of API through UWL due to a combination of reduction in relative diffusivity and concentration gradient. These results are highly relevant as they might help to explain why biological performance of API is affected by the presence of solubilizing/complexing agents.
Beskrivelse
Accepted manuscript version, licensed CC BY-NC-ND 4.0.
Forlag
Elsevier
Sitering
Di Cagno MP, Stein PC. Studying the effect of solubilizing agents on drug diffusion through the unstirred water layer (UWL) by localized spectroscopy. European journal of pharmaceutics and biopharmaceutics. 2019;139:205-212
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© 2019 Elsevier B.V. All rights reserved.

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