Evaluating side-by-side diffusion models for studying drug supersaturation in an absorptive environment: a case example of fenofibrate and felodipine
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Evaluating side-by-side diffusion models for studying drug supersaturation in an absorptive environment: a case example of fenofibrate and felodipine. / Eliasen, Jannik Nicklas; Berthelsen, Ragna; Slot, Anne Louise; Mullertz, Anette.
In: Journal of Pharmacy and Pharmacology, Vol. 72, No. 3, 2020, p. 371-384.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Evaluating side-by-side diffusion models for studying drug supersaturation in an absorptive environment: a case example of fenofibrate and felodipine
AU - Eliasen, Jannik Nicklas
AU - Berthelsen, Ragna
AU - Slot, Anne Louise
AU - Mullertz, Anette
PY - 2020
Y1 - 2020
N2 - ObjectiveTo test whether a side-by-side diffusion model is suitable for studying drug supersaturation in an absorptive environment.MethodsThe µD/P model and the µFLUX model, using a Caco-2 cell monolayer/PAMPA membrane as the permeation barrier, respectively, were compared in terms of robustness and ease of handling, while studying the drug supersaturation–precipitation–permeation interplay. Continuing with the best model, the impact of the acceptor media and the importance of studying drug supersaturation in a combined dissolution–permeation model, as compared to a simple dissolution model, were evaluated.Key findingsThe two models produced similar results in terms of supersaturation, precipitation and permeation. The µFLUX model was considered more robust and easier to handle based on its cell-free permeation system. Using the µFLUX model, it was found that an acceptor medium with a high surfactant concentration increased the amount of permeated drug. The effect of absorption on drug supersaturation was found to be dependent on the drug, and the tested level of supersaturation.ConclusionThe tested models were comparable; however, Caco-2 cell monolayers were considered too sensitive to be used to study drug supersaturation. Further studies are needed to evaluate the observed drug-dependent effects of absorption on drug supersaturation.
AB - ObjectiveTo test whether a side-by-side diffusion model is suitable for studying drug supersaturation in an absorptive environment.MethodsThe µD/P model and the µFLUX model, using a Caco-2 cell monolayer/PAMPA membrane as the permeation barrier, respectively, were compared in terms of robustness and ease of handling, while studying the drug supersaturation–precipitation–permeation interplay. Continuing with the best model, the impact of the acceptor media and the importance of studying drug supersaturation in a combined dissolution–permeation model, as compared to a simple dissolution model, were evaluated.Key findingsThe two models produced similar results in terms of supersaturation, precipitation and permeation. The µFLUX model was considered more robust and easier to handle based on its cell-free permeation system. Using the µFLUX model, it was found that an acceptor medium with a high surfactant concentration increased the amount of permeated drug. The effect of absorption on drug supersaturation was found to be dependent on the drug, and the tested level of supersaturation.ConclusionThe tested models were comparable; however, Caco-2 cell monolayers were considered too sensitive to be used to study drug supersaturation. Further studies are needed to evaluate the observed drug-dependent effects of absorption on drug supersaturation.
KW - In-vitro model design
KW - permeation
KW - precipitation
KW - side-by-side diffusion model
KW - supersaturation
U2 - 10.1111/jphp.13218
DO - 10.1111/jphp.13218
M3 - Journal article
C2 - 31876955
VL - 72
SP - 371
EP - 384
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 3
ER -
ID: 239857501