Fasted and fed state human duodenal fluids: Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability

Research output: Contribution to journalJournal articlepeer-review

Standard

Fasted and fed state human duodenal fluids : Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability. / Dahlgren, D.; Venczel, M.; Ridoux, J. P.; Skjöld, C.; Müllertz, A.; Holm, R.; Augustijns, P.; Hellström, P. M.; Lennernäs, H.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 163, 2021, p. 240-251.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Dahlgren, D, Venczel, M, Ridoux, JP, Skjöld, C, Müllertz, A, Holm, R, Augustijns, P, Hellström, PM & Lennernäs, H 2021, 'Fasted and fed state human duodenal fluids: Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability', European Journal of Pharmaceutics and Biopharmaceutics, vol. 163, pp. 240-251. https://doi.org/10.1016/j.ejpb.2021.04.005

APA

Dahlgren, D., Venczel, M., Ridoux, J. P., Skjöld, C., Müllertz, A., Holm, R., Augustijns, P., Hellström, P. M., & Lennernäs, H. (2021). Fasted and fed state human duodenal fluids: Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability. European Journal of Pharmaceutics and Biopharmaceutics, 163, 240-251. https://doi.org/10.1016/j.ejpb.2021.04.005

Vancouver

Dahlgren D, Venczel M, Ridoux JP, Skjöld C, Müllertz A, Holm R et al. Fasted and fed state human duodenal fluids: Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability. European Journal of Pharmaceutics and Biopharmaceutics. 2021;163:240-251. https://doi.org/10.1016/j.ejpb.2021.04.005

Author

Dahlgren, D. ; Venczel, M. ; Ridoux, J. P. ; Skjöld, C. ; Müllertz, A. ; Holm, R. ; Augustijns, P. ; Hellström, P. M. ; Lennernäs, H. / Fasted and fed state human duodenal fluids : Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability. In: European Journal of Pharmaceutics and Biopharmaceutics. 2021 ; Vol. 163. pp. 240-251.

Bibtex

@article{a082ddc0159c447db14a6a08cbdf1df0,
title = "Fasted and fed state human duodenal fluids: Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability",
abstract = "Accurate in vivo predictions of intestinal absorption of low solubility drugs require knowing their solubility in physiologically relevant dissolution media. Aspirated human intestinal fluids (HIF) are the gold standard, followed by simulated intestinal HIF in the fasted and fed state (FaSSIF/FeSSIF). However, current HIF characterization data vary, and there is also some controversy regarding the accuracy of FaSSIF and FeSSIF for predicting drug solubility in HIF. This study aimed at characterizing fasted and fed state duodenal HIF from 16 human volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well as protein, phospholipid, and bile salt content. The fasted and fed state HIF samples were further used to investigate the equilibrium solubility of 17 representative low-solubility small-molecule drugs, six of which were confidential industry compounds and 11 were known and characterized regarding chemical diversity. These solubility values were then compared to reported solubility values in fasted and fed state HIF, FaSSIF and FeSSIF, as well as with their human bioavailability for both states. The HIF compositions corresponded well to previously reported values and current FaSSIF and FeSSIF compositions. The drug solubility values in HIF (both fasted and fed states) were also well in line with reported solubility data for HIF, as well as simulated FaSSIF and FeSSIF. This indicates that the in vivo conditions in the proximal small intestine are well represented by simulated intestinal fluids in both composition and drug equilibrium solubility. However, increased drug solubility in the fed vs. fasted states in HIF did not correlate with the human bioavailability changes of the same drugs following oral administration in either state.",
keywords = "Bioavailability, Drug absorption, Drug delivery, Drug dissolution, Drug solubility, Food effects, Human intestinal fluids",
author = "D. Dahlgren and M. Venczel and Ridoux, {J. P.} and C. Skj{\"o}ld and A. M{\"u}llertz and R. Holm and P. Augustijns and Hellstr{\"o}m, {P. M.} and H. Lennern{\"a}s",
note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
doi = "10.1016/j.ejpb.2021.04.005",
language = "English",
volume = "163",
pages = "240--251",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Fasted and fed state human duodenal fluids

T2 - Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability

AU - Dahlgren, D.

AU - Venczel, M.

AU - Ridoux, J. P.

AU - Skjöld, C.

AU - Müllertz, A.

AU - Holm, R.

AU - Augustijns, P.

AU - Hellström, P. M.

AU - Lennernäs, H.

N1 - Publisher Copyright: © 2021 The Author(s)

PY - 2021

Y1 - 2021

N2 - Accurate in vivo predictions of intestinal absorption of low solubility drugs require knowing their solubility in physiologically relevant dissolution media. Aspirated human intestinal fluids (HIF) are the gold standard, followed by simulated intestinal HIF in the fasted and fed state (FaSSIF/FeSSIF). However, current HIF characterization data vary, and there is also some controversy regarding the accuracy of FaSSIF and FeSSIF for predicting drug solubility in HIF. This study aimed at characterizing fasted and fed state duodenal HIF from 16 human volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well as protein, phospholipid, and bile salt content. The fasted and fed state HIF samples were further used to investigate the equilibrium solubility of 17 representative low-solubility small-molecule drugs, six of which were confidential industry compounds and 11 were known and characterized regarding chemical diversity. These solubility values were then compared to reported solubility values in fasted and fed state HIF, FaSSIF and FeSSIF, as well as with their human bioavailability for both states. The HIF compositions corresponded well to previously reported values and current FaSSIF and FeSSIF compositions. The drug solubility values in HIF (both fasted and fed states) were also well in line with reported solubility data for HIF, as well as simulated FaSSIF and FeSSIF. This indicates that the in vivo conditions in the proximal small intestine are well represented by simulated intestinal fluids in both composition and drug equilibrium solubility. However, increased drug solubility in the fed vs. fasted states in HIF did not correlate with the human bioavailability changes of the same drugs following oral administration in either state.

AB - Accurate in vivo predictions of intestinal absorption of low solubility drugs require knowing their solubility in physiologically relevant dissolution media. Aspirated human intestinal fluids (HIF) are the gold standard, followed by simulated intestinal HIF in the fasted and fed state (FaSSIF/FeSSIF). However, current HIF characterization data vary, and there is also some controversy regarding the accuracy of FaSSIF and FeSSIF for predicting drug solubility in HIF. This study aimed at characterizing fasted and fed state duodenal HIF from 16 human volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well as protein, phospholipid, and bile salt content. The fasted and fed state HIF samples were further used to investigate the equilibrium solubility of 17 representative low-solubility small-molecule drugs, six of which were confidential industry compounds and 11 were known and characterized regarding chemical diversity. These solubility values were then compared to reported solubility values in fasted and fed state HIF, FaSSIF and FeSSIF, as well as with their human bioavailability for both states. The HIF compositions corresponded well to previously reported values and current FaSSIF and FeSSIF compositions. The drug solubility values in HIF (both fasted and fed states) were also well in line with reported solubility data for HIF, as well as simulated FaSSIF and FeSSIF. This indicates that the in vivo conditions in the proximal small intestine are well represented by simulated intestinal fluids in both composition and drug equilibrium solubility. However, increased drug solubility in the fed vs. fasted states in HIF did not correlate with the human bioavailability changes of the same drugs following oral administration in either state.

KW - Bioavailability

KW - Drug absorption

KW - Drug delivery

KW - Drug dissolution

KW - Drug solubility

KW - Food effects

KW - Human intestinal fluids

U2 - 10.1016/j.ejpb.2021.04.005

DO - 10.1016/j.ejpb.2021.04.005

M3 - Journal article

C2 - 33872761

AN - SCOPUS:85104670017

VL - 163

SP - 240

EP - 251

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -

ID: 279127297