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Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats

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Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats. / Christfort, Juliane Fjelrad; Strindberg, Sophie; Plum, Jakob; Hall-Andersen, Jonatan; Janfelt, Christian; Nielsen, Line Hagner; Müllertz, Anette.

I: European Journal of Pharmaceutics and Biopharmaceutics, Bind 142, 2019, s. 307-314.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Christfort, JF, Strindberg, S, Plum, J, Hall-Andersen, J, Janfelt, C, Nielsen, LH & Müllertz, A 2019, 'Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats', European Journal of Pharmaceutics and Biopharmaceutics, bind 142, s. 307-314. https://doi.org/10.1016/j.ejpb.2019.07.007

APA

Christfort, J. F., Strindberg, S., Plum, J., Hall-Andersen, J., Janfelt, C., Nielsen, L. H., & Müllertz, A. (2019). Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats. European Journal of Pharmaceutics and Biopharmaceutics, 142, 307-314. https://doi.org/10.1016/j.ejpb.2019.07.007

Vancouver

Christfort JF, Strindberg S, Plum J, Hall-Andersen J, Janfelt C, Nielsen LH o.a. Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats. European Journal of Pharmaceutics and Biopharmaceutics. 2019;142:307-314. https://doi.org/10.1016/j.ejpb.2019.07.007

Author

Christfort, Juliane Fjelrad ; Strindberg, Sophie ; Plum, Jakob ; Hall-Andersen, Jonatan ; Janfelt, Christian ; Nielsen, Line Hagner ; Müllertz, Anette. / Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats. I: European Journal of Pharmaceutics and Biopharmaceutics. 2019 ; Bind 142. s. 307-314.

Bibtex

@article{680f826606704fc6a816d50c5927a6cb,
title = "Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats",
abstract = "The influence of physiological factors on the solubility of drug compounds has been thoroughly investigated in humans. However, as these factors vary between species and since many in vivo studies are carried out in rats or mice, it has been difficult to establish sufficient in vitro in vivo relations. The aim of this study was to develop a physiologically relevant in vitro dissolution model simulating the gastrointestinal (GI) fluids of fasted rats and compare it to previously published in vitro and in vivo data. To develop the in vitro model, the pH was measured in situ in six segments of the GI tract of anesthetised rats, then the fluids from the stomach, the proximal and the distal small intestine were collected and characterized with regard to osmolality, and bile acid and phospholipid concentration. The pH and osmolality were found to increase throughout the GI tract. The bile acids and phospholipids were present in high concentrations in the proximal small intestine, and the bile acid concentration doubled in the distal part, where the phospholipid concentration decreased. Matrix-assisted laser desorption ionisation mass spectrometry imaging was applied on a cross section of the small intestine, to study which bile acids and phospholipid classes were present in the small intestine of rats. Both cholic acid, taurocholic acid and glycocholic acid were detected, and phosphatidylcholine (34:2) was found to be mainly present in the intestinal wall or mucus, whereas lysophosphatidylcholine (16:0) was also detected in the lumen. Based on these observations, biorelevant media were developed to simulate fluids in the stomach and the proximal part of the small intestine in fasted rats. The media were implemented in a two-step in vitro dissolution model, which was found to better predict the in vivo performance of furosemide, when compared to previously published in vitro and in vivo data.",
keywords = "Biorelevant media, Gastrointestinal fluids, In vitro in vivo correlation, Rats",
author = "Christfort, {Juliane Fjelrad} and Sophie Strindberg and Jakob Plum and Jonatan Hall-Andersen and Christian Janfelt and Nielsen, {Line Hagner} and Anette M{\"u}llertz",
year = "2019",
doi = "10.1016/j.ejpb.2019.07.007",
language = "English",
volume = "142",
pages = "307--314",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Developing a predictive in vitro dissolution model based on gastrointestinal fluid characterisation in rats

AU - Christfort, Juliane Fjelrad

AU - Strindberg, Sophie

AU - Plum, Jakob

AU - Hall-Andersen, Jonatan

AU - Janfelt, Christian

AU - Nielsen, Line Hagner

AU - Müllertz, Anette

PY - 2019

Y1 - 2019

N2 - The influence of physiological factors on the solubility of drug compounds has been thoroughly investigated in humans. However, as these factors vary between species and since many in vivo studies are carried out in rats or mice, it has been difficult to establish sufficient in vitro in vivo relations. The aim of this study was to develop a physiologically relevant in vitro dissolution model simulating the gastrointestinal (GI) fluids of fasted rats and compare it to previously published in vitro and in vivo data. To develop the in vitro model, the pH was measured in situ in six segments of the GI tract of anesthetised rats, then the fluids from the stomach, the proximal and the distal small intestine were collected and characterized with regard to osmolality, and bile acid and phospholipid concentration. The pH and osmolality were found to increase throughout the GI tract. The bile acids and phospholipids were present in high concentrations in the proximal small intestine, and the bile acid concentration doubled in the distal part, where the phospholipid concentration decreased. Matrix-assisted laser desorption ionisation mass spectrometry imaging was applied on a cross section of the small intestine, to study which bile acids and phospholipid classes were present in the small intestine of rats. Both cholic acid, taurocholic acid and glycocholic acid were detected, and phosphatidylcholine (34:2) was found to be mainly present in the intestinal wall or mucus, whereas lysophosphatidylcholine (16:0) was also detected in the lumen. Based on these observations, biorelevant media were developed to simulate fluids in the stomach and the proximal part of the small intestine in fasted rats. The media were implemented in a two-step in vitro dissolution model, which was found to better predict the in vivo performance of furosemide, when compared to previously published in vitro and in vivo data.

AB - The influence of physiological factors on the solubility of drug compounds has been thoroughly investigated in humans. However, as these factors vary between species and since many in vivo studies are carried out in rats or mice, it has been difficult to establish sufficient in vitro in vivo relations. The aim of this study was to develop a physiologically relevant in vitro dissolution model simulating the gastrointestinal (GI) fluids of fasted rats and compare it to previously published in vitro and in vivo data. To develop the in vitro model, the pH was measured in situ in six segments of the GI tract of anesthetised rats, then the fluids from the stomach, the proximal and the distal small intestine were collected and characterized with regard to osmolality, and bile acid and phospholipid concentration. The pH and osmolality were found to increase throughout the GI tract. The bile acids and phospholipids were present in high concentrations in the proximal small intestine, and the bile acid concentration doubled in the distal part, where the phospholipid concentration decreased. Matrix-assisted laser desorption ionisation mass spectrometry imaging was applied on a cross section of the small intestine, to study which bile acids and phospholipid classes were present in the small intestine of rats. Both cholic acid, taurocholic acid and glycocholic acid were detected, and phosphatidylcholine (34:2) was found to be mainly present in the intestinal wall or mucus, whereas lysophosphatidylcholine (16:0) was also detected in the lumen. Based on these observations, biorelevant media were developed to simulate fluids in the stomach and the proximal part of the small intestine in fasted rats. The media were implemented in a two-step in vitro dissolution model, which was found to better predict the in vivo performance of furosemide, when compared to previously published in vitro and in vivo data.

KW - Biorelevant media

KW - Gastrointestinal fluids

KW - In vitro in vivo correlation

KW - Rats

U2 - 10.1016/j.ejpb.2019.07.007

DO - 10.1016/j.ejpb.2019.07.007

M3 - Journal article

C2 - 31288077

AN - SCOPUS:85068511341

VL - 142

SP - 307

EP - 314

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -

ID: 241099330