Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments. / Madsen, Cecilie Maria; Feng, Kung-I; Leithead, Andrew; Canfield, Nicole; Jørgensen, Søren Astrup; Müllertz, Anette; Rades, Thomas.

In: European Journal of Pharmaceutical Sciences, Vol. 111, 01.2018, p. 311-319.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Madsen, CM, Feng, K-I, Leithead, A, Canfield, N, Jørgensen, SA, Müllertz, A & Rades, T 2018, 'Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments', European Journal of Pharmaceutical Sciences, vol. 111, pp. 311-319. https://doi.org/10.1016/j.ejps.2017.10.003

APA

Madsen, C. M., Feng, K-I., Leithead, A., Canfield, N., Jørgensen, S. A., Müllertz, A., & Rades, T. (2018). Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments. European Journal of Pharmaceutical Sciences, 111, 311-319. https://doi.org/10.1016/j.ejps.2017.10.003

Vancouver

Madsen CM, Feng K-I, Leithead A, Canfield N, Jørgensen SA, Müllertz A et al. Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments. European Journal of Pharmaceutical Sciences. 2018 Jan;111:311-319. https://doi.org/10.1016/j.ejps.2017.10.003

Author

Madsen, Cecilie Maria ; Feng, Kung-I ; Leithead, Andrew ; Canfield, Nicole ; Jørgensen, Søren Astrup ; Müllertz, Anette ; Rades, Thomas. / Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments. In: European Journal of Pharmaceutical Sciences. 2018 ; Vol. 111. pp. 311-319.

Bibtex

@article{7799eaa8d7924aa3ab9ecd0919b5ef19,
title = "Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments",
abstract = "The composition of the human intestinal fluids varies both intra- and inter-individually. This will influence the solubility of orally administered drug compounds, and hence, the absorption and efficacy of compounds displaying solubility limited absorption. The purpose of this study was to assess the influence of simulated intestinal fluid (SIF) composition on the solubility of poorly soluble compounds. Using a Design of Experiments (DoE) approach, a set of 24 SIF was defined within the known compositions of human fasted state intestinal fluid. The SIF were composed of phospholipid, bile salt, and different pH, buffer capacities and osmolarities. On a small scale semi-robotic system, the solubility of 6 compounds (aprepitant, carvedilol, felodipine, fenofibrate, probucol, and zafirlukast) was determined in the 24 SIF. Compound specific models, describing key factors influencing the solubility of each compound, were identified. Although all models were different, the level of phospholipid and bile salt, the pH, and the interactions between these, had the biggest influences on solubility overall. Thus, a reduction of the DoE from five to three factors was possible (11-13 media), making DoE solubility studies feasible compared to single SIF solubility studies. Applying this DoE approach will lead to a better understanding of the impact of intestinal fluid composition on the solubility of a given drug compound.",
keywords = "Journal Article",
author = "Madsen, {Cecilie Maria} and Kung-I Feng and Andrew Leithead and Nicole Canfield and J{\o}rgensen, {S{\o}ren Astrup} and Anette M{\"u}llertz and Thomas Rades",
note = "Copyright {\circledC} 2017. Published by Elsevier B.V.",
year = "2018",
month = "1",
doi = "10.1016/j.ejps.2017.10.003",
language = "English",
volume = "111",
pages = "311--319",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Effect of composition of simulated intestinal media on the solubility of poorly soluble compounds investigated by design of experiments

AU - Madsen, Cecilie Maria

AU - Feng, Kung-I

AU - Leithead, Andrew

AU - Canfield, Nicole

AU - Jørgensen, Søren Astrup

AU - Müllertz, Anette

AU - Rades, Thomas

N1 - Copyright © 2017. Published by Elsevier B.V.

PY - 2018/1

Y1 - 2018/1

N2 - The composition of the human intestinal fluids varies both intra- and inter-individually. This will influence the solubility of orally administered drug compounds, and hence, the absorption and efficacy of compounds displaying solubility limited absorption. The purpose of this study was to assess the influence of simulated intestinal fluid (SIF) composition on the solubility of poorly soluble compounds. Using a Design of Experiments (DoE) approach, a set of 24 SIF was defined within the known compositions of human fasted state intestinal fluid. The SIF were composed of phospholipid, bile salt, and different pH, buffer capacities and osmolarities. On a small scale semi-robotic system, the solubility of 6 compounds (aprepitant, carvedilol, felodipine, fenofibrate, probucol, and zafirlukast) was determined in the 24 SIF. Compound specific models, describing key factors influencing the solubility of each compound, were identified. Although all models were different, the level of phospholipid and bile salt, the pH, and the interactions between these, had the biggest influences on solubility overall. Thus, a reduction of the DoE from five to three factors was possible (11-13 media), making DoE solubility studies feasible compared to single SIF solubility studies. Applying this DoE approach will lead to a better understanding of the impact of intestinal fluid composition on the solubility of a given drug compound.

AB - The composition of the human intestinal fluids varies both intra- and inter-individually. This will influence the solubility of orally administered drug compounds, and hence, the absorption and efficacy of compounds displaying solubility limited absorption. The purpose of this study was to assess the influence of simulated intestinal fluid (SIF) composition on the solubility of poorly soluble compounds. Using a Design of Experiments (DoE) approach, a set of 24 SIF was defined within the known compositions of human fasted state intestinal fluid. The SIF were composed of phospholipid, bile salt, and different pH, buffer capacities and osmolarities. On a small scale semi-robotic system, the solubility of 6 compounds (aprepitant, carvedilol, felodipine, fenofibrate, probucol, and zafirlukast) was determined in the 24 SIF. Compound specific models, describing key factors influencing the solubility of each compound, were identified. Although all models were different, the level of phospholipid and bile salt, the pH, and the interactions between these, had the biggest influences on solubility overall. Thus, a reduction of the DoE from five to three factors was possible (11-13 media), making DoE solubility studies feasible compared to single SIF solubility studies. Applying this DoE approach will lead to a better understanding of the impact of intestinal fluid composition on the solubility of a given drug compound.

KW - Journal Article

U2 - 10.1016/j.ejps.2017.10.003

DO - 10.1016/j.ejps.2017.10.003

M3 - Journal article

C2 - 28986196

VL - 111

SP - 311

EP - 319

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

ER -

ID: 185403176