In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems

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In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems. / Sassene, P J; Michaelsen, M H; Mosgaard, M D; Jensen, M.K.; Van Den Broek, E; Wasan, K M; Mu, H; Rades, T; Müllertz, A.

In: Molecular Pharmaceutics, Vol. 13, No. 10, 03.10.2016, p. 3417-3426.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Sassene, PJ, Michaelsen, MH, Mosgaard, MD, Jensen, MK, Van Den Broek, E, Wasan, KM, Mu, H, Rades, T & Müllertz, A 2016, 'In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems', Molecular Pharmaceutics, vol. 13, no. 10, pp. 3417-3426. https://doi.org/10.1021/acs.molpharmaceut.6b00413

APA

Sassene, P. J., Michaelsen, M. H., Mosgaard, M. D., Jensen, M. K., Van Den Broek, E., Wasan, K. M., ... Müllertz, A. (2016). In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems. Molecular Pharmaceutics, 13(10), 3417-3426. https://doi.org/10.1021/acs.molpharmaceut.6b00413

Vancouver

Sassene PJ, Michaelsen MH, Mosgaard MD, Jensen MK, Van Den Broek E, Wasan KM et al. In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems. Molecular Pharmaceutics. 2016 Oct 3;13(10):3417-3426. https://doi.org/10.1021/acs.molpharmaceut.6b00413

Author

Sassene, P J ; Michaelsen, M H ; Mosgaard, M D ; Jensen, M.K. ; Van Den Broek, E ; Wasan, K M ; Mu, H ; Rades, T ; Müllertz, A. / In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems. In: Molecular Pharmaceutics. 2016 ; Vol. 13, No. 10. pp. 3417-3426.

Bibtex

@article{61da8e41910c4c0fa7fffd115616cc79,
title = "In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems",
abstract = "Precipitation of poorly water-soluble drugs from lipid-based drug delivery systems (LbDDS) has been studied extensively during in vitro lipolysis but has never been shown in vivo. The aim of this study was therefore to investigate if drug precipitation can occur from LbDDS during transit of the gastrointestinal tract in vivo. Rats were administered 300 μL of either of two LbDDS (LbDDS I and LbDDS II) loaded with danazol or fenofibrate (or paracetamol to assess gastric emptying). The rats were euthanized at various time points after administration of both LbDDS containing either drug, and the contents of the stomach and proximal part of the small intestine were harvested. The contents were analyzed for crystalline drug by X-ray powder diffraction and polarized light microscopy. No drug precipitation was evident in the stomach or the intestine after administration of LbDDS I containing danazol at the tested time points. Fenofibrate precipitation was absent in the stomach initially after administration of LbDDS I, but was evident in the stomach 90 min after dosing. No crystalline fenofibrate was observed in the intestine. Danazol and fenofibrate precipitation was evident in the stomach following administration of LbDDS II containing either drug, but not in the intestine at the tested time point. Drug precipitation from LbDDS was observed in the stomach, but not in the intestine, which is contrary to what in vitro lipolysis data (obtained under human GI conditions) suggests. Thus, precipitation of drugs from LbDDS in vivo in rats is much lower than might be anticipated from in vitro lipolysis data.",
author = "Sassene, {P J} and Michaelsen, {M H} and Mosgaard, {M D} and M.K. Jensen and {Van Den Broek}, E and Wasan, {K M} and H Mu and T Rades and A M{\"u}llertz",
year = "2016",
month = "10",
day = "3",
doi = "10.1021/acs.molpharmaceut.6b00413",
language = "English",
volume = "13",
pages = "3417--3426",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - In Vivo Precipitation of Poorly Soluble Drugs from Lipid-Based Drug Delivery Systems

AU - Sassene, P J

AU - Michaelsen, M H

AU - Mosgaard, M D

AU - Jensen, M.K.

AU - Van Den Broek, E

AU - Wasan, K M

AU - Mu, H

AU - Rades, T

AU - Müllertz, A

PY - 2016/10/3

Y1 - 2016/10/3

N2 - Precipitation of poorly water-soluble drugs from lipid-based drug delivery systems (LbDDS) has been studied extensively during in vitro lipolysis but has never been shown in vivo. The aim of this study was therefore to investigate if drug precipitation can occur from LbDDS during transit of the gastrointestinal tract in vivo. Rats were administered 300 μL of either of two LbDDS (LbDDS I and LbDDS II) loaded with danazol or fenofibrate (or paracetamol to assess gastric emptying). The rats were euthanized at various time points after administration of both LbDDS containing either drug, and the contents of the stomach and proximal part of the small intestine were harvested. The contents were analyzed for crystalline drug by X-ray powder diffraction and polarized light microscopy. No drug precipitation was evident in the stomach or the intestine after administration of LbDDS I containing danazol at the tested time points. Fenofibrate precipitation was absent in the stomach initially after administration of LbDDS I, but was evident in the stomach 90 min after dosing. No crystalline fenofibrate was observed in the intestine. Danazol and fenofibrate precipitation was evident in the stomach following administration of LbDDS II containing either drug, but not in the intestine at the tested time point. Drug precipitation from LbDDS was observed in the stomach, but not in the intestine, which is contrary to what in vitro lipolysis data (obtained under human GI conditions) suggests. Thus, precipitation of drugs from LbDDS in vivo in rats is much lower than might be anticipated from in vitro lipolysis data.

AB - Precipitation of poorly water-soluble drugs from lipid-based drug delivery systems (LbDDS) has been studied extensively during in vitro lipolysis but has never been shown in vivo. The aim of this study was therefore to investigate if drug precipitation can occur from LbDDS during transit of the gastrointestinal tract in vivo. Rats were administered 300 μL of either of two LbDDS (LbDDS I and LbDDS II) loaded with danazol or fenofibrate (or paracetamol to assess gastric emptying). The rats were euthanized at various time points after administration of both LbDDS containing either drug, and the contents of the stomach and proximal part of the small intestine were harvested. The contents were analyzed for crystalline drug by X-ray powder diffraction and polarized light microscopy. No drug precipitation was evident in the stomach or the intestine after administration of LbDDS I containing danazol at the tested time points. Fenofibrate precipitation was absent in the stomach initially after administration of LbDDS I, but was evident in the stomach 90 min after dosing. No crystalline fenofibrate was observed in the intestine. Danazol and fenofibrate precipitation was evident in the stomach following administration of LbDDS II containing either drug, but not in the intestine at the tested time point. Drug precipitation from LbDDS was observed in the stomach, but not in the intestine, which is contrary to what in vitro lipolysis data (obtained under human GI conditions) suggests. Thus, precipitation of drugs from LbDDS in vivo in rats is much lower than might be anticipated from in vitro lipolysis data.

U2 - 10.1021/acs.molpharmaceut.6b00413

DO - 10.1021/acs.molpharmaceut.6b00413

M3 - Journal article

C2 - 27533712

VL - 13

SP - 3417

EP - 3426

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 10

ER -

ID: 168937639