In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate

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In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate. / Thomas, Nicky; Richter, Katharina; Pedersen, Thomas B; Holm, René; Müllertz, Anette; Rades, Thomas.

In: A A P S Journal, Vol. 16, No. 3, 02.04.2014, p. 539-549.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Thomas, N, Richter, K, Pedersen, TB, Holm, R, Müllertz, A & Rades, T 2014, 'In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate', A A P S Journal, vol. 16, no. 3, pp. 539-549. https://doi.org/10.1208/s12248-014-9589-4

APA

Thomas, N., Richter, K., Pedersen, T. B., Holm, R., Müllertz, A., & Rades, T. (2014). In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate. A A P S Journal, 16(3), 539-549. https://doi.org/10.1208/s12248-014-9589-4

Vancouver

Thomas N, Richter K, Pedersen TB, Holm R, Müllertz A, Rades T. In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate. A A P S Journal. 2014 Apr 2;16(3):539-549. https://doi.org/10.1208/s12248-014-9589-4

Author

Thomas, Nicky ; Richter, Katharina ; Pedersen, Thomas B ; Holm, René ; Müllertz, Anette ; Rades, Thomas. / In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate. In: A A P S Journal. 2014 ; Vol. 16, No. 3. pp. 539-549.

Bibtex

@article{9d7c40e84ed74794866e1dcae9ab9283,
title = "In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate",
abstract = "The present study investigated the utility of in vitro lipolysis performance indicators drug solubilization and maximum supersaturation ratio (SR(M)) for their predictive use for the in vivo performance in a minipig model. The commercial Lipanthyl formulation and a series of LbDDS based on identical self-nanoemulsifying drug delivery systems (SNEDDS) containing 200 mg of fenofibrate, either dissolved or suspended, were subjected to combined gastric (pH 2) and intestinal (pH 6.5) in vitro lipolysis. Based on the solubilization profiles and SRM the rank-order SNEDDS (75{\%} drug load) > super-SNEDDS (150{\%} drug load, dissolved) = SNEDDS suspension (150{\%} drug load, partially suspended) > Lipanthyl was established, with an increased likelihood of drug precipitation above SR(M) > 3. The in vitro performance, however, was not reproduced in vivo in a minipig model as the mean plasma concentration over time curves of all LbDDS were comparable, independent of the initial physical state of the drug. There was no correlation between the area under the solubilization-time curves (AUC in vitro ) of the intestinal step and the AUC in vivo . The study suggests careful interpretation of in vitro performance criteria and revision of LbDDS optimization towards increased solubilization.",
author = "Nicky Thomas and Katharina Richter and Pedersen, {Thomas B} and Ren{\'e} Holm and Anette M{\"u}llertz and Thomas Rades",
year = "2014",
month = "4",
day = "2",
doi = "10.1208/s12248-014-9589-4",
language = "English",
volume = "16",
pages = "539--549",
journal = "A A P S Journal",
issn = "1550-7416",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - In Vitro Lipolysis Data Does Not Adequately Predict the In Vivo Performance of Lipid-Based Drug Delivery Systems Containing Fenofibrate

AU - Thomas, Nicky

AU - Richter, Katharina

AU - Pedersen, Thomas B

AU - Holm, René

AU - Müllertz, Anette

AU - Rades, Thomas

PY - 2014/4/2

Y1 - 2014/4/2

N2 - The present study investigated the utility of in vitro lipolysis performance indicators drug solubilization and maximum supersaturation ratio (SR(M)) for their predictive use for the in vivo performance in a minipig model. The commercial Lipanthyl formulation and a series of LbDDS based on identical self-nanoemulsifying drug delivery systems (SNEDDS) containing 200 mg of fenofibrate, either dissolved or suspended, were subjected to combined gastric (pH 2) and intestinal (pH 6.5) in vitro lipolysis. Based on the solubilization profiles and SRM the rank-order SNEDDS (75% drug load) > super-SNEDDS (150% drug load, dissolved) = SNEDDS suspension (150% drug load, partially suspended) > Lipanthyl was established, with an increased likelihood of drug precipitation above SR(M) > 3. The in vitro performance, however, was not reproduced in vivo in a minipig model as the mean plasma concentration over time curves of all LbDDS were comparable, independent of the initial physical state of the drug. There was no correlation between the area under the solubilization-time curves (AUC in vitro ) of the intestinal step and the AUC in vivo . The study suggests careful interpretation of in vitro performance criteria and revision of LbDDS optimization towards increased solubilization.

AB - The present study investigated the utility of in vitro lipolysis performance indicators drug solubilization and maximum supersaturation ratio (SR(M)) for their predictive use for the in vivo performance in a minipig model. The commercial Lipanthyl formulation and a series of LbDDS based on identical self-nanoemulsifying drug delivery systems (SNEDDS) containing 200 mg of fenofibrate, either dissolved or suspended, were subjected to combined gastric (pH 2) and intestinal (pH 6.5) in vitro lipolysis. Based on the solubilization profiles and SRM the rank-order SNEDDS (75% drug load) > super-SNEDDS (150% drug load, dissolved) = SNEDDS suspension (150% drug load, partially suspended) > Lipanthyl was established, with an increased likelihood of drug precipitation above SR(M) > 3. The in vitro performance, however, was not reproduced in vivo in a minipig model as the mean plasma concentration over time curves of all LbDDS were comparable, independent of the initial physical state of the drug. There was no correlation between the area under the solubilization-time curves (AUC in vitro ) of the intestinal step and the AUC in vivo . The study suggests careful interpretation of in vitro performance criteria and revision of LbDDS optimization towards increased solubilization.

U2 - 10.1208/s12248-014-9589-4

DO - 10.1208/s12248-014-9589-4

M3 - Journal article

C2 - 24687210

VL - 16

SP - 539

EP - 549

JO - A A P S Journal

JF - A A P S Journal

SN - 1550-7416

IS - 3

ER -

ID: 109627639