Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3 : understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations. / Williams, Hywel D; Sassene, Philip; Kleberg, Karen; Calderone, Marilyn; Igonin, Annabel; Jule, Eduardo; Vertommen, Jan; Blundell, Ross; Benameur, Hassan; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H; LFCS Consortium.

In: Pharmaceutical Research, Vol. 30, No. 12, 12.2013, p. 3059-76.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Williams, HD, Sassene, P, Kleberg, K, Calderone, M, Igonin, A, Jule, E, Vertommen, J, Blundell, R, Benameur, H, Müllertz, A, Pouton, CW, Porter, CJH & LFCS Consortium 2013, 'Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations', Pharmaceutical Research, vol. 30, no. 12, pp. 3059-76. https://doi.org/10.1007/s11095-013-1038-z

APA

Williams, H. D., Sassene, P., Kleberg, K., Calderone, M., Igonin, A., Jule, E., Vertommen, J., Blundell, R., Benameur, H., Müllertz, A., Pouton, C. W., Porter, C. J. H., & LFCS Consortium (2013). Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations. Pharmaceutical Research, 30(12), 3059-76. https://doi.org/10.1007/s11095-013-1038-z

Vancouver

Williams HD, Sassene P, Kleberg K, Calderone M, Igonin A, Jule E et al. Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations. Pharmaceutical Research. 2013 Dec;30(12):3059-76. https://doi.org/10.1007/s11095-013-1038-z

Author

Williams, Hywel D ; Sassene, Philip ; Kleberg, Karen ; Calderone, Marilyn ; Igonin, Annabel ; Jule, Eduardo ; Vertommen, Jan ; Blundell, Ross ; Benameur, Hassan ; Müllertz, Anette ; Pouton, Colin W ; Porter, Christopher J H ; LFCS Consortium. / Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3 : understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations. In: Pharmaceutical Research. 2013 ; Vol. 30, No. 12. pp. 3059-76.

Bibtex

@article{a77a8fd1f3b7487fb8a467dd50f8d571,
title = "Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations",
abstract = "PURPOSE: Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs.METHODS: Type I, II, IIIA/B LBFs containing medium-chain (MC) or long-chain (LC) lipids, and lipid-free Type IV LBF incorporating different doses of fenofibrate or tolfenamic acid were digested in vitro in a simulated intestinal medium. The degree of supersaturation was assessed through comparison of drug concentrations in aqueous digestion phases (APDIGEST) during LBF digestion and the equilibrium drug solubility in the same phases.RESULTS: Increasing fenofibrate or tolfenamic acid drug loads (i.e., dose) had negligible effects on LC LBF performance during digestion, but promoted drug crystallization (confirmed by XRPD) from MC and Type IV LBF. Drug crystallization was only evident in instances when the calculated maximum supersaturation ratio (SR(M)) was >3. This threshold SR(M) value was remarkably consistent across all LBF and was also consistent with previous studies with danazol.CONCLUSIONS: The maximum supersaturation ratio (SR(M)) provides an indication of the supersaturation 'pressure' exerted by formulation digestion and is strongly predictive of the likelihood of drug precipitation in vitro. This may also prove effective in discriminating the in vivo performance of LBFs.",
keywords = "Chemical Precipitation, Crystallization, Digestion, Fenofibrate, Humans, Hypolipidemic Agents, Intestines, Lipid Metabolism, Lipids, Pharmaceutical Vehicles, Solubility, ortho-Aminobenzoates",
author = "Williams, {Hywel D} and Philip Sassene and Karen Kleberg and Marilyn Calderone and Annabel Igonin and Eduardo Jule and Jan Vertommen and Ross Blundell and Hassan Benameur and Anette M{\"u}llertz and Pouton, {Colin W} and Porter, {Christopher J H} and {LFCS Consortium}",
year = "2013",
month = dec,
doi = "10.1007/s11095-013-1038-z",
language = "English",
volume = "30",
pages = "3059--76",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer",
number = "12",

}

RIS

TY - JOUR

T1 - Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3

T2 - understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations

AU - Williams, Hywel D

AU - Sassene, Philip

AU - Kleberg, Karen

AU - Calderone, Marilyn

AU - Igonin, Annabel

AU - Jule, Eduardo

AU - Vertommen, Jan

AU - Blundell, Ross

AU - Benameur, Hassan

AU - Müllertz, Anette

AU - Pouton, Colin W

AU - Porter, Christopher J H

AU - LFCS Consortium

PY - 2013/12

Y1 - 2013/12

N2 - PURPOSE: Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs.METHODS: Type I, II, IIIA/B LBFs containing medium-chain (MC) or long-chain (LC) lipids, and lipid-free Type IV LBF incorporating different doses of fenofibrate or tolfenamic acid were digested in vitro in a simulated intestinal medium. The degree of supersaturation was assessed through comparison of drug concentrations in aqueous digestion phases (APDIGEST) during LBF digestion and the equilibrium drug solubility in the same phases.RESULTS: Increasing fenofibrate or tolfenamic acid drug loads (i.e., dose) had negligible effects on LC LBF performance during digestion, but promoted drug crystallization (confirmed by XRPD) from MC and Type IV LBF. Drug crystallization was only evident in instances when the calculated maximum supersaturation ratio (SR(M)) was >3. This threshold SR(M) value was remarkably consistent across all LBF and was also consistent with previous studies with danazol.CONCLUSIONS: The maximum supersaturation ratio (SR(M)) provides an indication of the supersaturation 'pressure' exerted by formulation digestion and is strongly predictive of the likelihood of drug precipitation in vitro. This may also prove effective in discriminating the in vivo performance of LBFs.

AB - PURPOSE: Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs.METHODS: Type I, II, IIIA/B LBFs containing medium-chain (MC) or long-chain (LC) lipids, and lipid-free Type IV LBF incorporating different doses of fenofibrate or tolfenamic acid were digested in vitro in a simulated intestinal medium. The degree of supersaturation was assessed through comparison of drug concentrations in aqueous digestion phases (APDIGEST) during LBF digestion and the equilibrium drug solubility in the same phases.RESULTS: Increasing fenofibrate or tolfenamic acid drug loads (i.e., dose) had negligible effects on LC LBF performance during digestion, but promoted drug crystallization (confirmed by XRPD) from MC and Type IV LBF. Drug crystallization was only evident in instances when the calculated maximum supersaturation ratio (SR(M)) was >3. This threshold SR(M) value was remarkably consistent across all LBF and was also consistent with previous studies with danazol.CONCLUSIONS: The maximum supersaturation ratio (SR(M)) provides an indication of the supersaturation 'pressure' exerted by formulation digestion and is strongly predictive of the likelihood of drug precipitation in vitro. This may also prove effective in discriminating the in vivo performance of LBFs.

KW - Chemical Precipitation

KW - Crystallization

KW - Digestion

KW - Fenofibrate

KW - Humans

KW - Hypolipidemic Agents

KW - Intestines

KW - Lipid Metabolism

KW - Lipids

KW - Pharmaceutical Vehicles

KW - Solubility

KW - ortho-Aminobenzoates

U2 - 10.1007/s11095-013-1038-z

DO - 10.1007/s11095-013-1038-z

M3 - Journal article

C2 - 23661145

VL - 30

SP - 3059

EP - 3076

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 12

ER -

ID: 120402611