Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug Simvastatin in dogs

Research output: Contribution to journalJournal articleResearchpeer-review

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Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug Simvastatin in dogs. / Thomas, Nicky; Holm, René; Garmer, Mats; Karlsson, Jens Jakob; Müllertz, Anette; Rades, Thomas.

In: A A P S Journal, Vol. 15, No. 1, 2013, p. 219-27.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Thomas, N, Holm, R, Garmer, M, Karlsson, JJ, Müllertz, A & Rades, T 2013, 'Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug Simvastatin in dogs', A A P S Journal, vol. 15, no. 1, pp. 219-27. https://doi.org/10.1208/s12248-012-9433-7

APA

Thomas, N., Holm, R., Garmer, M., Karlsson, J. J., Müllertz, A., & Rades, T. (2013). Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug Simvastatin in dogs. A A P S Journal, 15(1), 219-27. https://doi.org/10.1208/s12248-012-9433-7

Vancouver

Thomas N, Holm R, Garmer M, Karlsson JJ, Müllertz A, Rades T. Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug Simvastatin in dogs. A A P S Journal. 2013;15(1):219-27. https://doi.org/10.1208/s12248-012-9433-7

Author

Thomas, Nicky ; Holm, René ; Garmer, Mats ; Karlsson, Jens Jakob ; Müllertz, Anette ; Rades, Thomas. / Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug Simvastatin in dogs. In: A A P S Journal. 2013 ; Vol. 15, No. 1. pp. 219-27.

Bibtex

@article{753c24d0f52a4322824cb38d541c23d7,
title = "Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug Simvastatin in dogs",
abstract = "This study investigates the potential of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) to improve the bioavailability of poorly water-soluble drugs compared to conventional SNEDDS. Conventional SNEDDS contained simvastatin (SIM) at 75{\%} of the equilibrium solubility (S (eq)). Super-SNEDDS containing SIM at 150 and 200{\%} of S (eq) were produced by subjecting the SNEDDS preconcentrates to a heating and cooling cycle. The super-SNEDDS were physically stable over 10 months. During in vitro lipolysis of SNEDDS and super-SNEDDS the SIM concentration in the aqueous phase increased for the first 30 min almost proportional to the drug loads and amounts of preconcentrate employed. The 200{\%} drug-loaded super-SNEDDS generated an amorphous SIM precipitate at the end of in vitro lipolysis. In vivo, the relative bioavailability of SIM from super-SEDDDS increased significantly to 180¿±¿53.3{\%} (p¿=¿0.014) compared to the dosing of two capsules of (dose equivalent) 75{\%} drug-loaded SNEDDS. A significant increase in the terminal half-life of elimination was observed for super-SNEDDS (2.3¿±¿0.6 h) compared to conventional SNEDDS (1.4¿±¿0.3 h) as well as a decreased area under the curve ratio of the SIM metabolite simvastatin acid to the parent compound (0.57¿±¿0.20 and 0.90¿±¿0.3), possibly due to a combination of saturation effects on presystemic metabolising enzymes and prolonged absorption along the small intestine. In summary, this study demonstrated that super-SNEDDS are a viable formulation option to enhance the bioavailability of poorly water-soluble drugs such as simvastatin while reducing the pill burden by an increased drug load of SNEDDS.",
author = "Nicky Thomas and Ren{\'e} Holm and Mats Garmer and Karlsson, {Jens Jakob} and Anette M{\"u}llertz and Thomas Rades",
year = "2013",
doi = "10.1208/s12248-012-9433-7",
language = "English",
volume = "15",
pages = "219--27",
journal = "A A P S Journal",
issn = "1550-7416",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - Supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) enhance the bioavailability of the poorly water-soluble drug Simvastatin in dogs

AU - Thomas, Nicky

AU - Holm, René

AU - Garmer, Mats

AU - Karlsson, Jens Jakob

AU - Müllertz, Anette

AU - Rades, Thomas

PY - 2013

Y1 - 2013

N2 - This study investigates the potential of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) to improve the bioavailability of poorly water-soluble drugs compared to conventional SNEDDS. Conventional SNEDDS contained simvastatin (SIM) at 75% of the equilibrium solubility (S (eq)). Super-SNEDDS containing SIM at 150 and 200% of S (eq) were produced by subjecting the SNEDDS preconcentrates to a heating and cooling cycle. The super-SNEDDS were physically stable over 10 months. During in vitro lipolysis of SNEDDS and super-SNEDDS the SIM concentration in the aqueous phase increased for the first 30 min almost proportional to the drug loads and amounts of preconcentrate employed. The 200% drug-loaded super-SNEDDS generated an amorphous SIM precipitate at the end of in vitro lipolysis. In vivo, the relative bioavailability of SIM from super-SEDDDS increased significantly to 180¿±¿53.3% (p¿=¿0.014) compared to the dosing of two capsules of (dose equivalent) 75% drug-loaded SNEDDS. A significant increase in the terminal half-life of elimination was observed for super-SNEDDS (2.3¿±¿0.6 h) compared to conventional SNEDDS (1.4¿±¿0.3 h) as well as a decreased area under the curve ratio of the SIM metabolite simvastatin acid to the parent compound (0.57¿±¿0.20 and 0.90¿±¿0.3), possibly due to a combination of saturation effects on presystemic metabolising enzymes and prolonged absorption along the small intestine. In summary, this study demonstrated that super-SNEDDS are a viable formulation option to enhance the bioavailability of poorly water-soluble drugs such as simvastatin while reducing the pill burden by an increased drug load of SNEDDS.

AB - This study investigates the potential of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) to improve the bioavailability of poorly water-soluble drugs compared to conventional SNEDDS. Conventional SNEDDS contained simvastatin (SIM) at 75% of the equilibrium solubility (S (eq)). Super-SNEDDS containing SIM at 150 and 200% of S (eq) were produced by subjecting the SNEDDS preconcentrates to a heating and cooling cycle. The super-SNEDDS were physically stable over 10 months. During in vitro lipolysis of SNEDDS and super-SNEDDS the SIM concentration in the aqueous phase increased for the first 30 min almost proportional to the drug loads and amounts of preconcentrate employed. The 200% drug-loaded super-SNEDDS generated an amorphous SIM precipitate at the end of in vitro lipolysis. In vivo, the relative bioavailability of SIM from super-SEDDDS increased significantly to 180¿±¿53.3% (p¿=¿0.014) compared to the dosing of two capsules of (dose equivalent) 75% drug-loaded SNEDDS. A significant increase in the terminal half-life of elimination was observed for super-SNEDDS (2.3¿±¿0.6 h) compared to conventional SNEDDS (1.4¿±¿0.3 h) as well as a decreased area under the curve ratio of the SIM metabolite simvastatin acid to the parent compound (0.57¿±¿0.20 and 0.90¿±¿0.3), possibly due to a combination of saturation effects on presystemic metabolising enzymes and prolonged absorption along the small intestine. In summary, this study demonstrated that super-SNEDDS are a viable formulation option to enhance the bioavailability of poorly water-soluble drugs such as simvastatin while reducing the pill burden by an increased drug load of SNEDDS.

U2 - 10.1208/s12248-012-9433-7

DO - 10.1208/s12248-012-9433-7

M3 - Journal article

C2 - 23180162

VL - 15

SP - 219

EP - 227

JO - A A P S Journal

JF - A A P S Journal

SN - 1550-7416

IS - 1

ER -

ID: 43858744