NDLI: Supersaturated Self-Nanoemulsifying Drug Delivery Systems (Super-SNEDDS) Enhance the Bioavailability of the Poorly Water-Soluble Drug Simvastatin in Dogs

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Supersaturated Self-Nanoemulsifying Drug Delivery Systems (Super-SNEDDS) Enhance the Bioavailability of the Poorly Water-Soluble Drug Simvastatin in Dogs

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Supersaturated Self-Nanoemulsifying Drug Delivery Systems (Super-SNEDDS) Enhance the Bioavailability of the Poorly Water-Soluble Drug Simvastatin in Dogs

Content Provider	Springer Nature Link
Author	Thomas, Nicky Holm, René Garmer, Mats Karlsson, Jens Jakob Müllertz, Anette Rades, Thomas
Copyright Year	2012
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.
Starting Page	219
Ending Page	227
Page Count	9
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	15
Issue Number	1
e-ISSN	15507416
Language	English
Publisher	Springer US
Publisher Date	2012-11-21
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	bioavailability in vitro digestion in vitro lipolysis simvastatin supersaturated self-nanoemusifying drug delivery systems (super-SNEDDS) poorly soluble drugs Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy
Content Type	Text
Resource Type	Article

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