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Nonlinear absorption kinetics of self-emulsifying drug delivery systems (SEDDS) containing tocotrienols as lipophilic molecules: in vivo and in vitro studies.


ABSTRACT: Self-emulsifying drug delivery systems (SEDDS) have been broadly used to promote the oral absorption of poorly water-soluble drugs. The purpose of the current study was to evaluate the in vivo oral bioavailability of vitamin E isoforms, ?-tocotrienol (?-T3) and ?-tocotrienol (?-T3) administered as SEDDS, as compared to commercially available UNIQUE E® Tocotrienols capsules. Results from studies in rats showed that low dose treatment with ?-T3 (90%) and ?-T3 (10%) formulated SEDDS showed bioavailability of 31.5% and 332%, respectively. However, bioavailability showed a progressive decrease with increased treatment dose that displayed nonlinear absorption kinetics. Additional in vitro studies examining cellular uptake studies in Caco 2 cells revealed that the SEDDS formulation increased passive permeability of ?-T3 and ?-T3 by threefold as compared to the commercial capsule formulation. These studies also showed that free surfactants decreased ?-T3 and ?-T3 absorption. Specifically, combined treatment cremophor EL or labrasol with tocotrienols caused a 60-85% reduction in the cellular uptake of ?-T3 and ?-T3 and these effects appear to result from surfactant-induced inhibition of the ?-T3 and ?-T3 transport protein Niemann-Pick C1-like 1 (NPC1L1). In summary, results showed that SEDDS formulation significantly increases the absorption and bioavailability ?-T3 and ?-T3. However, this effect is self-limiting because treatment with increasing doses of SEDDS appears to be associated with a corresponding increase in free surfactants levels that directly and negatively impact tocotrienol transport protein function and results in nonlinear absorption kinetics and a progressive decrease in ?-T3 and ?-T3 absorption and bioavailability.

PROVIDER: S-EPMC3691427 | BioStudies | 2013-01-01T00:00:00Z

REPOSITORIES: biostudies

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