Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 102, Issue 2, Pages 565-578Publisher
WILEY-BLACKWELL
DOI: 10.1002/jps.23384
Keywords
lipid-based formulation; poorly water-soluble drugs; lipid-based drug delivery system; medium-chain triacylglyceride; long-chain triacylglyceride; lipids; oral absorption; formulation; bioavailability; in vitro model
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The influence of varying the amount of lipid co-administered with the drug on drug solubilisation and absorption is poorly understood. In the current study, the effect of lipid dose on the in vitro drug distribution is compared with the in vivo absorption of cinnarizine (CZ) when formulated using long-chain triacylglyceride (LCT) and medium-chain triacylglycerides (MCT). At a fixed druglipid ratio, in the closed in vitro model, the drug concentrations in the aqueous phase increased and decreased for MCT and LCT, respectively, with increasing lipid dose. However, in vivo, the oral bioavailability (F%) of CZ was independent of the quantity of lipid administered for both MCT and LCT, but was higher for LCT (32.1 +/- 2.3%) than for MCT (16.6 +/- 2.3%). Increasing the quantity of lipid relative to the dose of CZ resulted in an increase in the oral F% when the lipid mass was increased from 125 to 250 mg, but was no greater at 500 mg lipid dose. The results confirm the limitations of the in vitro model but positively indicate that the use of the rat as a pre-clinical model for studying the bioavailability of poorly water-soluble drugs is not compromised by the mass of formulation administered. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:565578, 2013
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