The effect of administered dose of lipid‐based formulations on the In Vitro and In Vivo performance of cinnarizine as a model poorly water‐soluble drug. Issue 2 (14th December 2012)

• Record Type: Journal Article
• Authors: Lee, Kathy Wai Yu; Porter, Christopher J. H.; Boyd, Ben J.
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 2(2013:Feb.)
• Page Start: 565
• Page End: 578
• Publication Date: 2012-12-14
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23384
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 <italic>in vitro</italic> drug distribution is compared with the <italic>in vivo</italic> absorption of cinnarizine (CZ) when formulated using long‐chain triacylglyceride (LCT) and medium‐chain triacylglycerides (MCT). At a fixed drug–lipid ratio, in the closed <italic>in vitro</italic> model, the drug concentrations in the aqueous phase increased and decreased for MCT and LCT, respectively, with increasing lipid dose. However, <italic>in vivo</italic>, the oral bioavailability (<italic>F</italic>%) 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 <italic>F</italic>% 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 <italic>in vitro</italic> 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. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:565–578, 2013</p> </abstract>