Effects of Glycerides on the Intestinal Absorption of Cyclosporine A Using the In-Situ Mesenteric Vein Cannulated Rat Model

Mamdouh   M.   Ghorab; Heba   M.   Abdel-Salam; Mohamed   M.   Abdel-Moate

Abstract

The purpose of this study was to evaluate and compare the effect of glycerides with different fatty acid distributions (e.g. Arlacel 186, Capmul GMO and Captex 350) on Cyclosporine absorption in rat ileum segment using the modified single-pass intestinal perfusion with mesenteric vein cannulation. Drug concentration in the perfusate and blood plasma was analyzed by HPLC; and permeability coefficients were calculated from drug appearance in blood (Pblood) and disappearance from perfusate (Plumen). Particle size was measured using Malvern Zetasaizer 1000HSA. Rheologic properties were measured using Brookfield viscometer. The results show that the average particle sizes after dilution (100 folds) of formulae containing Arlacel 186, Capmul GMO and Captex 350 and containing 0.8 mM CsA were 260± 35.8, 130± 11.4 and 37.5± 6.0 nm, respectively. The polydispersity index was 0.6, 0.7 and 0.108 for formulations with Arlacel 186, Capmul GMO and Captex 350, respectively. CsA permeability coefficients (Pblood) calculated from drug appearance in the blood in presence of Arlacel 186, Capmul GMO and Captex 350 were 0.3x10-6, 1.0x10-6 and 1.7x10-6 cm2/sec, respectively. Phenol red was used as a water marker to determine net water absorption and secretion. Its constant concentration suggested that formulation did not alter intestinal water flux. From the results we can conclude that degree of glyceride esterification has a potential impact on the average particle size distribution and polydispersity of the formed micelles on dilution, which on turn contribute to the interaction between membrane and drug.

Keywords: cyclosporine a, medium chain glycerides, rat single-pass intestinal perfusion technique, intestinal drug permeability, absorption enhancers

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