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Pharmaceutical Excipients Enhance Intestinal Absorption of Ganciclovir

Author: LiMing
Tutor: LiGao
School: Huazhong University of Science and Technology
Course: Pharmacy
Keywords: P-glycoprotein Pharmaceutical excipients Valgus intestinal sac Single pass perfusion method BCS-Ⅲ drugs
CLC: R96
Type: Master's thesis
Year: 2010
Downloads: 35
Quote: 0
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Abstract

P-glycoprotein is a broad spectrum to its substrate drugs and exogenous substances outside the discharge cell membrane transporter . It is abundantly expressed in the apical membrane of the intestinal epithelial cells , plays an important role in limiting drug absorption and oral bioavailability . Accessories inhibit P-glycoprotein -mediated drug efflux role is a unique method to promote intestinal absorption of drugs and increase the oral bioavailability of the drug . In this thesis probe drug ganciclovir for visits from the mucosal side to the serosal side of the transporter in isolated rat model and infiltration across the intestinal epithelium in vivo model to evaluate the F-68 Pharmaceutical Excipients , PEG-400, Tween-80 and EL-35 drug intestinal absorption . The results showed that : When the excipient concentration in the range of 0.1 ^{1 < / SUP > % ( w / v ) , in the valgus vitro gut sac model in each concentration group , all trials excipients can increase ganciclovir Wei transmembrane transport amount . F-68 to promote transhipment way similar to verapamil have regional differences , and PEG- 400 , Tween- 80 and EL-35 no significant regional differences promote absorption ; For in vivo perfusion model , first of all, we improved the model to create the small intestine of rat whole unidirectional lipophobic compound perfusion method to more accurately measure the permeability in the gut . The model data indicate that these excipients could significantly increase ganciclovir permeability in the intestine , its intestinal permeability coefficient by of 2.35 × ^{-6 < / SUP > cm · s or ^{-1 to obtain a significant increase (F-68 is 1.8-5.1 times ; PEG-400 is 2.6-4.8 times ; Tween-80 is about 2.8 times ; EL-35 is 6.7-13.4 times ). EL-35 and F-68 's role in a dose - dependent manner , PEG -400 and Tween -80 had no significant dose-dependent . These results indicate that the absorption promoting effect of these excipients to ganciclovir small intestine is very likely due to the inhibition of P-glycoprotein- mediated drug efflux transporter . Further, it is also possible to draw inferences through of these excipients different promote absorption way , blocking the P-glycoprotein and its substrate combined with a change in membrane fluidity of the two inhibitory mechanisms may also be included in the excipients on the P-glycoprotein inhibition of them. Wherein , F-68 and more involved former mechanism, and PEG- 400 , Tween -80 and EL-35 , may be mainly involving a suppression mechanism .}}}

Pharmaceutical Excipients Enhance Intestinal Absorption of Ganciclovir

Abstract

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