Effect of Common Excipients on Intestinal Drug Absorption in Wistar Rats

Abstract

Theaimof thepresentpaper is tostudytheeffectofcommonexcipientsonthepermeabilityofatenolol (asdrug absorbedmainlybypassivediffusion)andrhodamine(asP-glycoproteinsubstrate).Theapparentpermeabilitywasmeasuredbyan insituperfusionmethod inWistar ratsusing theclosed loopDoluisio’smethod. Permeabilityvalueswerecharacterized inthe absence andpresenceof 18commonlyusedexcipients. Excipient concentrationswere selectedbasedon the amounts inoral immediate releasedosage forms,which failedthe testduring thehumanbioequivalence studies.Atenololwas studiedwithand withoutexcipients inthewholesmall intestine,whereasrhodaminewastestedinthreedifferent intestinal segmentstoaccount for thedifferential expressionof P-glycoprotein, and itwas further on tested in the ileum, in thepresenceof excipients. Atenolol presentedhigherpermeabilityvalueswhenitwasadministeredwithcolloidal silica, croscarmellose,hydroxypropylmethylcellulose (HPMC),magnesiumstearate,MgCO3, poly(ethyleneglycol)400, poly(vinylpyrrolidone), sorbitol, starch, andTiO2 rhodamine showedhigherpermeabilityvalueswhenitwasadministeredwithcroscarmelloseandHPMC.Ontheonehand, themechanismsof actionwerenotdiscerniblewiththeproposedexperiments.Ontheotherhand, commercial formulationsdonotpresentasingle excipientbutseveral,whichcancounteracttheireffects.Theinsituperfusiontechniquecanbeusefulforapreliminaryscreeningand riskanalysis,whilethe invivopharmacokineticresultswouldbeneededtodefineconclusiveeffects.