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1、StudyonthephasesolubilityofalI-trans-retinoicacid/cyclodextrininclusioncompIexandtheeffectsofwater-soIubIepoIymerAuthorChenZhongjian'QiJianping•IntroductionAIl-trans-retinoicacid(ATRA),whichisaintermediateproductofVitaminAinhumanmetaboIism,hasbeenwidelyusedinthetreat
2、mentofskindiseasesandtumors1151.However,ATRAsIowsoIubIiIityinwater,instabiIityinIightorheat,andsusceptibiIitytooxidationhaveseverelyIimiteditsproductionanduse.Moreover,inthetreatmerrtofskindiseases,thetherapeuticdoseofATRAisclosetoitstoxicdose,whichoftenleadstosomead
3、versereactionsIikedecrustation,,WuWei1,LuYi"Address1SchooIofpharmacy,FudanUniversity,Shanghai,China,201203PharmacyDepartment,ShanghaiSkinDiseaseHospitai,ShangHai200443*CorrespondenceAuthorEmaiI66645445@qq.ComAbstractThroughphasesolubilitystudy,weinvestigatedthesoIubi
4、IizationeffectsofeyeIodextrin(CD)onaIl~trans~retinoicacid(ATRA).Westudiedtheeffectsofwater-solublepolymersonthephasesolubiIityofATRA/CDinclusioncomplex,whichwerebasedoncommonusedgelmatrix・Accordingtothestudy,ATRAformed1:1incIusioncompIexwithci-CD,B-CDandY一CD.ATRAcouI
5、dform1:1inelusioncomplexeswith2-hydroxypropyI-B-eyeIodextrin(HP-B-CD)when30HP-B-CDconcentrationwasbelow6%.Otherwise,itcouIdform1:2inclusioncompIex.ThemaximumsoIubiIityofATRA,inaqueoussolutionofa一CD,P-CD,Y-CDandHP-0-CD,was5.5、15.1>24.2and34.6timesthatinpurewater・Thead
6、ditionofwater-solubIepolymerscouldfurtherincreasethestabiIityconstantofATRA/0-CDinclusioncompIexandthesolubilityofATRA,amongwhich,CMC-Nashowedthemostsignificarrteffect.Withtheadditionof0.5%CMC-NatoB-CDsolution,thestabiIityconstantofATRA/0-CDinclusionwasincreased4.6ti
7、mes,whilethemaximumsoIubiIityofATRAwasincreased247.4timesthatinwaterand16.4timesthatin1.8%P-CDsolutionrespectively.WithCMC-Naasmatrixand3一CDassoIubiIizer,thetopicaIpreparationofATRAwiIIbepreparedwithincreasingunitconcerntrationofATRAanddecreasingpotentiaIadverseeffec
8、ts・Keywords:pharmaceutics;all~trans-retinoicacid;eyeIodextrin;CMC-Na;phasesolubiIity;water-solublepoIymer.erythema,skinburning,andt
