摘要：

Theobjectiveofthisstudyistodevelop,invitroandinvivoevaluationofnovelapproachesforcontrolledreleaseofparoxetinehydrochloridehemihydrate(PHH)incomparisontopatentedformulationPAXILCR®tabletsofGlaxoSmithKline(Geomatrix™technology)Inoneoftheapproaches,hydrophiliccorematrixtabletscontaining85%ofthedosewerepreparedandfurthercoatedwithmethacrylicacidcopolymertodelaythereleaseAnimmediatereleasecoatingof15%wasgivenastopcoatThetabletswerefurtheroptionallycoatedusingethylcelluloseInthesecondapproach,hydrophobicmatrixcoretabletscontainingmetharylicacidcopolymerwerepreparedInthethirdapproach,PHHwasgranulatedwithentericpolymerandfurtherhydrophobicmatrixcoretabletswerepreparedTheeffectofpolymerconcentration,levelofentericcoatingondrugreleasewasevaluatedbyinvitrodissolutionstudybyvaryingdissolutionapparatusandtherotationspeedsItwasfoundthatincreaseinconcentrationofhighviscosityhydroxypropylmethylcellulose(HPMC)resultedinreductionofthereleaserateThedrugreleasewasobservedtobedependentonthelevelofentericcoatingandethylcellulosecoating,beingsloweratincreasedcoatingThereleasemechanismofPHHfollowedzero-ordershiftingtodissolutiondependentbytheincreaseofHPMCcontentTheformulationwasstablewithoutchangeindrugreleaserateInvivostudyinhumanvolunteersconfirmedthesimilaritybetweentestandinnovatorformulationsInconclusion,HPMC-basedmatrixtablets,whichwerefurthercoatedusingmethacrylicacidcopolymer,werefoundtobesuitablefortheformulationofsinglelayer-controlledreleasePHH

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