RUUHVSRQGHQFH UHPLmRFKRRORIKDUPDFHXWLFDOFLHQFHV RGRYLDUDUDTXDUDDNPUDUDTXDUDUDLO PDLOSJUHPLDRIFIDUXQHVSEU HYLHZ Brazilian Journal of Pharmaceutical Sciences vol PDF document - DocSlides

RUUHVSRQGHQFH UHPLmRFKRRORIKDUPDFHXWLFDOFLHQFHV RGRYLDUDUDTXDUDDNPUDUDTXDUDUDLO PDLOSJUHPLDRIFIDUXQHVSEU HYLHZ Brazilian Journal of Pharmaceutical Sciences vol PDF document - DocSlides

2014-12-14 128K 128 0 0

Description

46 n 1 janmar 2010 Mucoadhesive drug delivery systems OiYLD57347KLYD57347DUYDOKR 57359573470DUFRV57347XFLDQR57347UXVFKL 5DXO57347HVDU57347YDQJHOLVWD 0DULD573473DOPLUD57347D57536RQ57347UHPLmR 3KDUPDFHXWLFDO573476FLHQFHV573473RVWJUDGXDWH573473URJUDP57 ID: 23637

Direct Link: Link:https://www.docslides.com/mitsue-stanley/ruuhvsrqghqfh-uhplmrfkrrorikdupdfhxwlfdoflhqfhv Embed code:

Download this pdf

DownloadNote - The PPT/PDF document "RUUHVSRQGHQFH UHPLmRFKRRORIKDUPDFHXWLFDO..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.

Presentations text content in RUUHVSRQGHQFH UHPLmRFKRRORIKDUPDFHXWLFDOFLHQFHV RGRYLDUDUDTXDUDDNPUDUDTXDUDUDLO PDLOSJUHPLDRIFIDUXQHVSEU HYLHZ Brazilian Journal of Pharmaceutical Sciences vol


Page 1
&RUUHVSRQGHQFH 03'*UHPLmR6FKRRORI3KDUPDFHXWLFDO6FLHQFHV 81(635RGRYLD$UDUDTXDUD-D~NP$UDUDTXDUD63%UD]LO (PDLOSJUHPLDR#IFIDUXQHVSEU 5HYLHZ Brazilian Journal of Pharmaceutical Sciences vol. 46, n. 1, jan./mar., 2010 Mucoadhesive drug delivery systems )OiYLD&KLYD&DUYDOKR 0DUFRV/XFLDQR%UXVFKL 5DXO&HVDU(YDQJHOLVWD 0DULD3DOPLUD'DRQ*UHPLmR 3KDUPDFHXWLFDO6FLHQFHV3RVWJUDGXDWH3URJUDP6FKRRORI3KDUPDFHXWLFDO6FLHQFHV6mR3DXOR6WDWH8QLYHUVLW\81(63 'HSDUWPHQWRI3KDUPDF\6WDWH8QLYHUVLW\RI0DULQJi8(0 'HSDUWPHQWRI'UXJVDQG3KDUPDFHXWLFDOV6FKRRORI 3KDUPDFHXWLFDO6FLHQFHV6mR3DXOR6WDWH8QLYHUVLW\81(63 'UXJDFWLRQVFDQEHLPSURYHGE\GHYHORSLQJQHZGUXJGHOLYHU\V\VWHPVVXFKDVWKHPXFRDGKHVLYH V\VWHP7KHVHV\VWHPVUHPDLQLQFORVHFRQWDFWZLWKWKHDEVRUSWLRQWLVVXHWKHPXFRXVPHPEUDQHUHOHDVLQJ WKHGUXJDWWKHDFWLRQVLWHOHDGLQJWRDELRDYDLODELOLW\LQFUHDVHDQGERWKORFDODQGV\VWHPLFHIIHFWV 0XFRDGKHVLRQLVFXUUHQWO\H[SODLQHGE\VL[WKHRULHVHOHFWURQLFDGVRUSWLRQZHWWDELOLW\GLIIXVLRQIUDFWXUH DQGPHFKDQLFDO6HYHUDO LQYLWUR DQG LQYLYR PHWKRGRORJLHVDUHSURSRVHGIRUVWXG\LQJLWVPHFKDQLVPV +RZHYHUPXFRDGKHVLRQLVQRW\HWZHOOXQGHUVWRRG7KHDLPRIWKLVVWXG\ZDVWRUHYLHZWKHPHFKDQLVPV DQGWKHRULHVLQYROYHGLQPXFRDGKHVLRQDVZHOODVWRGHVFULEHWKHPRVWXVHGPHWKRGRORJLHVDQGSRO\PHUV LQPXFRDGKHVLYHGUXJGHOLYHU\V\VWHPV 8QLWHUPV 0XFRDGKHVLRQ%LRDGKHVLRQ0XFRDGKHVLYHV\VWHPV'UXJVGHOLYHU\ 2HIHLWRGHIiUPDFRVSRGHVHUSRWHQFLDOL]DGRDWUDYpVGRGHVHQYROYLPHQWRGHQRYRVVLVWHPDVGHOLEHUDomR FRPRRVVLVWHPDVPXFRDGHVLYRV(VWHVVLVWHPDVSHUPDQHFHPHPFRQWDWRtQWLPRFRPRWHFLGRGHDEVRUomR DVPXFRVDVOLEHUDQGRRIiUPDFRQRORFDOGHDomRFRPRFRQVHTXHQWHDXPHQWRGDELRGLVSRQLELOLGDGH SRGHQGRSURPRYHUHIHLWRVORFDLVHVLVWrPLFRV$PXFRDGHVmRDWXDOPHQWHpH[SOLFDGDSRUVHLVWHRULDV DHOHWU{QLFDGDDGVRUomRGDPROKDELOLGDGHGDGLIXVmRGDIUDWXUDHDPHFkQLFD3DUDHVWXGDUVHXV PHFDQLVPRVHTXDQWLFiODVmRSURSRVWDVYiULDVPHWRGRORJLDV LQYLWUR H LQYLYR 3RUpPDPXFRDGHVmR DLQGDQmRpWRWDOPHQWHFRPSUHHQGLGD(VVHWUDEDOKRWHPSRUREMHWLYRUHYLVDURVPHFDQLVPRVHDVWHRULDV HQYROYLGDVQDPXFRDGHVmRDOpPGHGHVFUHYHUDVPHWRGRORJLDVHRVSROtPHURVPDLVXWLOL]DGRVHPVLVWHPDV PXFRDGHVLYRVSDUDOLEHUDomRGHIiUPDFRV 8QLWHUPRV 0XFRDGHVmR%LRDGHVmR6LVWHPDVPXFRDGHVLYRV)iUPDFRVOLEHUDomR INTRODUCTION 7KHHIIHFWRIDGUXJFDQQRZEHUHLQIRUFHGDVDUHVXOW RIWKHGHYHORSPHQWRIQHZUHOHDVHV\VWHPV&RQWUROOHGUH OHDVHFRQVLVWVRIWHFKQLTXHVWKDWPDNHWKHDFWLYHFKHPLFDO DJHQWVDYDLODEOHIRUDWDUJHWSURYLGLQJDQDGHTXDWHUHOHDVH UDWHDQGGXUDWLRQWRSURGXFHWKHGHVLUHGHIIHFW7KHPDLQ FRQWUROOHGGUXJGHOLYHU\V\VWHPVFXUUHQWO\DYDLODEOHLQFOXGH PDWULFHVSHOOHWVRDWLQJV\VWHPVOLSRVRPHVPLFURHPXO VLRQVOLTXLGFU\VWDOVVROLGGLVSHUVLRQVQDQRVXVSHQVLRQV WUDQVGHUPDOV\VWHPVF\FORGH[WULQLQFOXVLRQFRPSOH[HV RVPRWLFSXPSVDQGELRDGKHVLYHV\VWHPV:LVH %LRDGKHVLRQFDQEHGHQHGDVWKHVWDWHLQZKLFKWZR PDWHULDOVDWOHDVWRQHRIZKLFKLVELRORJLFDOLQQDWXUHDUH PDLQWDLQHGWRJHWKHUIRUDSURORQJHGWLPHSHULRGE\PHDQV RILQWHUIDFLDOIRUFHV6PDUW'XULQJWKHVWKLV FRQFHSWEHJDQWREHDSSOLHGWRGUXJGHOLYHU\V\VWHPV,W FRQVLVWVRIWKHLQFRUSRUDWLRQRIDGKHVLYHPROHFXOHVLQWR VRPHNLQGRISKDUPDFHXWLFDOIRUPXODWLRQLQWHQGHGWR VWD\LQFORVHFRQWDFWZLWKWKHDEVRUSWLRQWLVVXHUHOHDVLQJ WKHGUXJQHDUWRWKHDFWLRQVLWHWKHUHE\LQFUHDVLQJLWV ELRDYDLODELOLW\DQGSURPRWLQJORFDORUV\VWHPLFHIIHFWV +lJHUVWU|P:RRGOH\$QH[WHQVLYHUHYLHZ RQPXFRDGKHVLYHV\VWHPVZDVFRPSLOHGE\$QGUHZV /DYHUW\DQG-RQHV 7KHSRWHQWLDOXVHIRUPXFRDGKHVLYHV\VWHPVDVGUXJ FDUULHUVOLHVLQLWVSURORQJDWLRQRIWKHUHVLGHQFHWLPHDW WKHDEVRUSWLRQVLWHDOORZLQJLQWHQVLHGFRQWDFWZLWKWKH
Page 2
)&&DUYDOKR0/%UXVFKL5&(YDQJHOLVWD03'*UHPLmR HSLWKHOLDOEDUULHU+lJHUVWU|P 2QWKHRWKHUKDQG DGKHVLRQRISUHSDUDWLRQVRQWRPXFRXVPHPEUDQHFDQEH LPSDLUHGE\WKHPXFRFLOLDU\FOHDUDQFHV\VWHP7KLVFOHD UDQFHDQDWXUDOGHIHQVHPHFKDQLVPRIWKHERG\DJDLQVWWKH GHSRVLWLRQRILPSXULWLHVRQWRWKHPXFRXVPHPEUDQHFDQ DOVRUHPRYHWKHSUHSDUDWLRQ7KXVE\XVLQJELRDGKHVLYH PROHFXOHVLWLVSRVVLEOHWRUHWDLQWKHSUHSDUDWLRQDWWKH DFWLRQVLWHDQGWRGLUHFWWKHGUXJWRDVSHFLFVLWHRUWLVVXH 2WKHUIHDWXUHVDVVRFLDWHGZLWKWKHGHYHORSPHQWRIFRQWURO OHGGUXJGHOLYHU\V\VWHPVXVLQJELRDGKHVLYHPROHFXOHV LQFOXGHDGHFUHDVHLQGUXJDGPLQLVWUDWLRQIUHTXHQF\DQG DQLQFUHDVHLQSDWLHQWFRPSOLDQFHWRWKHWKHUDS\:RRGOH\ 7KHUHIRUHDELRDGKHVLYHV\VWHPFRQWUROOLQJGUXJ UHOHDVHFRXOGLPSURYHWKHWUHDWPHQWRIGLVHDVHVKHOSLQJ WRPDLQWDLQDQHIIHFWLYHFRQFHQWUDWLRQRIWKHGUXJDWWKH DFWLRQVLWH+XDQJ HWDO 0XFRXVPHPEUDQHLVWKHPDLQDGPLQLVWUDWLRQVLWHIRU ELRDGKHVLYHV\VWHPVDOWKRXJKWKHQHHGIRUQHZELRDGKH VLYHIRUPXODWLRQVIRUGHUPDODGPLQLVWUDWLRQKDVDOVREHHQ UHSRUWHGZKHQSURORQJHGFXWDQHRXVDFWLRQLVGHVLUHG$ SURORQJHGHIIHFWXSRQWKHGHUPDODGPLQLVWUDWLRQRIFUHDPV VROXWLRQVDQGORWLRQVLVXQH[SHFWHGVLQFHVXFKSUHSDUDWLRQV FDQEHHDVLO\UHPRYHGIURPWKHVNLQE\PRLVWXUHWHPSHUD WXUHDQGSK\VLFDOPRYHPHQWV6KLQ HWDO 0XFRXVOPHPEUDQHVRIKXPDQRUJDQLVPDUHUHODWL YHO\SHUPHDEOHDQGDOORZIDVWGUXJDEVRUSWLRQ-DVWL/L &OHDU\7KH\DUHFKDUDFWHUL]HGE\DQHSLWKHOLDOOD\HU ZKRVHVXUIDFHLVFRYHUHGE\PXFXV7KHPXFXVFRQWDLQV JO\FRSURWHLQVOLSLGVLQRUJDQLFVDOWVDQGZDWHUE\ PDVVPDNLQJLWDKLJKO\K\GUDWHGV\VWHP0XFLQLVWKH PRVWLPSRUWDQWJO\FRSURWHLQRIPXFXVDQGLVUHVSRQVLEOH IRULWVVWUXFWXUH7KHPDLQIXQFWLRQVRIPXFXVDUHSURWHF WLQJDQGOXEULFDWLQJWKHHSLWKHOLXPDQGRWKHUDGGLWLRQDO IXQFWLRQVGHSHQGLQJRQWKHHSLWKHOLXPFRYHUHG0XFXV WKLFNQHVVFDQYDU\IURPPLQWKHVWRPDFKWROHVV WKDQPLQWKHRUDOFDYLW\6PDUW7KHPXFRXV VLWHPRVWXVHGIRUGUXJDGPLQLVWUDWLRQDQGDEVRUSWLRQLV JDVWURLQWHVWLQDO-XQJLQJHU7KDQRX9HUKRHIEXW RWKHUURXWHVLQFOXGLQJQDVDORFXODUEXFFDOYDJLQDOUHF WDORUDODQGSHULRGRQWDOKDYHDOVREHHQVWXGLHG%UXVFKL HWDO %UXVFKL+lJHUVWU|P:RRGOH\ %LRDGKHVLYHV\VWHPVDSSOLHGWRPXFRXVPHPEUDQH DUHIUHTXHQWO\GHQHGDVPXFRDGKHVLYHEXWWKHWHUPVDUH LQWHUFKDQJHDEOH /HXQJ5RELQVRQ ,WLVIHDVLEOHWR GHVLJQDELRPXFRDGKHVLYHV\VWHPLQGLIIHUHQWGRVDJHIRU PVVLQFHWKHSURSHUWLHVRIDGKHVLRQODUJHO\GHSHQGRQWKH IHDWXUHVRIWKHPDWHULDOXVHGLQLWVSUHSDUDWLRQ(YDQJHOLVWD 7KHUHIRUHVHYHUDOFRQYHQWLRQDOGUXJGHOLYHU\V\V WHPVDOUHDG\LQXVHFDQEHFRPHELRDGKHVLYHDIWHUUHGHVLJQ E\LQFOXGLQJELRDGKHVLYHVXEVWDQFHVLQWKHLUIRUPXODWLRQ 7KLVDSSURDFKWRFRQIHU%LRDGKHVLRQSURSHUWLHVKDVEHHQ ZLGHO\DSSOLHGLQWKHGHYHORSPHQWRIDQXPEHURIGUXJGH OLYHU\V\VWHPV6ROLGPLFURDQGQDQRSDUWLFXODWHV\VWHPV EDVHGRQFKLWRVDQDQGGHULYDWLYHVKDYHEHHQWKHIRFXVRI VHYHUDOVWXGLHV%UDYR2VXQD HWDO :LWWD\D$UHHNXO .UXHQDWH3UDKVDUQPLFURHPXOVLRQVDUHWKHUPR G\QDPLFDOO\VWDEOHDQGLVRWURSLFOLTXLGV\VWHPVZKLFK DOORZWKHLQFRUSRUDWLRQRIELRDGKHVLYHPROHFXOHVVXFKDV SRO\FDUERSKLO9\DV HWDO FROORLGDOGLVSHUVLRQVRI ELRDGKHVLYHSRO\PHUVIUHTXHQWO\XVHGLQSUHSDUDWLRQVIRU RUDOK\JLHQH.RFNLVFK HWDO VHPLVROLGV\VWHPV DVOLTXLGFU\VWDOOLQHPHVRSKDVHV%UXVFKL HWDO DQGK\GURJHOV%UXVFKL HWDO +XDQJ HWDO ZKLFKFDQLQFUHDVHWKHFRQWDFWWLPHEHWZHHQSUH SDUDWLRQDQGPXFRXVPHPEUDQHDIWHUWKH\XQGHUJR LQVLWX JHODWLRQ 7KHUHDUHDQXPEHURIPDWHULDOVXVHGIRUGHYHORSLQJ VXFKV\VWHPV7KHPRVWVWXGLHGPDWHULDOVDUHWKHSRO\PHUV GHULYHGIURPSRO\DFU\OLFDFLGVXFKDVSRO\FDUERSKLO DQGFDUERPHUVSRO\PHUVGHULYHGIURPFHOOXORVHVXFK DVK\GUR[\HWK\OFHOOXORVHDQGFDUER[\PHWK\OFHOOXORVH DOJLQDWHVFKLWRVDQDQGGHULYDWLYHVDQGPRUHUHFHQWO\ OHFWLQVDQGWKHLUGHULYDWLYHV*UDERYDF*XJJL%HUQNRS 6FKQUFK6PDUW $OWKRXJKVWXGLHVRQWKHPHFKDQLVPVLQYROYHGLQ PXFRDGKHVLRQDQGWKHGHYHORSPHQWRIQRYHOPXFRDGKHVL YHV\VWHPVDQGSRO\PHUVKDYHHYROYHGRYHUWKHODVWWZHQW\ \HDUVPXFRDGKHVLRQLVQRW\HWIXOO\XQGHUVWRRG4XDQWLWD WLYHDQGTXDOLWDWLYHWHFKQLTXHVDUHVWLOOWUHDWHGVHSDUDWHO\ 7KHDLPRIWKLVVWXG\ZDVWRV\VWHPDWLFDOO\UHYLHZWKH PHFKDQLVPVDQGWKHRULHVLQYROYLQJPXFRDGKHVLRQDV ZHOODVWRGHVFULEHWKHPHWKRGVDQGSRO\PHUVPRVWXVHG LQPXFRDGKHVLYHV\VWHPVIRUGUXJGHOLYHU\ MECHANISMS OF MUCOADHESION 7KHPHFKDQLVPRIDGKHVLRQRIFHUWDLQPDFUR PROHFXOHVWRWKHVXUIDFHRIDPXFRXVWLVVXHLVQRWZHOO XQGHUVWRRG\HW7KHPXFRDGKHVLYHPXVWVSUHDGRYHUWKH VXEVWUDWHWRLQLWLDWHFORVHFRQWDFWDQGLQFUHDVHVXUIDFH FRQWDFWSURPRWLQJWKHGLIIXVLRQRILWVFKDLQVZLWKLQWKH PXFXV$WWUDFWLRQDQGUHSXOVLRQIRUFHVDULVHDQGIRUD PXFRDGKHVLYHWREHVXFFHVVIXOWKHDWWUDFWLRQIRUFHVPXVW GRPLQDWH(DFKVWHSFDQEHIDFLOLWDWHGE\WKHQDWXUHRIWKH GRVDJHIRUPDQGKRZLWLVDGPLQLVWHUHG)RUH[DPSOHD SDUWLDOO\K\GUDWHGSRO\PHUFDQEHDGVRUEHGE\WKHVXEV WUDWHEHFDXVHRIWKHDWWUDFWLRQE\WKHVXUIDFHZDWHU/HH 3DUN5RELQVRQ HWDO 7KXVWKHPHFKDQLVPRIPXFRDGKHVLRQLVJHQHUDOO\ GLYLGHGLQWZRVWHSVWKHFRQWDFWVWDJHDQGWKHFRQVROLGD WLRQVWDJH)LJXUH7KHUVWVWDJHLVFKDUDFWHUL]HGE\
Page 3
0XFRDGKHVLYHGUXJGHOLYHU\V\VWHPV WKHFRQWDFWEHWZHHQWKHPXFRDGKHVLYHDQGWKHPXFRXV PHPEUDQHZLWKVSUHDGLQJDQGVZHOOLQJRIWKHIRUPX ODWLRQLQLWLDWLQJLWVGHHSFRQWDFWZLWKWKHPXFXVOD\HU +lJHUVWURP,QVRPHFDVHVVXFKDVIRURFXODURU YDJLQDOIRUPXODWLRQVWKHGHOLYHU\V\VWHPLVPHFKDQLFDOO\ DWWDFKHGRYHUWKHPHPEUDQH,QRWKHUFDVHVWKHGHSRVLWLRQ LVSURPRWHGE\WKHDHURG\QDPLFVRIWKHRUJDQWRZKLFKWKH V\VWHPLVDGPLQLVWHUHGVXFKDVIRUWKHQDVDOURXWH2QWKH RWKHUKDQGLQWKHJDVWURLQWHVWLQDOWUDFWGLUHFWIRUPXODWLRQ DWWDFKPHQWRYHUWKHPXFRXVPHPEUDQHLVQRWIHDVLEOH 3HULVWDOWLFPRWLRQVFDQFRQWULEXWHWRWKLVFRQWDFWEXWWKH UHLVOLWWOHHYLGHQFHLQWKHOLWHUDWXUHVKRZLQJDSSURSULDWH DGKHVLRQ$GGLWLRQDOO\DQXQGHVLUDEOHDGKHVLRQLQWKH HVRSKDJXVFDQRFFXU,QWKHVHFDVHVPXFRDGKHVLRQFDQ EHH[SODLQHGE\SHULVWDOVLVWKHPRWLRQRIRUJDQLFXLGV LQWKHRUJDQFDYLW\RUE\%URZQLDQPRWLRQ,IWKHSDUWLFOH DSSURDFKHVWKHPXFRXVVXUIDFHLWZLOOFRPHLQWRFRQWDFW ZLWKUHSXOVLYHIRUFHVRVPRWLFSUHVVXUHHOHFWURVWDWLFUH SXOVLRQHWFDQGDWWUDFWLYHIRUFHVYDQGHU:DDOVIRUFHV DQGHOHFWURVWDWLFDWWUDFWLRQ7KHUHIRUHWKHSDUWLFOHPXVW RYHUFRPHWKLVUHSXOVLYHEDUULHU6PDUW ,QWKHFRQVROLGDWLRQVWHS)LJXUHWKHPXFRDGKH VLYHPDWHULDOVDUHDFWLYDWHGE\WKHSUHVHQFHRIPRLVWXUH 0RLVWXUHSODVWLFL]HVWKHV\VWHPDOORZLQJWKHPXFRDGKH VLYHPROHFXOHVWREUHDNIUHHDQGWROLQNXSE\ZHDNYDQ GHU:DDOVDQGK\GURJHQERQGV6PDUW(VVHQWLDOO\ WKHUHDUHWZRWKHRULHVH[SODLQLQJWKHFRQVROLGDWLRQVWHS WKHGLIIXVLRQWKHRU\DQGWKHGHK\GUDWLRQWKHRU\$FFRUGLQJ WRGLIIXVLRQWKHRU\WKHPXFRDGKHVLYHPROHFXOHVDQGWKH JO\FRSURWHLQVRIWKHPXFXVPXWXDOO\LQWHUDFWE\PHDQV RILQWHUSHQHWUDWLRQRIWKHLUFKDLQVDQGWKHEXLOGLQJRI VHFRQGDU\ERQGV6PDUW)RUWKLVWRWDNHSODFHWKH PXFRDGKHVLYHGHYLFHKDVIHDWXUHVIDYRULQJERWKFKHPLFDO DQGPHFKDQLFDOLQWHUDFWLRQV)RUH[DPSOHPROHFXOHVZLWK K\GURJHQERQGVEXLOGLQJJURXSV2+&22+ZLWKDQ DQLRQLFVXUIDFHFKDUJHKLJKPROHFXODUZHLJKWH[LEOH FKDLQVDQGVXUIDFHDFWLYHSURSHUWLHVZKLFKLQGXFWLWVVSUH DGWKURXJKRXWWKHPXFXVOD\HUFDQSUHVHQWPXFRDGKHVLYH SURSHUWLHV0DWKLRZLW]&KLFNHULQJ/HKU $FFRUGLQJWRGHK\GUDWLRQWKHRU\PDWHULDOVWKDWDUH DEOHWRUHDGLO\JHOLI\LQDQDTXHRXVHQYLURQPHQWZKHQ SODFHGLQFRQWDFWZLWKWKHPXFXVFDQFDXVHLWVGHK\GUDWLRQ GXHWRWKHGLIIHUHQFHRIRVPRWLFSUHVVXUH7KHGLIIHUHQFH LQFRQFHQWUDWLRQJUDGLHQWGUDZVWKHZDWHULQWRWKHIRUPX ODWLRQXQWLOWKHRVPRWLFEDODQFHLVUHDFKHG7KLVSURFHVV OHDGVWRWKHPL[WXUHRIIRUPXODWLRQDQGPXFXVDQGFDQ WKXVLQFUHDVHFRQWDFWWLPHZLWKWKHPXFRXVPHPEUDQH 7KHUHIRUHLWLVWKHZDWHUPRWLRQWKDWOHDGVWRWKHFRQVROL GDWLRQRIWKHDGKHVLYHERQGDQGQRWWKHLQWHUSHQHWUDWLRQRI PDFURPROHFXODUFKDLQV+RZHYHUWKHGHK\GUDWLRQWKHRU\ LVQRWDSSOLFDEOHIRUVROLGIRUPXODWLRQVRUKLJKO\K\GUDWHG IRUPV6PDUW MUCOADHESION THEORIES $OWKRXJKWKHFKHPLFDODQGSK\VLFDOEDVLVRIPXFR DGKHVLRQDUHQRW\HWZHOOXQGHUVWRRGWKHUHDUHVL[FODVVL FDOWKHRULHVDGDSWHGIURPVWXGLHVRQWKHSHUIRUPDQFHRI VHYHUDOPDWHULDOVDQGSRO\PHUSRO\PHUDGKHVLRQZKLFK H[SODLQWKHSKHQRPHQRQ+lJHUVWU|P+XDQJ HW DO 6PDUW Electronic theory (OHFWURQLFWKHRU\LVEDVHGRQWKHSUHPLVHWKDWERWK PXFRDGKHVLYHDQGELRORJLFDOPDWHULDOVSRVVHVVRSSRVLQJ HOHFWULFDOFKDUJHV7KXVZKHQERWKPDWHULDOVFRPHLQWR FRQWDFWWKH\WUDQVIHUHOHFWURQVOHDGLQJWRWKHEXLOGLQJRID GRXEOHHOHFWURQLFOD\HUDWWKHLQWHUIDFHZKHUHWKHDWWUDFWLYH IRUFHVZLWKLQWKLVHOHFWURQLFGRXEOHOD\HUGHWHUPLQHVWKH PXFRDGKHVLYHVWUHQJWK0DWKLRZLW]&KLFNHULQJ/HKU Adsorption theory $FFRUGLQJWRWKHDGVRUSWLRQWKHRU\WKHPXFRDGKH VLYHGHYLFHDGKHUHVWRWKHPXFXVE\VHFRQGDU\FKHPLFDO LQWHUDFWLRQVVXFKDVLQYDQGHU:DDOVDQGK\GURJHQERQGV HOHFWURVWDWLFDWWUDFWLRQRUK\GURSKRELFLQWHUDFWLRQV)RU H[DPSOHK\GURJHQERQGVDUHWKHSUHYDOHQWLQWHUIDFLDOIRU FIGURE 1 7KHWZRVWHSVRIWKHPXFRDGKHVLRQSURFHVV FIGURE 2 'HK\GUDWLRQWKHRU\RIPXFRDGKHVLRQ
Page 4
)&&DUYDOKR0/%UXVFKL5&(YDQJHOLVWD03'*UHPLmR FHVLQSRO\PHUVFRQWDLQLQJFDUER[\OJURXSV+lJHUVWU|P +XDQJ HWDO /HH3DUN5RELQVRQ 6PDUW6XFKIRUFHVKDYHEHHQFRQVLGHUHGWKHPRVW LPSRUWDQWLQWKHDGKHVLYHLQWHUDFWLRQSKHQRPHQRQ6PDUW EHFDXVHDOWKRXJKWKH\DUHLQGLYLGXDOO\ZHDND JUHDWQXPEHURILQWHUDFWLRQVFDQUHVXOWLQDQLQWHQVHJOREDO DGKHVLRQ0DWKLRZLW]&KLFNHULQJ/HKU Wetting theory 7KHZHWWLQJWKHRU\DSSOLHVWROLTXLGV\VWHPVZKLFK SUHVHQWDIQLW\WRWKHVXUIDFHLQRUGHUWRVSUHDGRYHULW 7KLVDIQLW\FDQEHIRXQGE\XVLQJPHDVXULQJWHFKQLTXHV VXFKDVWKHFRQWDFWDQJOH7KHJHQHUDOUXOHVWDWHVWKDWWKH ORZHUWKHFRQWDFWDQJOHWKHQWKHJUHDWHUWKHDIQLW\)LJXUH 7KHFRQWDFWDQJOHVKRXOGEHHTXDORUFORVHWR]HURWR SURYLGHDGHTXDWHVSUHDGDELOLW\0DWKLRZLW]&KLFNHULQJ /HKU 7KHVSUHDGDELOLW\FRHIFLHQW $% FDQEHFDOFXODWHG IURPWKHGLIIHUHQFHEHWZHHQWKHVXUIDFHHQHUJLHV DQG DQGWKHLQWHUIDFLDOHQHUJ\ $% DVLQGLFDWHGLQHTXDWLRQ 6PDUW 7KHJUHDWHUWKHLQGLYLGXDOVXUIDFHHQHUJ\RIPXFXV DQGGHYLFHLQUHODWLRQWRWKHLQWHUIDFLDOHQHUJ\WKHJUHDWHU WKHDGKHVLRQZRUN LHWKHJUHDWHUWKHHQHUJ\QHHGHG WRVHSDUDWHWKHWZRSKDVHV6PDUW Diffusion theory 'LIIXVLRQWKHRU\GHVFULEHVWKHLQWHUSHQHWUDWLRQRI ERWKSRO\PHUDQGPXFLQFKDLQVWRDVXIFLHQWGHSWKWR FUHDWHDVHPLSHUPDQHQWDGKHVLYHERQG)LJXUH,WLV EHOLHYHGWKDWWKHDGKHVLRQIRUFHLQFUHDVHVZLWKWKHGH JUHHRISHQHWUDWLRQRIWKHSRO\PHUFKDLQV0DWKLRZLW] &KLFNHULQJ/HKU7KLVSHQHWUDWLRQUDWHGHSHQGV RQWKHGLIIXVLRQFRHIFLHQWH[LELOLW\DQGQDWXUHRIWKH PXFRDGKHVLYHFKDLQVPRELOLW\DQGFRQWDFWWLPH+lJHUV WU|P+XDQJ HWDO /HH3DUN5RELQVRQ 6PDUW$FFRUGLQJWRWKHOLWHUDWXUHWKHGHSWKRILQ WHUSHQHWUDWLRQUHTXLUHGWRSURGXFHDQHIFLHQWELRDGKHVLYH ERQGOLHVLQWKHUDQJHP7KLVLQWHUSHQHWUDWLRQ GHSWKRISRO\PHUDQGPXFLQFKDLQVFDQEHHVWLPDWHGE\ HTXDWLRQ ZKHUH W LVWKHFRQWDFWWLPHDQG LVWKHGLIIXVLRQFRH IFLHQWRIWKHPXFRDGKHVLYHPDWHULDOLQWKHPXFXV7KH DGKHVLRQVWUHQJWKIRUDSRO\PHULVUHDFKHGZKHQWKHGHSWK RISHQHWUDWLRQLVDSSUR[LPDWHO\HTXLYDOHQWWRWKHSRO\PHU FKDLQVL]H0DWKLRZLW]&KLFNHULQJ/HKU ,QRUGHUIRUGLIIXVLRQWRRFFXULWLVLPSRUWDQWWKDW WKHFRPSRQHQWVLQYROYHGKDYHJRRGPXWXDOVROXELOLW\ WKDWLVERWKWKHELRDGKHVLYHDQGWKHPXFXVKDYHVLPLODU FKHPLFDOVWUXFWXUHV7KHJUHDWHUWKHVWUXFWXUDOVLPLODULW\ WKHEHWWHUWKHPXFRDGKHVLYHERQG0DWKLRZLW]&KLFNHULQJ /HKU Fracture theory 7KLVLVSHUKDSVWKHPRVWXVHGWKHRU\LQVWXGLHVRQ WKHPHFKDQLFDOPHDVXUHPHQWRIPXFRDGKHVLRQ0DWKLR ZLW]&KLFNHULQJ/HKU,WDQDO\VHVWKHIRUFHUHTXLUHG WRVHSDUDWHWZRVXUIDFHVDIWHUDGKHVLRQLVHVWDEOLVKHG+l JHUVWU|P6PDUW7KLVIRUFH LVIUHTXHQWO\ FDOFXODWHGLQWHVWVRIUHVLVWDQFHWRUXSWXUHE\WKHUDWLRRI WKHPD[LPDOGHWDFKPHQWIRUFH DQGWKHWRWDOVXUIDFH DUHD LQYROYHGLQWKHDGKHVLYHLQWHUDFWLRQHTXDWLRQ FIGURE 3 6FKHPDWLFGLDJUDPVKRZLQJLQXHQFHRIFRQWDFW DQJOHEHWZHHQGHYLFHDQGPXFRXVPHPEUDQHRQELRDGKHVLRQ FIGURE 4 6HFRQGDU\LQWHUDFWLRQVUHVXOWLQJIURPLQWHUGLIIXVLRQ RISRO\PHUFKDLQVRIELRDGKHVLYHGHYLFHDQGRIPXFXV
Page 5
0XFRDGKHVLYHGUXJGHOLYHU\V\VWHPV ,QDVLQJOHFRPSRQHQWXQLIRUPV\VWHPWKHIUDFWXUH IRUFH ZKLFKLVHTXLYDOHQWWRWKHPD[LPDOUXSWXUHWHQVLOH VWUHQJWK LVSURSRUWLRQDOWRWKHIUDFWXUHHQHUJ\ IRU DQGWRWKHFULWLFDOEUHDNLQJOHQJWK IRUWKHIUDFWXUHVLWHDVGHVFULEHGLQHTXDWLRQ )UDFWXUHHQHUJ\ FDQEHREWDLQHGIURPWKHUHYHU VLEOHDGKHVLRQZRUN HQHUJ\UHTXLUHGWRSURGXFHQHZ IUDFWXUHGVXUIDFHVDQGWKHLUUHYHUVLEOHDGKHVLRQZRUN ZRUNRISODVWLFGHIRUPDWLRQSURYRNHGE\WKHUHPRYDORI DSURRIWLSXQWLOWKHGLVUXSWLRQRIWKHDGKHVLYHERQGDQG ERWKYDOXHVDUHH[SUHVVHGDVXQLWVRIIUDFWXUHVXUIDFH 7KHHODVWLFPRGXOHRIWKHV\VWHP LVUHODWHGWRWKH VWUHVV DQGWRWKHVKHDU E\+RRNHVODZ ,QHTXDWLRQWKHVWUHVVLVWKHUDWLREHWZHHQIRUFH DQGDUHD DQGVKHDULVJLYHQE\WKHUDWLREHWZHHQ WKHYDULDWLRQRIV\VWHPWKLFNQHVV DQGWKHRULJLQDO WKLFNQHVV $FULWLFLVPRIWKLVDQDO\VLVLVWKDWWKHV\VWHPXQGHU LQYHVWLJDWLRQPXVWKDYHNQRZQSK\VLFDOGLPHQVLRQVDQG VKRXOGEHFRQVWLWXWHGE\DVLQJOHDQGXQLIRUPPDWHULDO,Q YLUWXHRIWKLVWKHUHODWLRQVKLSREWDLQHGFDQQRWEHDSSOLHG WRDQDO\]HWKHIUDFWXUHVLWHRIDPXOWLSOHFRPSRQHQWELRD GKHVLYH,QWKLVFDVHWKHHTXDWLRQVKRXOGEHH[SDQGHGWR DFFRPPRGDWHHODVWLFGLPHQVLRQVDQGPRGXOHVIRUHDFK FRPSRQHQW%HVLGHVLWPXVWEHFRQVLGHUHGWKDWDIDLOXUHRI DGKHVLRQZLOORFFXUDWWKHELRDGKHVLYHLQWHUIDFH+RZHYHU LWKDVEHHQGHPRQVWUDWHGWKDWWKHUXSWXUHUDUHO\RFFXUV DWWKHVXUIDFHEXWQHDULW0DWKLRZLW]&KLFNHULQJ/HKU RUDWWKHZHDNHVWSRLQWZKLFKFDQEHWKHLQWHUIDFH LWVHOIWKHPXFXVOD\HURUWKHK\GUDWHGUHJLRQRIWKHPXFXV DVLOOXVWUDWHGLQ)LJXUH6PDUW 6LQFHWKHIUDFWXUHWKHRU\LVFRQFHUQHGRQO\ZLWKWKH IRUFHUHTXLUHGWRVHSDUDWHWKHSDUWVLWGRHVQRWWDNHLQWRDF FIGURE 5 5HJLRQVZKHUHWKHPXFRDGKHVLYHERQGUXSWXUH FDQRFFXU FRXQWWKHLQWHUSHQHWUDWLRQRUGLIIXVLRQRISRO\PHUFKDLQV &RQVHTXHQWO\LWLVDSSURSULDWHIRUXVHLQWKHFDOFXODWLRQV IRUULJLGRUVHPLULJLGELRDGKHVLYHPDWHULDOVLQZKLFK WKHSRO\PHUFKDLQVGRQRWSHQHWUDWHLQWRWKHPXFXVOD\HU 0DWKLRZLW]&KLFNHULQJ/HKU Mechanical theory 0HFKDQLFDOWKHRU\FRQVLGHUVDGKHVLRQWREHGXH WRWKHOOLQJRIWKHLUUHJXODULWLHVRQDURXJKVXUIDFHE\D PXFRDGKHVLYHOLTXLG0RUHRYHUVXFKURXJKQHVVLQFUHD VHVWKHLQWHUIDFLDODUHDDYDLODEOHWRLQWHUDFWLRQVWKHUHE\ DLGLQJGLVVLSDWLQJHQHUJ\DQGFDQEHFRQVLGHUHGWKHPRVW LPSRUWDQWSKHQRPHQRQRIWKHSURFHVV3HSSDV6DKOLQ 6PDUW ,WLVXQOLNHO\WKDWWKHPXFRDGKHVLRQSURFHVVLVWKH VDPHIRUDOOFDVHVDQGWKHUHIRUHLWFDQQRWEHGHVFULEHGE\ DVLQJOHWKHRU\,QIDFWDOOWKHRULHVDUHUHOHYDQWWRLGHQWLI\ WKHLPSRUWDQWSURFHVVYDULDEOHV/HH3DUN5RELQVRQ 7KHPHFKDQLVPVJRYHUQLQJPXFRDGKHVLRQDUHDOVR GHWHUPLQHGE\WKHLQWULQVLFSURSHUWLHVRIWKHIRUPXODWLRQ DQGE\WKHHQYLURQPHQWLQZKLFKLWLVDSSOLHG /HH3DUN 5RELQVRQ,QWULQVLFIDFWRUVRIWKHSRO\PHUDUHUHODWHG WRLWVPROHFXODUZHLJKWFRQFHQWUDWLRQDQGFKDLQH[LELOLW\ )RUOLQHDUSRO\PHUVPXFRDGKHVLRQLQFUHDVHVZLWKPROHFX ODUZHLJKWEXWWKHVDPHUHODWLRQVKLSGRHVQRWKROGIRUQRQ OLQHDUSRO\PHUV,WKDVEHHQVKRZQWKDWPRUHFRQFHQWUDWHG PXFRDGKHVLYHGLVSHUVLRQVDUHUHWDLQHGRQWKHPXFRXVPHP EUDQHIRUORQJHUSHULRGVDVLQWKHFDVHRIV\VWHPVIRUPHGE\ LQVLWX JHOLFDWLRQ$IWHUDSSOLFDWLRQVXFKV\VWHPVVSUHDG HDVLO\VLQFHWKH\SUHVHQWUKHRORJLFDOSURSHUWLHVRIDOLTXLG EXWJHOLI\DVWKH\FRPHLQWRFRQWDFWWKHDEVRUSWLRQVLWHWKXV SUHYHQWLQJWKHLUUDSLGUHPRYDO&KDLQH[LELOLW\LVFULWLFDO WRFRQVROLGDWHWKHLQWHUSHQHWUDWLRQEHWZHHQIRUPXODWLRQDQG PXFXV/HH3DUN5RELQVRQ (QYLURQPHQWUHODWHGIDFWRUVLQFOXGHS+LQLWLDO FRQWDFWWLPHVZHOOLQJDQGSK\VLRORJLFDOYDULDWLRQV7KH S+FDQLQIOXHQFHWKHIRUPDWLRQRILRQL]DEOHJURXSVLQ SRO\PHUVDVZHOODVWKHIRUPDWLRQRIFKDUJHVRQWKHPXFXV
Page 6
)&&DUYDOKR0/%UXVFKL5&(YDQJHOLVWD03'*UHPLmR VXUIDFH&RQWDFWWLPHEHWZHHQPXFRDGKHVLYHDQGPXFXV OD\HUGHWHUPLQHVWKHH[WHQWRIFKDLQLQWHUSHQHWUDWLRQ 6XSHUK\GUDWLRQRIWKHV\VWHPFDQOHDGWREXLOGXSRI PXFLODJHZLWKRXWDGKHVLRQ7KHWKLFNQHVVRIWKHPXFXV OD\HUFDQYDU\IURPWR PLQWKHVWRPDFK6PDUW WROHVVWKDQPLQWKHRUDOFDYLW\2WKHUSK\VLROR JLFDOYDULDWLRQVFDQDOVRRFFXUZLWKGLVHDVHV/HH3DUN 5RELQVRQ 1RQHRIWKHVHPHFKDQLVPVRUWKHRULHVDORQHFDQ H[SODLQWKHPXFRDGKHVLRQZKLFKRFFXUVLQDQDUUD\RI GLIIHUHQWVLWXDWLRQV+RZHYHUWKHXQGHUVWDQGLQJRIWKHVH PHFKDQLVPVLQHDFKLQVWDQFHFDQKHOSWRZDUGWKHGHYH ORSPHQWRIQHZPXFRDGKHVLYHSURGXFWV6PDUW MUCOADHESIVE MATERIALS 7KHUVWVWXG\SUHVHQWLQJWKHXVHRIDPXFRDGKHVLYH PDWHULDOZDVFRQGXFWHGE\1DJDLDQGSURSRVHGDQLP SURYHGWUHDWPHQWIRUVWRPDWLWLVE\XVLQJDGKHVLYHWDEOHWV $GGLWLRQDOO\DQLQFUHDVHLQWKHV\VWHPLFELRDYDLODELOLW\ RILQVXOLQZDVREVHUYHGLQWKHIRUPRIELRDGKHVLYHSRZ GHUDIWHUQDVDODGPLQLVWUDWLRQLQGRJV1DJDL HWDO 1DJDL7KHUHDIWHUELRDGKHVLYHPDWHULDOVKDYHEHHQ XVHGDVDEVRUSWLRQSURPRWHUVIRUVHYHUDODGPLQLVWUDWLRQ URXWHV(DUOLHUH[SHULPHQWVZHUHDOVRGRQHZLWKNQRZQ SRO\PHUVDYDLODEOHRQWKHPDUNHWVXFKDVSRO\DFU\OLF DFLGV&XUUHQWO\WKHODWHVWUHVHDUFKLVVHHNLQJWRGHYHORS PDWHULDOVWKDWGLUHFWWKHIRUPXODWLRQPRUHVSHFLFDOO\WR WKHDFWLRQVLWHDQGWKDWFDQRIIHURWKHUIXQFWLRQVEHVLGHV PXFRDGKHVLRQVXFKDVFRQWURORYHUSHUPHDWLRQZLWKLQ HSLWKHOLDOWLVVXHVDQGLQDFWLYDWLRQRIHQ]\PHVZKLFKFDQ FRPSURPLVHUHOHDVHV\VWHPDFWLRQ+lJHUVWU|P First generation mucoadhesive materials 7KHVHPDWHULDOVDUHQDWXUDORUV\QWKHWLFK\GURSKLOLF PROHFXOHVFRQWDLQLQJQXPHURXVRUJDQLFIXQFWLRQVWKDW JHQHUDWHK\GURJHQERQGVVXFKDVFDUER[\OK\GUR[\O DQGDPLQRJURXSVZKLFKGRQRWDGKHUHVSHFLFDOO\RQWR VHYHUDOVXUIDFHV7KHYHU\UVWXVHRIPXFRDGKHVLYHZDV DVGHQWXUH[HUVDQGWKHPRVWNQRZQH[DPSOHVDUHFDU ERPHUVFKLWRVDQVDOJLQDWHVDQGFHOOXORVHGHULYDWLYHV 7KH\FDQEHLQFRUSRUDWHGLQWRVROLGIRUPXODWLRQVVXFK DVWDEOHWVWUDQVGHUPDODGKHVLYHVDQGPLFURSDUWLFOHVDQG LQWRVHPLVROLGIRUPXODWLRQVLQFOXGLQJJHOVRLQWPHQWV SDVWHVDQGVXSSRVLWRULHV6PDUW7KHVHSRO\PHUV FDQEHVXEGLYLGHGLQWRWKUHHFODVVHVFDWLRQLFDQLRQLFDQG QRQLRQLF &DWLRQLFPROHFXOHVFDQLQWHUDFWZLWKWKHPXFXV VXUIDFHVLQFHLWLVQHJDWLYHO\FKDUJHGDWSK\VLRORJLFDO S+0XFRDGKHVLRQRIFDWLRQLFSRO\PHUVVXFKDVFKLWRVDQ RFFXUVEHFDXVHRIWKHHOHFWURVWDWLFLQWHUDFWLRQVRIWKHLU DPLQRJURXSVZLWKWKHVLDOLFJURXSVRIPXFLQLQWKHPX FXVOD\HU&KLWRVDQLVDVHPLV\QWKHWLFSRO\PHUREWDLQHG E\WKHGHDFHW\ODWLRQRIFKLWLQDQGKDVEHHQH[WHQVLYHO\ LQYHVWLJDWHGDVDGUXJGHOLYHU\PXFRDGKHVLYHV\VWHPV :RRGOH\6WXGLHVKDYHGHPRQVWUDWHGWKDWFKLWRVDQ FDQSURPRWHWKHDEVRUSWLRQRIK\GURSKLOLFPROHFXOHVE\ WKHVWUXFWXUDOUHRUJDQL]DWLRQRIWKHSURWHLQVDVVRFLDWHGWR WKHLQWHUFHOOXODUMXQFWLRQV%UDYR2VXQD HWDO 7KH SUHVHQFHRIFKLWRVDQDWWKHVXUIDFHRIQDQRSDUWLFOHVFOHDUO\ LQFUHDVHGWKHLULQWHVWLQDOPXFRDGKHVLYHEHKDYLRULQUDWV %UDYR2VXQD HWDO %RFDWDM HWDO GHPRQV WUDWHGLQWKHLUVWXGLHVWKDWFKLWRVDQVKRZHGKLJKHUPXFRD GKHVLRQWKDQFDUER[\PHWK\OFHOOXORVHDQGSRO\FDUERSKLO ,QFRQWUDVWV\QWKHWLFSRO\PHUVGHULYHGIURPSRO\D FU\OLFDFLGFDUERPHUVDUHQHJDWLYHO\FKDUJHGEXWDUH DOVRPXFRDGKHVLYH,QWKLVFDVHPXFRDGKHVLRQUHVXOWV IURPSK\VLFDOFKHPLFDOSURFHVVHVVXFKDVK\GURSKRELF LQWHUDFWLRQVK\GURJHQDQGYDQGHU:DDOVERQGVZKLFKDUH FRQWUROOHGE\S+DQGLRQLFFRPSRVLWLRQ:RRGOH\ 3RO\DFU\OLFDFLGK\GURJHOVKDYHEHHQH[WHQVLYHO\VWXGLHG DVPXFRDGKHVLYHV\VWHPV7KHLUFKDLQVDUHH[LEOHDQG KDYHQRQDEUDVLYHFKDUDFWHULVWLFVZKHQLQWKHSDUWLDOO\ K\GUDWHGVWDWHZKLFKGHFUHDVHVWKHWLVVXHGDPDJHFDXVHG E\IULFWLRQZKHQWKH\FRPHLQWRFRQWDFW+XDQJ HWDO 7KHPDMRULW\RISRO\DFU\OLFDFLGGHULYDWLYHVDUH QRWZDWHUVROXEOHVXFKDVSRO\FDUERSKLOEXWIRUPYLVFRXV JHOVZKHQK\GUDWHG:RRGOH\2WKHUH[DPSOHVRI DQLRQLFSRO\PHUVDUHFDUER[\PHWK\OFHOOXORVHDQGDOJL QDWHV7KHDOJLQDWHVQHJDWLYHO\FKDUJHGSRO\VDFFKDULGHV DUHZLGHO\XVHGLQWKHSURGXFWLRQRIPLFURSDUWLFOHVDQG DUHIUHTXHQWO\UHSRUWHGDVSRO\DQLRQLFPXFRDGKHVLYH SRO\PHUV :LWWD\D$UHHNXO.UXHQDWH3UDKVDUQ 1RQLRQLFSRO\PHUVLQFOXGLQJK\GUR[\SURS\OPH WK\OFHOOXORVHK\GUR[\HWK\OFHOOXORVHDQGPHWK\OFHOOXORVH SUHVHQWZHDNHUPXFRDGKHVLRQIRUFHFRPSDUHGWRDQLRQLF SRO\PHUV0RUWD]DYL0RJKLPL 7KHUHLVDQHZFODVVRIVXEVWDQFHVEHLQJLGHQWLHG DVELRDGKHVLYH7KLVFODVVFRQVLVWVRIHVWHUJURXSVRIIDWW\ DFLGVVXFKDVJO\FHU\OPRQRROHDWHDQGJO\FHU\OPRQR OLQROHDWHDEOHWREXLOGOLTXLGFU\VWDOVZKLFKLQWXUQFDQ DFWDVFRQWUROOHGUHOHDVHV\VWHPV7KHVHIDWW\DFLGVEXLOG O\RWURSLFOLTXLGFU\VWDOOLQHPHVRSKDVHVLQWKHSUHVHQFH RIZDWHUDWERG\WHPSHUDWXUH/LTXLGFU\VWDOVFDQEH FRQVLGHUHGVWUXFWXUHVRIPLFHOOHVRUGHUHGLQDPROHFXODU DUUDQJHPHQWFKDUDFWHUL]HGE\DOWHUQDWHK\GURSKRELFDQG K\GURSKLOLFUHJLRQV'LIIHUHQWOLTXLGFU\VWDOOLQHIRUPV LQFOXGLQJODPHOODUKH[DJRQDODQGFXELFFDQEHEXLOWDV WKHVXUIDFWDQWFRQFHQWUDWLRQLQFUHDVHV0DOPVWHQ &XELFSKDVHIDYRUVWKHFRQWUROOHGUHOHDVHRIGUXJVVLQFH LWKDVDVWUXFWXUHPDGHXSRIWULGLPHQVLRQDOFXUYHGOLSLG
Page 7
0XFRDGKHVLYHGUXJGHOLYHU\V\VWHPV ELOD\HUVVHSDUDWHGE\FRQJUXHQWZDWHUFKDQQHOV7KLV VWUXFWXUHKDVWKHDSSHDUDQFHRIKLJKO\YLVFRXVWUDQVSDUHQW JHO'XHWRWKLVUHODWLYHO\KLJKYLVFRVLW\LWLVGLIFXOWWRDG PLQLVWHURQDQ\PXFRXVPHPEUDQH,QRUGHUWRFLUFXPYHQW WKHDGPLQLVWUDWLRQSUREOHPVDOHVVYLVFRXVPHVRSKDVH HJWKHODPHOODUSKDVHFDQEHXVHG,QWKHVHLQVWDQFHVWKLV SKDVHLVFRQVLGHUHGDSUHFXUVRURIWKHFXELFSKDVH,QWKH FDVHRIO\RWURSLFPHVRSKDVHVWKHSUHFXUVRUDEVRUEVZDWHU LQVLWX DQGVSRQWDQHRXVO\EXLOGVWKHFXELFSKDVH%UXVFKL HWDO 1LHOVHQ6FKXEHUW+DQVHQ 6RPHK\GURJHOVGRQRWEXLOGOLTXLGFU\VWDOVEXWDUH DEOHWRJHOLI\ LQVLWX DIWHUH[SRVXUHWRDQH[WHUQDOVWLPXOXV 7KHVHDUHWKHVRFDOOHGHQYLURQPHQWDOVHQVLWLYHSRO\PHUV DQGDUHFODVVLILHGDVWKHUPRVHQVLWLYHHJSROR[DPHUV DQGFDUERPHUV%UXVFKL HWDO 3DUN HWDO S+VHQVLWLYHHJSRO\DFU\OLFDFLGSUHVHQWLQJLQFUHDVHG YLVFRVLW\DWKLJKHUS+YDOXHVJOXFRVHVHQVLWLYHHJSRO\ PHUVOLQNHGWRFRQFDYDOLQ$HOHFWULFVLJQDOVHQVLWLYHHJ SRO\PHWKDFU\OLFDFLGOLJKWVHQVLWLYHOLNHK\DOXURQLFDFLG 4LX3DUNRULRQLFFRQFHQWUDWLRQVHQVLWLYHVXFK DVJHOODQJXP+DJHUVWURP HWDO $OOWKHVHVWLPXOL DUHIRXQGLQWKHRUJDQLVPPDNLQJWKHVHSRO\PHUVRIJUHDW SRWHQWLDOIRUXVHLQWKHGHVLJQRIFRQWUROOHGUHOHDVHV\VWHPV 4LX3DUN 0XFRDGKHVLRQIRUJHOVIRUPHGE\ERWKOLTXLG FU\VWDOVDQGE\HQYLURQPHQWDOVHQVLWLYHSRO\PHUVFDQEH H[SODLQHGE\WKHLUUKHRORJLFDOSURSHUWLHV7KHVHSURSHUWLHV GHFUHDVHWKHPXFRFLOLDUFOHDUDQFHDQGLQFUHDVHWKHFRQ WDFWWLPHRIWKHIRUPXODWLRQZLWKWKHPXFRXVPHPEUDQH %UXVFKL HWDO 1LHOVHQ6FKXEHUW+DQVHQ Second generation mucoadhesive materials 6WXGLHVRQQRYHOPXFRDGKHVLYHV\VWHPVLQYROYH WKHXVHRIPXOWLIXQFWLRQDOPDWHULDOV$QLGHDOSRO\PHU VKRXOGH[KLELWWKHDELOLW\WRLQFRUSRUDWHERWKK\GURSKLOLF DQGOLSRSKLOLFGUXJVVKRZPXFRDGKHVLYHSURSHUWLHVLQLWV VROLGDQGOLTXLGIRUPVLQKLELWORFDOHQ]\PHVRUSURPRWH DEVRUSWLRQEHVSHFLFIRUDSDUWLFXODUFHOOXODUDUHDRUVLWH VWLPXODWHHQGRF\WRVLVDQGQDOO\WRKDYHDEURDGVDIHW\ UDQJH/HH3DUN5RELQVRQ 7KHVHQRYHOPXOWLIXQFWLRQDOPXFRDGKHVLYHV\VWHPV DUHFODVVLHGDVVHFRQGJHQHUDWLRQSRO\PHUV/HH3DUN 5RELQVRQ7KH\DUHDQDOWHUQDWLYHWRQRQVSHFLF ELRDGKHVLYHV6PDUWEHFDXVHWKH\ELQGRUDGKHUHWR VSHFLFFKHPLFDOVWUXFWXUHVRQWKHFHOORUPXFXVVXUIDFH *RRGH[DPSOHVRIWKHVHPROHFXOHVDUHOHFWLQVLQYDVLQV PEULDOSURWHLQV :RRGOH\ DQWLERGLHV&KRZGDU\ 5DRDQGWKRVHREWDLQHGE\WKHDGGLWLRQRIWKLRO JURXSVWRNQRZQPROHFXOHV%UDYR2VXQD HWDO /HFWLQVDUHLPPXQRJHQLFYHJHWDOJO\FRSURWHLQVWKDW VSHFLFDOO\UHFRJQL]HVXJDUPROHFXOHV7KH\DUHDEOHWR QRQFRYDOHQWO\ELQGWRJO\FRVLODWHGFRPSRQHQWVRIWKH FHOOXODUPHPEUDQHEXWQRWRIWKHPXFXVDQGDGKHVLRQFDQ WKHUHIRUHEHFDOOHGF\WRDGKHVLRQ7KURXJKWKHWUDQVPLV VLRQRIDFHOOXODUVLJQDOWKLVVSHFLFERQGFDQUHVXOWQRW RQO\LQELRDGKHVLRQEXWDOVRLQFHOOXODULQWHUQDOL]DWLRQE\ GLIIHUHQWO\VRVRPDODQGQRQO\VRVRPDOPHFKDQLVPV/HKU 7KHPRVWFRPPRQO\IRXQGOHFWLQVDUHWKRVHLVROD WHGIURP $EUXVSUHFDWURLXV$JDULFXVELVSRUXV$QJXLOOD DQJXLOOD$UDFKLVK\SRJDHD3DQGHLUDHDVLPSOLFLIROLD DQG %DXKLQLDSXUSXUHD &KRZGDU\5DR %DFWHULDOLQYDVLQVDUHSURWHLQVIURPWKHPHPEUDQH RI WKDWVWLPXODWHIDJRF\WRVLV DWFHOOXODUPHPEUDQHWKURXJKOLQNDJHZLWKLQWHJULQUHFHS WRUV&KRZGDU\5DR/HKU:RRGOH\ %DFWHULDOPEULDOSURWHLQVDUHDEOHWRDGKHUHWRWKH HSLWKHOLDOVXUIDFHRIHU\WKURF\WHV7KLVDGKHVLRQLVUHODWHG WRWKHSDWKRJHQLFLW\RIWKHEDFWHULD%DFWHULDODGKHVLYH IDFWRUVFDQEHDQHIILFLHQWPHFKDQLVPRILPSURYLQJ DGKHVLRQRIPXFRDGKHVLYHDJHQWVXVHGLQUHOHDVHV\VWHPV &KRZGDU\5DR $QWLERGLHVFDQEHSURGXFHGDJDLQVWVHOHFWHGPR OHFXOHVSUHVHQWRQWKHPXFXVVXUIDFH'XHWRWKHLUKLJK VSHFLFLW\DQWLERGLHVFDQEHDUDWLRQDOFKRLFHDVSRO\PHULF OLJDQGLQWKHGHYHORSPHQWRIVLWHVSHFLFPXFRDGKHVLYHV 7KLVVWUDWHJ\FDQEHXVHIXOIRULQVWDQFHLQGUXJVWDUJHWLQJ WXPRUWLVVXHV&KRZGDU\5DR 7KLRODWHGSRO\PHUVDUHREWDLQHGE\WKHDGGLWLRQRI FRQMXJDWHGVXOGU\OJURXSV*UDERYDF*XJJL%HUQNRS 6FKQUFK%UDYR2VXQD HWDO VKRZHGWKDW WKLRODWHGFKLWRVDQLQFUHDVHGPXFRDGKHVLYHSURSHUWLHVGXH WRIRUPDWLRQRIGLVXOGHEULGJHVZLWKF\VWHLQGRPDLQVRI JO\FRSURWHLQVRIWKHPXFXV$GGLWLRQDOO\WKHVHSURGXFWV SURPRWHGPXFXVSHUPHDWLRQE\DPHFKDQLVPRIJOXWD WKLRQHUHJHQHUDWLRQ)LQDOO\WKH\SRVVHVVDQWLSURWHDVH DFWLYLW\GXHWRWKHLUELQGLQJDELOLW\ZLWKGLYDOHQWFDWLRQV VXFKDV]LQFDQGPDJQHVLXPZKLFKDUHFRIDFWRUVIRU PDQ\SURWHDVHV$OOWKHVHFKDUDFWHULVWLFVPDNHWKLRODWHG FKLWRVDQDSURPLVLQJPDWHULDOIRUDGPLQLVWHULQJSHSWLGHV DQGSURWHLQVLQPXFRXVPHPEUDQH%UDYR2VXQD HWDO $QRWKHUVWXG\FDUULHGRXWE\*UDERYDF*XJJL DQG%HUQNRS6FKQUFK HVWDEOLVKHG DUDQNLQJRI WKHPRVWVWXGLHGSRO\PHUVVKRZLQJWKDWERWKWKLRODWHG FKLWRVDQDQGSRO\FDUERSKLODUHWKHPRVWPXFRDGKHVLYH &XUUHQWO\WKHDGGLWLRQRIHOHPHQWVRIVHQVLWL]DWLRQ DQGUHFRJQLWLRQFRQWLQXHEHLQJXVHGIRUWKHGHVLJQRI SRO\PHUVZLWKPRUHLQWHOOLJHQWPHFKDQLVPVRIPXFRDGKH VLRQ%\ELQGLQJIXQFWLRQDOJURXSVZLWKLQSRO\PHUFKDLQV K\GURJHOVFDQEHPDGHPRUHVHQVLWLYHWRVXUURXQGLQJ HQYLURQPHQWDOFRQGLWLRQVOLNHWHPSHUDWXUHPRLVWXUHS+ HOHFWULFDOHOGVDQGLRQLFIRUFHV3HSSDV+XDQJ
Page 8
)&&DUYDOKR0/%UXVFKL5&(YDQJHOLVWD03'*UHPLmR +XDQJ HWDO SURSRVHGDPHFKDQLVPLQ ZKLFKXQLWVRIWKHUHOHDVHV\VWHPFDQVSHFLFDOO\ELQG DWWKHWDUJHWVXUIDFH&HUWDLQDPLQRDFLGVHTXHQFHVKDYH FRPSOHPHQWDU\FKDLQVDWPXFRXVPHPEUDQHDQGFHOOXODU VXUIDFH2QFRQWDFWZLWKWKHPXFRXVPHPEUDQHWKH\FDQ SURPRWHDGKHVLRQE\ELQGLQJWRVSHFLFJO\FRSURWHLQVRQ WKLVVXUIDFH8VLQJWKLVVDPHPHFKDQLVPLQWKHFDVHRI VRPHGLVHDVHVFKDQJHVRFFXULQWKHJO\FRSURWHLQVZKLFK FDQEHDWWDFNHGE\FRPSOHPHQWDU\DPLQRDFLGVHTXHQ FHVOLQNHGWRDUHOHDVHV\VWHPWKHUHIRUHLQFUHDVLQJWKH DIQLW\IRUGLVHDVHGFHOOV7KHPDMRUSUREOHPZLWKWKLV VWUDWHJ\LVQGLQJWKHJO\FRSURWHLQVDQGWKHLUDOWHUDWLRQV LQFDVHRIGLVHDVHV+XDQJ HWDO :LWKWKHDGYHQWRIPRUHLQWHOOLJHQWPXFRDGKHVLYH PDWHULDOVLWLVSRVVLEOHWRRIIHUDXQLTXHFDUU\LQJFKDUDFWH ULVWLFIRUPDQ\GUXJV+XDQJ HWDO 7KHVHFDQEHGH VLJQHGIRUDGKHULQJRQWRDQ\PXFRXVPHPEUDQHIRUH[DP SOHRFXODUEXFFDOUHVSLUDWRU\XULQDU\RUJDVWURLQWHVWLQDO HWF0XFRDGKHVLYHPDWHULDOVFDQLPSURYHELRDYDLODELOLW\ GUXJDEVRUSWLRQDQGWUDQVSRUWZKLOHUHGXFLQJXQGHVLUDEOH V\VWHPLFHIIHFWV,QVXPPDU\ZLWKWKHVHPDWHULDOVLWLV SRVVLEOHWRGHYHORSQRYHOV\VWHPVIRUGUXJVFXUUHQWO\XVHG LQWKHUDS\DQGWRREWDLQQHZSURGXFWVDWORZFRVW METHODS OF ANALYZING MUCOADHE SION 1RWHFKQRORJ\KDVVWLOOEHHQGHYHORSHGVSHFLFDOO\ WRDQDO\]HPXFRDGKHVLRQ0RVWRIWKHWHVWVDYDLODEOHZHUH DGDSWHGIURPRWKHUSUHH[LVWLQJWHFKQLTXHVEXWDUHXVHIXO DQGQHFHVVDU\IRUVHOHFWLQJWKHSURPLVLQJFDQGLGDWHVDV PXFRDGKHVLYHVDVZHOODVLQHOXFLGDWLQJWKHLUPHFKDQLVPV RIDFWLRQ In vitro and ex vivo tests ,QYLWURH[YLYR WHVWVDUHLPSRUWDQWLQWKHGHYHORS PHQWRIDFRQWUROOHGUHOHDVHELRDGKHVLYHV\VWHPEHFDXVH WKH\FRQWULEXWHWRVWXGLHVRISHUPHDWLRQUHOHDVHFRP SDWLELOLW\PHFKDQLFDODQGSK\VLFDOVWDELOLW\VXSHUFLDO LQWHUDFWLRQEHWZHHQIRUPXODWLRQDQGPXFRXVPHPEUDQH DQGVWUHQJWKRIWKHELRDGKHVLYHERQG7KHVHWHVWVFDQVL PXODWHDQXPEHURIDGPLQLVWUDWLRQURXWHVLQFOXGLQJRUDO EXFFDOSHULRGRQWDOQDVDOJDVWURLQWHVWLQDOYDJLQDODQG UHFWDO7KH LQYLWUR DQG H[YLYR WHVWVPRVWSUHYDOHQWLQWKH OLWHUDWXUHDUHUHSRUWHGEHORZ Techniques utilizing gut sac of rats 7KHHYHUWHGJXWVDFWHFKQLTXHLVDQH[DPSOHRIDQ H[YLYR PHWKRG,WKDVEHHQXVHGVLQFHWRVWXG\LQ WHVWLQDOWUDQVSRUW6DQWRV HWDO DSSOLHGWKLVPHWKRG RQPXFRDGKHVLRQDVVD\V,WLVHDV\WRUHSURGXFHDQGFDQ EHSHUIRUPHGLQDOPRVWDOOODERUDWRULHV)LJXUHVFKHPD WLFDOO\UHSUHVHQWVWKHWHFKQLTXH$VHJPHQWRILQWHVWLQDO WLVVXHLVUHPRYHGIURPWKHUDWHYHUWHGDQGRQHRILWVHQGV VXWXUHGDQGILOOHGZLWKVDOLQH7KHVDFVDUHLQWURGXFHG LQWRWXEHVFRQWDLQLQJWKHV\VWHPXQGHUDQDO\VLVDWNQRZQ FRQFHQWUDWLRQVVWLUUHGLQFXEDWHGDQGWKHQUHPRYHG7KH SHUFHQWDGKHVLRQUDWHRIWKHUHOHDVHV\VWHPRQWRWKHVDF LVGHWHUPLQHGE\VXEWUDFWLQJWKHUHVLGXDOPDVVIURPWKH LQLWLDOPDVV6DQWRV HWDO 2WKHUWHFKQLTXHVXVHQRQHYHUWHGJXWVDF7DNHXFKL HWDO OOHGUDWVLQWHVWLQHVZLWKOLSRVRPHVXVSHQ VLRQV7KHVDFVZHUHVHDOHGDQGLQFXEDWHGLQVDOLQH$IWHU DVWLSXODWHGWLPHWKHQXPEHURIOLSRVRPHVDGKHUHGEHIRUH DQGDIWHU LQFXEDWLRQZDVDVVHVVHGZLWKDFRXOWHU FRXQWHUDQGWKHSHUFHQWPXFRDGKHVLYHZDVH[SUHVVHGE\ HTXDWLRQ7DNHXFKL HWDO 7KHPXFRDGKHVLYHHIIHFWRIDV\VWHPFDQDOVREH HYDOXDWHGE\LQFUHDVHVLQJDVWURLQWHVWLQDOWUDQVLW*RWR HW DO LQFRUSRUDWHGXRUHVFHQWWUDFHUVLQWRDV\VWHP DQGTXDQWLHGWKHPE\XRUHVFHQFHVSHFWURVFRS\LQWKH VWRPDFKDQGLQWHVWLQDOPXFXVDVDIXQFWLRQRIWLPH Tests measuring mucoadhesive strength 0RVW LQYLWURH[YLYR PHWKRGRORJLHVIRXQGLQWKH OLWHUDWXUHDUHEDVHGRQWKHHYDOXDWLRQRIPXFRDGKHVLYH VWUHQJWKWKDWLVWKHIRUFHUHTXLUHGWREUHDNWKHELQGLQJ EHWZHHQWKHPRGHOPHPEUDQHDQGWKHPXFRDGKHVLYH ),*85( (YHUWHGJXWVDFSURFHGXUH
Page 9
0XFRDGKHVLYHGUXJGHOLYHU\V\VWHPV 'HSHQGLQJRQWKHGLUHFWLRQLQZKLFKWKHPXFRDGKHVLYH LVVHSDUDWHGIURPWKHVXEVWUDWHLVLWSRVVLEOHWRREWDLQWKH GHWDFKPHQWVKHDUDQGUXSWXUHWHQVLOHVWUHQJWKV+lJHUV WU|PDVLQGLFDWHGLQ)LJXUH 7KHIRUFHPRVWIUHTXHQWO\HYDOXDWHGLQVXFKWHVWVLV UXSWXUHWHQVLOHVWUHQJWK%URPEHUJ HWDO %UXVFKL HWDO +lJHUVWU|P*HQHUDOO\WKHHTXLSPHQW XVHGLVDWH[WXUHDQDO\]HU)LJXUHRUDXQLYHUVDOWHVWLQJ PDFKLQH,QWKLVWHVWWKHIRUFHUHTXLUHGWRUHPRYHWKHIRU PXODWLRQIURPDPRGHOPHPEUDQHLVPHDVXUHGZKLFKFDQ EHDGLVFFRPSRVHGRIPXFLQ%UXVFKL HWDO DSLHFH RIDQLPDOPXFRXVPHPEUDQHJHQHUDOO\SRUFLQHQDVDO PXFXV+lJHUVWU|PRULQWHVWLQDOPXFXVIURPUDWV %URPEHUJ HWDO %DVHGRQUHVXOWVDIRUFHGLVWDQFH FXUYHFDQEHSORWWHGZKLFK\LHOGVWKHIRUFHUHTXLUHGWR GHWDFKWKHPXFLQGLVFIURPWKHVXUIDFHZLWKWKHIRUPX ODWLRQ%UXVFKL HWDO WKHWHQVLOHZRUNDUHDXQGHU WKHFXUYHGXULQJWKHGHWDFKPHQWSURFHVVWKHSHDNIRUFH DQGWKHGHIRUPDWLRQWRIDLOXUH+lJHUVWU|P7KLV PHWKRGLVPRUHIUHTXHQWO\XVHGWRDQDO\]HVROLGV\VWHPV OLNHPLFURVSKHUHV&KRZGDU\5DRDOWKRXJKWKHUH DUHDOVRVWXGLHVRQVHPLVROLGPDWHULDOV%URPEHUJ HWDO %UXVFKL HWDO ,QDGGLWLRQWRUXSWXUHWHQVLOHVWUHQJWKWKHWH[WXUH DQDO\]HUFDQDOVRDVLQIHUUHGE\LWVQDPHHYDOXDWHWKH WH[WXUHRIWKHIRUPXODWLRQVDQGDVVHVVRWKHUPHFKDQLFDO FIGURE 7 'LIIHUHQWIRUFHVHYDOXDWHGLQPXFRDGKHVLRQWHVWV FIGURE 8 %LRDGKHVLRQWHVWXVLQJWKHWH[WXUHDQDO\]HU SURSHUWLHVRIWKHV\VWHP$PRELOHDUPFRQWDLQLQJDQ DQDO\WLFDOSUREHIRUFHVGRZQLQWRDVDPSOHKHOGLQDDVN SODFHGRQWKHHTXLSPHQWVSODWIRUP6SHHGUDWHWLPHDQG GHSWKDUHSUHVHW)URPWKHUHVXOWLQJIRUFHWLPHDQGIRUFH GLVWDQFHSORWVLWLVSRVVLEOHWRFDOFXODWHWKHKDUGQHVVIRUFH UHTXLUHGWRUHDFKDJLYHQGHIRUPDWLRQFRPSUHVVLELOLW\ ZRUNUHTXLUHGWRGHIRUPWKHSURGXFWGXULQJWKHFRP SUHVVLRQDQGDGKHVLYHQHVVZRUNUHTXLUHGWRRYHUFRPH WKHDWWUDFWLRQIRUFHVEHWZHHQWKHVXUIDFHVRIVDPSOHDQG SUREH8VLQJWKLVWHFKQLTXHLWLVSRVVLEOHWRSHUIRUPD SUHYLRXVHYDOXDWLRQRIWKHPDWHULDOVDGKHVLYHFDSDFLW\ HYLGHQFLQJPXFRDGKHVLRQSURSHUWLHV%UXVFKL 0XFRDGKHVLRQVWUHQJWKFDQDOVREHPHDVXUHGLQ WHUPVRIVKHDUVWUHQJWK7KLVWHVWPHDVXUHVWKHIRUFH UHTXLUHGWRVHSDUDWHWZRSDUDOOHOJODVVVOLGHVFRYHUHG ZLWKWKHSRO\PHUDQGZLWKDPXFXVOP%UXVFKL)UHL WDV&KRZGDU\5DR7KLVFDQDOVREHGRQH XVLQJ:LOKHP\VPRGHO)LJXUHLQZKLFKDJODVVSODWH LVVXVSHQGHGE\DPLFURIRUFHEDODQFHDQGLPPHUVHGLQD VDPSOHRIPXFXVXQGHUFRQWUROOHGWHPSHUDWXUH7KHIRUFH UHTXLUHGWRSXOOWKHSODWHRXWRIWKHVDPSOHLVWKHQPHDVX UHGXQGHUFRQVWDQWH[SHULPHQWDOFRQGLWLRQV$KXMD.KDU $OL$OWKRXJKPHDVXUHVWDNHQE\WKLVPHWKRGDUH UHSURGXFLEOHWKHWHFKQLTXHLQYROYHVQRELRORJLFDOWLVVXH DQGWKHUHIRUHGRHVQRWSURYLGHDUHDOLVWLFVLPXODWLRQRI ELRORJLFDOFRQGLWLRQV:RQJ :LOKHP\VSODWHWHFKQLTXHRUWKHPLFURIRUFHED ODQFHWHFKQLTXHFDQDOVREHPRGLHGLQRUGHUWRPHDVXUH WKHVSHFLFDGKHVLRQIRUFHRIPLFURSDUWLFOHV&KRZGDU\ 5DR+lJHUVWU|P7KLVLQYROYHVWKHXVHRI DPLFURWHQVLRPHWHUDQGDPLFURIRUFHEDODQFH)LJXUH DQGLVVSHFLF\LHOGLQJERWKFRQWDFWDQJOHDQGVXUIDFH WHQVLRQ7KHPXFRXVPHPEUDQHLVSODFHGLQDVPDOOPR ELOHFKDPEHUZLWKERWKS+DQGSK\VLRORJLFDOWHPSHUDWXUH FRQWUROOHG$XQLTXHPLFURVSKHUHLVDWWDFKHGE\DWKUHDGWR WKHVWDWLRQDU\PLFUREDODQFH7KHFKDPEHUZLWKWKHPXFRXV FIGURE 9 $SSDUDWXVWRGHWHUPLQHPXFRDGKHVLRQ LQYLWUR XVLQJ:LOKHP\VWHFKQLTXH
Page 10
)&&DUYDOKR0/%UXVFKL5&(YDQJHOLVWD03'*UHPLmR PHPEUDQHLVUDLVHGXQWLOLWFRPHVLQWRFRQWDFWZLWKWKH PLFURVSKHUHDQGDIWHUFRQWDFWWLPHLVORZHUHGEDFNWR WKHLQLWLDOSRVLWLRQ0DWKLRZLW]&KLFNHULQJ/HKU )ROORZLQJWKHWUDMHFWRU\DQGZLWKWKHDLGRIVRIWZD UHUHVXOWVFDQEHREWDLQHGIRUVHYHUDOSDUDPHWHUVVXFKDV IUDFWXUHVWUHQJWKGHIRUPDWLRQDQGUXSWXUHWHQVLOHVWUHQJWK IURPDORDG YHUVXV GHIRUPDWLRQFXUYHDVVKRZQLQ)LJXUH 0DWKLRZLW]&KLFNHULQJ/HKU 7KHPLFURIRUFHEDODQFHLVQRWLQGLFDWHGIRUPLFURV SKHUHVVPDOOHUWKDQ PEXWKDVWKHDGYDQWDJHRI VLPXODWLQJSK\VLRORJLFDOFRQGLWLRQVDQGSURYLGLQJUHVXOWV DWDPRUHPLFURVFRSLFOHYHOEHVLGHVEHLQJPRUHUHSURGX FLEOHDQGVHQVLWLYH0DWKLRZLW]&KLFNHULQJ/HKU Rheological methods 7KLVFDWHJRU\RIPHWKRGVDUHDOOFDUULHGRXW LQYLWUR DQGZHUHUVWSURSRVHGE\+DVVDQDQG*DOORZKR XVHGYLVFRVLPHWULFDVVD\VWRPDFURVFRSLFDOO\DQDO\]HWKH IRUPXODWLRQPXFLQLQWHUDFWLRQ)URPWKLVWHVWLWLVSRVVL EOHWRREWDLQWKHPXFRDGKHVLRQIRUFHE\PRQLWRULQJWKH YLVFRVLPHWULFFKDQJHVRIWKHV\VWHPFRQVWLWXWHGE\WKH PL[WXUHRIWKHSRO\PHUFKRVHQDQGPXFLQ7KHHQHUJ\RI WKHSK\VLFDODQGFKHPLFDOERQGVRIWKHPXFLQSRO\PHU LQWHUDFWLRQFDQEHWUDQVIRUPHGLQWRPHFKDQLFDOHQHUJ\RU ZRUN7KLVZRUNZKLFKFDXVHVWKHUHDUUDQJHPHQWVRIWKH PDFURPROHFXOHVLVWKHEDVLVRIWKHFKDQJHLQYLVFRVLW\$ ZD\WRDQDO\]HWKHFRHIFLHQWRIYLVFRVLW\RIDK\GURSKL OLFGLVSHUVLRQFRQWDLQLQJPXFLQSOXVWKHPXFRDGKHVLYH SRO\PHULVWKURXJKWKHFRQWULEXWLRQRIHDFKFRPSRQHQW ZKLFKUHVXOWVLQHTXDWLRQ W P S E ZKHUH LVWKHFRHIFLHQWRIYLVFRVLW\RIWKHV\VWHPDQG DQG DUHWKHFRHIFLHQWVRIYLVFRVLW\RIPXFLQDQG ELRDGKHVLYHSRO\PHUUHVSHFWLYHO\7KHELRDGKHVLRQFRP SRQHQW FDQEHREWDLQHGIURPHTXDWLRQUHVXOWLQJLQ HTXDWLRQ E W P )RUHTXDWLRQVDQGWREHYDOLGDOOFRPSRQHQWV VKRXOGEHPHDVXUHGDWWKHVDPHFRQFHQWUDWLRQWHPSHUD WXUHWLPHDQGVKHDUJUDGLHQW7KHELRDGKHVLRQIRUFH LV GHWHUPLQHGE\HTXDWLRQ ) ZKHUHLVWKHVKHDUJUDGLHQW 7KHPDLQGLVDGYDQWDJHRIWKLVPHWKRGLVWKH EUHDNGRZQRIWKHSRO\PHUDQGPXFLQQHWZRUNXQGHU FRQWLQXRXVRZ7RDYRLGWKLVSUREOHPWKHPHWKRGZDV DGDSWHGXVLQJRVFLOODWRU\UKHRORJ\&DOOHQV HWDO +lJHUVWU|P%DVHGRQWKHVDPHDVVXPSWLRQWKDW WKHUKHRORJLFDOUHVSRQVHRISRO\PHUPXFLQPL[WXUHVKRXOG EHJUHDWHUWKDQWKHFRQWULEXWLRQVIURPWKHJHODQGLVRODWHG PXFLQDSDUDPHWHUFDOOHGUKHRORJLFDOV\QHUJLVPFDQEH REWDLQHG7KLVPHWKRGLVPRUHDGYDQWDJHRXVWKDQWKH RULJLQDOVLQFHRVFLOODWRU\UKHRORJ\LVDQRQGHVWUXFWLYH WHFKQLTXHDQGVLPXOWDQHRXVO\PHDVXUHVYLVFRVLW\DQG HODVWLFEHKDYLRUDQGFDQEHXVHGWRGHWHUPLQHPXFRD GKHVLRQEHWZHHQSRO\PHUVDQGPXFLQ&DOOHQV HWDO 7KHHYDOXDWLRQRIUKHRORJLFDOV\QHUJLVPFDQEH FIGURE 11 D7\SLFDOORDG YHUVXV GHIRUPDWLRQFXUYHE 3URJUHVVLRQRIIRUFHVDSSOLHGIRUFRUUHVSRQGLQJJUDSK D E FIGURE 10 0LFUREDODQFHPHWKRGIRUPHDVXULQJ PXFRDGKHVLRQ
Page 11
0XFRDGKHVLYHGUXJGHOLYHU\V\VWHPV GRQHWKURXJKWZRW\SHVRIRVFLOODWRU\DVVD\VVWUHVV VZHHSDQGIUHTXHQF\VZHHS&HXOHPDQV9LQFNLHU /XGZLJ ,QVWUHVVVZHHSWKHHODVWLF*DQGYLVFRXV* PRGXOLDUHREWDLQHGXQGHUFRQVWDQWIUHTXHQF\7KLVLVXVHG WRLQYHVWLJDWHWKHLQXHQFHRIVWUHVVRQWKHG\QDPLFPR GXOXVZKLFKVKRXOGEHREWDLQHGLQWKHOLQHDUYLVFRHODVWLF UHJLRQWKDWLVWKHUHJLRQZKHUHWKHPDWHULDOUHVSRQVHLV FKDUDFWHULVWLFIRULWVPLFURVWUXFWXUH$ERYHWKLVUHJLRQ WKHVWUXFWXUHLVGHVWUR\HG7KHPDJQLWXGHRIWKHPRGXOL LVDTXDOLWDWLYHLQGLFDWLRQRIWKHV\VWHPVWUXFWXUH7KUHH VLWXDWLRQVFDQEHIRXQGIRUSRO\PHULFGLVSHUVLRQ*!!* IRUDFKHPLFDOO\LQWHUFRQQHFWHGV\VWHP*!*IRUFKDLQV ZLWKVHFRQGDU\ERQGVDQG**IRUGLVSHUVLRQVZLWK SK\VLFDOO\ERXQGPROHFXOHV7KHTXDQWLWDWLYHPHDVXUH RIUKHRORJLFDOV\QHUJLVP*FDQEHFDOFXODWHGHLWKHU LQUHODWLRQWR*RU*&DOOHQV HWDO &HXOHPDQV 9LQFNLHU/XGZLJDVVKRZQLQHTXDWLRQ ,QIUHTXHQF\VZHHSVWUHVVLVPDLQWDLQHGFRQVWDQW 7KHVWUXFWXUHRIWKHV\VWHPFDQUHPDLQLQWDFWGXULQJWKH DVVD\LILWLVFRQGXFWHGLQWKHOLQHDUYLVFRHODVWLFUHJLRQ 8QGHUFRQVWDQWVWUHVVDQGDWORZIUHTXHQFLHVEHWWHUVWUXF WXUHGV\VWHPVSUHVHQWJUHDWHUHODVWLFPRGXOXVWKDQYLVFRXV PRGXOXVDQGERWKDUHLQGHSHQGHQWRIIUHTXHQF\2QDORJ ORJJUDSKWKH\DUHUHSUHVHQWHGE\DFRQVWDQWVWUDLJKWOLQH )RUOHVVRUJDQL]HGV\VWHPVG\QDPLFPRGXOLDUHGHSHQGHQW RQWKHIUHTXHQF\DQGDVORSHLVREVHUYHG&DOOHQV HWDO &HXOHPDQV9LQFNLHU/XGZLJ 7KLVWHVWHQDEOHVDQDO\VLVRIWKHG\QDPLFYLVFRHODV WLFSDUDPHWHUVFRUUHVSRQGLQJWRWKHVDPHIUHTXHQF\DVD IXQFWLRQRISRO\PHURUPXFLQFRQFHQWUDWLRQ\LHOGLQJWKH UKHRORJLFDOEHKDYLRULQUHODWLRQWRWKHFRQFHQWUDWLRQRIWKH V\VWHPFRQVWLWXHQWV+lJHUVWU|P +lJHUVWU|PUHYHDOVDQDOWHUQDWLYHSDUDPHWHU RIUKHRORJLFDOV\QHUJLVPFDOOHGUHODWLYHUKHRORJLFDOV\ QHUJLVPSDUDPHWHU * UHODWLYH FDOFXODWHGIURPHTXDWLRQ DQGZLWKZKLFKLWLVSRVVLEOHWRTXDQWLWDWLYHO\FRPSDUHWKH IRUFHRISRO\PHUPXFLQPL[WXUHZLWKWKHLVRODWHGSRO\PHU ZKHUH * LVWKHUKHRORJLFDOV\QHUJLVPJLYHQE\WKHGL IIHUHQFHEHWZHHQHODVWLFPRGXOXVRIWKHPL[WXUH * PL[WXUH DQGWKHHODVWLFPRGXOXVRIWKHSRO\PHU * +RZHYHU * UHODWLYH KDVWKHGLVDGYDQWDJHRIDQHJD WLYHOLPLWXSWRZKLOHWKHSRVLWLYHYDOXHVUXQWRLQ QLW\7KHUHIRUHWKHPDJQLWXGHRISRVLWLYHYDOXHVFDQQRW EHFRPSDUHGZLWKWKDWRIQHJDWLYHYDOXHV7KXVDQHZ UHODWLYHSDUDPHWHUZDVSURSRVHGFDOOHGWKHORJDULWKPLF UHODWLRQRIHODVWLFPRGXOHORJ * ZKLFKLVJLYHQE\WKH UDWLREHWZHHQHODVWLFPRGXOXVRIWKHPL[WXUH PL[ DQG WKHHODVWLFPRGXOXVRIWKHSRO\PHU * S DVLQGLFDWHGLQ HTXDWLRQ 7KLVSDUDPHWHURIIHUVWKHDGYDQWDJHWKDWERWKSR VLWLYHDQGQHJDWLYHYDOXHVKDYHWKHVDPHPDJQLWXGHDQG DUHWKHUHIRUHFRPSDUDEOH)RULQVWDQFHWKHYDOXHPHDQV WKDW*RIWKHPL[WXUHLVIROGJUHDWHUWKDQWKDWRIWKH LVRODWHGSRO\PHU+lJHUVWU|P 5KHRORJLFDOWHVWVDUHSHUIRUPHGWRWDOO\ LQYLWUR DQGFRQVHTXHQWO\DUHFRQGXFWHGLQFRPELQDWLRQZLWK WKHUXSWXUHWHQVLOHVWUHQJWKWHVWPRVWIUHTXHQWO\XVHGLQ VWXGLHVRQPXFRDGKHVLRQ7KHH[SHULPHQWDOFRQGLWLRQV RIERWKWHVWVGLIIHUDQGWKHUHDUHFDVHVLQZKLFKWKHWH FKQLTXHVDUHFRPSOHPHQWDU\5KHRORJ\PHDVXUHVWKH PHFKDQLFDOSURSHUWLHVRIWKHV\VWHPLHWKHUHVLVWDQFH DJDLQVWRZDQGGHIRUPDWLRQDVVHVVLQJWKHFKDQJHVWKH V\VWHPXQGHUJRHVLQWKHSUHVHQFHRIPXFLQ+RZHYHU UKHRORJ\GRHVQRWSURYLGHDQ\GLUHFWLQIRUPDWLRQRQZKDW RFFXUVDWWKHLQWHUIDFHEHFDXVHWKHWZRSKDVHVPXFLQ DQGSRO\PHUDUHPL[HGWRJHWKHUSULRUWRWKHH[SHUL PHQW,QWKHUXSWXUHWHQVLOHVWUHQJWKWHVWWKHLQWHUIDFH LVDUWLFLDOO\FUHDWHG(YHQZLWKWKLVGLIIHUHQFHZKHQ WKHPXFLQSRO\PHUSURGXFHVUKHRORJLFDOV\QHUJLVPD FRUUHVSRQGLQJVWUXFWXUHRUJDQL]DWLRQLVREVHUYHGDWWKH PXFRDGKHVLYHLQWHUIDFH7KHUXSWXUHWHQVLOHVWUHQJWKWHVW FDQEHDSSOLHGWRVROLGVDQGVHPLVROLGVZKLOHUKHRORJ\ LVDSSOLFDEOHWRVHPLVROLGVDQGOLTXLGV([SHULPHQWDO FRQGLWLRQVDUHFULWLFDOLQWKHUXSWXUHWHQVLOHVWUHQJWKWHVW DQGWKHUHDUHVHYHUDOYDULDEOHVVDPSOHOD\HUK\GUDWLRQ WLPHRIK\GUDWLRQVDPSOHORDGWLPHRIORDGLQJGHWDFK PHQWUDWHHWFZKLFKVKRXOGEHRSWLPL]HGDQGVHWLQ RUGHUWRSURGXFHUHSURGXFLEOHUHVXOWV7KHUHSURGXFLELOLW\ RIUKHRORJLFDOPHDVXUHVLVUHDVRQDEO\JRRGVLQFHWKH PHDVXUHVDUHWDNHQRQDOUHDG\EDODQFHGPL[WXUHVFRP SRVLWLRQS+DQGWHPSHUDWXUHFDQEHFDUHIXOO\FRQWUROOHG DQGWKHUHIRUHIHZHUUHSHWLWLRQVDUHQHFHVVDU\WRREWDLQ VWDWLVWLFDOO\VLJQLFDQWGDWD7KXVLWFDQEHFRQFOXGHG WKDWERWKPHWKRGVFRQWULEXWHWRGLIIHUHQWH[WHQWVWRZDUG H[SODLQLQJWKHPXFRDGKHVLYHSKHQRPHQRQGHSHQGLQJ RQWKHPXFRDGKHVLRQPHFKDQLVPLQYROYHGV\VWHPW\SH SRO\PHUXVHGHWF0DWKLRZLW]&KLFNHULQJ/HKU +DJHUVWURP
Page 12
)&&DUYDOKR0/%UXVFKL5&(YDQJHOLVWD03'*UHPLmR Tests analyzing molecular interactions involved in mucoadhesion 7KHJHQHUDOSUREOHPDULVLQJIURPPHWKRGVWKDWVKRZ WKHDGKHVLRQIRUFHDQGIURPWKHUKHRORJLFDOPHWKRGVLVWKDW WKHPXFRDGKHVLYHUHVSRQVHLVVHHQPDFURVFRSLFDOO\ZKLOH WKHLQWHUDFWLRQVRFFXUDWDPLFURVFRSLFOHYHO 7KHXVHRIORZIUHTXHQF\GLHOHFWULFVSHFWURVFRS\ UHSUHVHQWVDQDWWHPSWWRVWXG\JHOPXFXVLQWHUDFWLRQVQHDU WKHPROHFXODUOHYHO,WHYDOXDWHVWKHSRVVLEOHSK\VLFRFKH PLFDOLQWHUDFWLRQVEHWZHHQPROHFXOHVDQGJO\FRSURWHLQV RIWKHPXFXVDWWKHLQWHUIDFHZKLFKLVFRQVLGHUHGWKH VWHSSUHFHGLQJWKHIRUPDWLRQRIERQGVGXULQJWKHPXFR DGKHVLRQSURFHVV7KLVWHFKQLTXHLQYROYHVWKHVWXG\RI PDWHULDOUHVSRQVHWRWKHDSSOLFDWLRQRIDQHOHFWULFDOHOG $VLQXVRLGDOYROWDJHLVDSSOLHGWKURXJKRXWWKHVDPSOHDQG WKHUHVSRQVHLVPHDVXUHGLQIXQFWLRQRIWKHIUHTXHQF\ )URPWKHUHVSRQVHVWKHLPSHGDQFHRUSHUPLWWLYLW\RIWKH VDPSOHLVREWDLQHGDQGWKHSURSHUW\RIFKDUJHVFKDQJLQJ LQWKHV\VWHPFDQEHGHWHUPLQHG+lJHUVWU|P7KLV WHFKQLTXHFDQSURYLGHLQIRUPDWLRQDERXWWKHFRPSDWLELOLW\ EHWZHHQPXFXVDQGPXFRDGKHVLYHV\VWHPE\PHDQVRIWKH HYDOXDWLRQRIWKHPRYHPHQWRIWKHFKDUJHGSDUWLFOHV7KLV FRPSDWLELOLW\LVDFKLHYHGDFFRUGLQJWRWKHHDVHZLWKZKLFK WKHSDUWLFOHFURVVHVWKHEDUULHUEHWZHHQWKHJHODQGPXFRXV PHPEUDQH7KHGLHOHFWULFPHDVXUHVUHYHDOLQIRUPDWLRQ DERXWWKHJHODQGWKHPXFRXVPHPEUDQHVHSDUDWHO\DQG DERXWWKHLQWHUIDFHEHWZHHQWKHP+lJHUVWU|P(GVPDQ 6WUPPH 6LQFHWKHPXFRDGKHVLRQSURFHVVFDQEHDFRQVH TXHQFHRILQWHUDFWLRQVEHWZHHQWKHPXFXVOD\HUDQGWKH PXFRDGKHVLYHSRO\PHULWLVKLJKO\GHSHQGHQWXSRQWKH PROHFXODUVWUXFWXUHLQFOXGLQJLWVFKDUJH,WLVDOVRZHOO NQRZQWKDWJO\FRSURWHLQVPROHFXOHVZKLFKIRUPWKH PXFXVVWUXFWXUHDUHQHJDWLYHDWSK\VLRORJLFDOS+%\ PHDQVRI]HWDSRWHQWLDOLWLVSRVVLEOHWRXQGHUVWDQGWKH SRO\PHUPXFLQHOHFWURVWDWLFLQWHUDFWLRQV7DNHXFKL HWDO 7KH]HWDSRWHQWLDORIGLVSHUVLRQLVGHQHGDVWKH SRWHQWLDOEHWZHHQWKHOLTXLGVXSHUFLDOOD\HUVXUURXQGLQJ WKHGLVSHUVHGSDUWLFOHDQGWKHUHPDLQLQJVROXWLRQYROXPH ,WLVDPHDVXUHRIWKHQHWVXUIDFHFKDUJHRISDUWLFOHVLQD GLVSHUVHGV\VWHP%RFDWDM HWDO ,QWKLVWHVWWKH PXFLQSDUWLFOHVDUHVXVSHQGHGLQDQDSSURSULDWHEXIIHUDQG PL[HGZLWKDVROXWLRQRIWKHSRO\PHU,IWKHDGGLWLRQRI WKHSRO\PHUFKDQJHVWKH]HWDSRWHQWLDOYDOXHRIWKHPXFLQ SDUWLFOHVWKLVFDQVXJJHVWJUHDWHUDIQLW\EHWZHHQSRO\PHU DQGPXFLQSDUWLFOHV7DNHXFKL HWDO $QRWKHUWHFKQLTXHEHLQJDSSOLHGWRHYDOXDWHPR OHFXODULQWHUDFWLRQVLVWKHRSWLFDOELRVHQVRURUUHVRQDQW PLUURUELRVHQVRUWHFKQLTXH6LJXUGVVRQ/RIWVVRQDQG /HKUXVHGWKLVWHFKQLTXHWRPHDVXUHWKHLQWHUDFWLRQ EHWZHHQJO\FRSURWHLQVRIWKHPXFXVDQGGLIIHUHQWSRO\ PHUV,WDOORZVWKHPRQLWRULQJRIDQ\LQWHUDFWLRQEHWZHHQ WZRXQNQRZQPROHFXOHVLQUHDOWLPHVLQFHRQHRIWKHP FDQEHLPPRELOL]HGZLWKFRYDOHQWRUQRQFRYDOHQWRQWKH V\VWHPVXUIDFHZKLOHWKHRWKHUUHPDLQVLQVROXWLRQDWWKH VXUIDFH7KHPROHFXOHVLQVROXWLRQZKHQELQGLQJWRWKH LPPRELOL]HGPROHFXOHVDOWHUWKHUHIUDFWLRQLQGH[RIWKH PHGLXPDQGWKLVFKDQJHLVGHWHFWHGE\WKHVFUHHQLQJRID ODVHUEHDP7KHUHVXOWVRIWKLVVWXG\VXJJHVWHGWKHQHHGIRU DFOHDUHUGHQLWLRQRIPXFRDGKHVLRQEHFDXVHWKH\FDOOHG LQWRTXHVWLRQWKHSRO\PHUVWKDWDUHVZHOOLQJGHSHQGHQW DQGXQGHUJR LQVLWX JHOLFDWLRQEHFDXVHWKH\GRQRWVHHP WRLQWHUDFWZLWKJO\FRSURWHLQVDOWKRXJKWKH\DUHFDOOHG PXFRDGKHVLYHV6LJXUGVVRQ/RIWVVRQ/HKU $QRWKHUWHVWXVLQJWKHVDPHSULQFLSOHWKH%LDFRUHWHVW ZDVDSSOLHGIRUWKHDQDO\VLVRIPXFRDGKHVLRQE\7DNHXFKL HWDO 7KLVWHVWLVEDVHGRQWKHSDVVDJHRIDPXFLQ VXVSHQVLRQWKURXJKDVHQVRUFRQWDLQLQJWKHLPPRELOL]HG SRO\PHU:KHQDPXFLQSDUWLFOHELQGVWRWKHSRO\PHUDW WKHVHQVRUERWKWKHVROXWHFRQFHQWUDWLRQDQGWKHUHIUDFWLRQ LQGH[RQWKLVVXUIDFHXQGHUJRFKDQJHVZKHUHWKHLQWHUDFWLRQ LVTXDQWLWDWLYHO\HYDOXDWHGDQGUHSURGXFHGRQDGLDJUDP 7KHVHQVRULVDFKLSZLWKDJODVVVXUIDFHFRYHUHGLQDQH JROGOD\HUZKHUHIXQFWLRQDOJURXSVDUHLQWURGXFHGDQGWKH SRO\PHULVDWWDFKHG7DNHXFKL HWDO Imaging methods 2SWLFDOPLFURVFRSHVRIIHULQVXIFLHQWUHVROXWLRQ IRUVWXG\LQJHIIHFWVDWDPROHFXODUOHYHO)RUVXFKLQYHV WLJDWLRQVDUHVROXWLRQDWPLFURRUQDQRPHWULFOHYHOLV QHHGHG(OHFWURQLFPLFURVFRS\JLYHVDODUJHUYLHZEXW WKHHQYLURQPHQWDOFRQGLWLRQVLQZKLFKWKHVDPSOHPXVWEH VXEPLWWHGDUHIDUIURPWKHSK\VLRORJLFDOFRQGLWLRQV)RU LQVWDQFHWKHVDPSOHVDUHDQDO\]HGLQDYDFXXPFKDPEHU DQGJHQHUDOO\DUHFRYHUHGZLWKDPHWDOOLFOPWRDYRLG FKDQJHVFDXVHGE\WKHHOHFWURQLFUD\V0DWKLRZLW]&KL FNHULQJ/HKU $WRPLFIRUFHPLFURVFRS\$)0LVDUHODWLYHO\QHZ WHFKQLTXHWKDWRYHUFRPHVVXFKUHVWULFWLRQVEHFDXVHLWFDQ EHXVHGXQGHUDQ\HQYLURQPHQWDOFRQGLWLRQVLQDLUOLTXLGV RUYDFXXP,WHQODUJHVPRUHWKDQ IROGZKLFKHQDEOHV YLVXDOL]DWLRQRILVRODWHGDWRPVDQGRIIHUVDWULGLPHQVLRQDO LPDJHRIWKHVXUIDFH7KHHTXLSPHQW)LJXUHOHIWVLGH KDVDVXSSRUWFRPELQHGZLWKDSUREHSHUSHQGLFXODUO\DW WDFKHGWRLW7KLVWLSPRYHVWRZDUGDSODQHSDUDOOHOWRWKH VDPSOHDFTXLULQJLWVWRSRJUDSKLFFKDUDFWHULVWLFVDQGWKH WLSSRVLWLRQLVUHFRUGHGE\DQRSWLFGHHFWLRQV\VWHPD ODVHUEHDPLVUHHFWHGRQWRWKHVXSSRUWDQGLWVSRVLWLRQLV WKHQIXUWKHUUHHFWHGE\DPLUURUUHDFKLQJDSKRWRGLRGH VHQVRU$IRUFHGLVWDQFHFXUYHLVSORWWHGWRPHDVXUHWKH
Page 13
0XFRDGKHVLYHGUXJGHOLYHU\V\VWHPV IRUFHVEHWZHHQWKLVWLSDQGWKHVXUIDFHRILQWHUHVW0DWKLR ZLW]&KLFNHULQJ/HKU7KLVFXUYHLVWKHQXVHGLQ ELRDGKHVLRQVWXGLHV7KLVHQWDLOVFRDWLQJWKHWLSLQDGKHVLYH PDWHULDOZKLFKLVJHQHUDOO\VSKHULFDOLQVKDSH)LJXUH ULJKWVLGHDQGWKHQWKHLQWHUDFWLRQZLWKWKHVXUIDFHLQWKLV FDVHWKHPXFRXVPHPEUDQHFDQEHPHDVXUHG&OHDU\ %URPEHUJ0DJQHU %HVLGHV$)0WKHUHDUHRWKHUWHFKQLTXHVXVLQJ SKRWRJUDSKLFLPDJHVVXFKDVXRUHVFHQFHPLFURVFRS\ DQGFRQIRFDOODVHUVFDQQLQJPLFURVFRS\&6/05HVXOWV DFKLHYHGLQ H[YLYR WHVWVOLNHWKHQRQHYHUWHGJXWVDFWHVW .HHO\ HWDO FDQEHEHWWHUYLVXDOL]HGZLWKWKLV WHFKQLTXH8VLQJUDGLRLVRWRSHVRUUDGLRDFWLYHPDUNHUV LWLVSRVVLEOHWRWUDFHWKHSRO\PHURUWKHVXEVWDQFHWREH LQFRUSRUDWHGLQWRWKHUHOHDVHV\VWHPZKHUHWKHLUORFDWLRQ LVYLVXDOL]HGRQWKHVSHFLFPLFURVFRSHDIWHUWKHH[FLVLRQ RIWKHPHPEUDQH7DNHXFKL HWDO XVHG&6/0WR DQDO\]HOLSRVRPHVIRUPXODWHGZLWKDXRUHVFHQWWUDFHUDQG DGPLQLVWHUHGE\WKHRUDOURXWHLQUDWV7KHLQWHVWLQHVZHUH UHPRYHGDWDQDSSURSULDWHWLPHDIWHUDGPLQLVWUDWLRQDQG WKHUHWHQWLRQRIWKHIRUPXODWLRQZDVYHULHGWKURXJKWKH LPDJHVDFKLHYHGRQWKHFRQIRFDOPLFURVFRSH ,QWKHVSHFLFFDVHRIELRDGKHVLYHPLFURVSKHUHV WKHJUHDWHUGLIFXOW\LQWKHLUGHYHORSPHQWLVWKHVHQVL WLYHTXDQWLFDWLRQRIWKHELRDGKHVLYHLQWHUDFWLRQVXQGHU SK\VLRORJLFDOFRQGLWLRQV6HYHUDOWHFKQLTXHVDUHEHLQJ GHYHORSHGWRPHDVXUHWKHDGKHVLRQRIJUHDWYROXPHVLQ WKLVNLQGRIVDPSOHDQGRWKHUVWRRIIHUPRUHTXDOLWDWLYH GDWD7KHSUHYLRXVO\GHVFULEHGPLFURIRUFHEDODQFHPH WKRGRORJ\ZDVDQDWWHPSWWRFLUFXPYHQWWKLVGLIFXOW\,Q SDUDOOHODQRWKHUWHFKQRORJ\ZDVGHYHORSHG(OHFWURPDJ QHWLF)RUFHWUDQVGXFWLRQ()7,QDGGLWLRQWRLQIRUPDWLRQ DERXWELRDGKHVLYHIRUFHVWKLVWHFKQRORJ\DOVRRIIHUVWKH VLPXOWDQHRXVYLGHRLPDJHRIWKHLQWHUDFWLRQVZLWKKLJK UHVROXWLRQDQGXQGHUSK\VLRORJLFDOFRQGLWLRQV)LJXUH FIGURE 12 &RQVWLWXHQWVRI$)0DQGWKHDGDSWDWLRQVPDGH IRUPHDVXULQJWKHDGKHVLYHIRUFHEHWZHHQSRO\PHUDQGPXFXV VXUIDFH$GDSWHGIURP&OHDU\%URPEHUJDQG0DJQHU 0DWKLRZLW]&KLFNHULQJDQG/HKU VFKHPDWLFDOO\LOOXVWUDWHVWKHWHFKQLTXH7KHPXFRXV PHPEUDQHLVPRXQWHGLQDFRPSDUWPHQWXQGHUSK\VLROR JLFDOFRQGLWLRQVDQGWKHPLFURVSKHUHLVSRVLWLRQHGGLUHFWO\ EHORZWKHPDJQHWLFSUREH7KHFRPSDUWPHQWLVVORZO\ PRYHGGRZQLQDQRSSRVLWHGLUHFWLRQWRWKHSUREHDQG WKHYLGHRFDPHUDLVXVHGWRGHWHFWVSKHUHPRYHPHQW $FFRUGLQJWRWKHPRYHPHQWWKHFRQWUROV\VWHPLQFUHDVHV WKHPDJQHWLFFXUUHQWDQGWKHUHVXOWLQJPDJQHWLFIRUFH SXOOVWKHVSKHUHWRLWVLQLWLDOSRVLWLRQVHSDUDWLQJLWIURP WKHWLVVXH$IWHUWKHH[SHULPHQWWKHPDJQHWLFFXUUHQWLV FRQYHUWHGLQWRIRUFHDQGWKHFRPSXWHUFDOFXODWHVWKHSDUD PHWHUVRIDGKHVLRQ7KHPXFRXVPHPEUDQHWREHDQDO\]HG FDQEHDWWDLQHGDIWHUDQH[SHULPHQWXVLQJDQHYHUWHGJXW VDF0DWKLRZLW]&KLFNHULQJ/HKU $QDOWHUQDWLYHWHFKQLTXHZKLFKDOVRXVHVDYLGHR FDPHUDLVWKHRZFKDQQHOPHWKRG$QHJODVVFKDQQHOLV OOHGZLWKDQDTXHRXVERYLQHVXEPD[LOODU\PXFLQVROXWLRQ PDLQWDLQHGDW &DQGKXPLGDLULVSDVVHGWKURXJKWKH FKDQQHO$SDUWLFOHRIWKHELRDGKHVLYHSRO\PHULVSODFHGLQ WKHPXFLQJHODQGERWKWKHVWDWLFDQGG\QDPLFEHKDYLRUV DUHPRQLWRUHGE\WKHFDPHUDDWIUHTXHQWWLPHLQWHUYDOV $KXMD.KDU$OL Falling Liquid Film Method 1LHOVHQ6FKXEHUWDQG+DQVHQXVHGDPH WKRGSURSRVHGE\5DQJR5DRDQG%XULLQZKLFK WKHFKRVHQPXFRXVPHPEUDQHLVSODFHGLQDVWDLQOHVV VWHHOF\OLQGULFDOWXEHZKLFKKDVEHHQORQJLWXGLQDOO\FXW 7KLVVXSSRUWLVSODFHGLQFOLQHGLQDF\OLQGULFDOFHOOZLWK DWHPSHUDWXUHFRQWUROOHGDW &$QLVRWRQLFVROXWLRQLV SXPSHGWKURXJKWKHPXFRXVPHPEUDQHDQGFROOHFWHGLQD EHDNHU)LJXUH6XEVHTXHQWO\LQWKHFDVHRISDUWLFXODWH V\VWHPVWKHDPRXQWUHPDLQLQJRQWKHPXFRXVPHPEUDQH FDQEHFRXQWHGZLWKWKHDLGRIDFRXOWHUFRXQWHU&KRZGD U\5DR)RUVHPLVROLGV\VWHPVWKHQRQDGKHUHG FIGURE 13 (OHPHQWVRI()7$GDSWHGIURP0DWKLRZLW] &KLFNHULQJDQG/HKU
Page 14
)&&DUYDOKR0/%UXVFKL5&(YDQJHOLVWD03'*UHPLmR PXFRDGKHVLYHFDQEHTXDQWLILHGE\KLJKSHUIRUPDQFH OLTXLGFKURPDWRJUDSK\1LHOVHQ6FKXEHUW+DQVHQ ,QWKLVODWHUFDVHSRUFLQHVWRPDFKLQWHVWLQDODQGEXFFDO PXFXVZHUHWHVWHGDQGDOVRMHMXQXPIURPUDEELWV7KH YDOLGDWLRQRIWKLVPHWKRGVKRZHGWKDWWKHW\SHRIPXFXV XVHGGRHVQRWLQXHQFHWKHUHVXOWV7KHUHOHDVHV\VWHPV WHVWHGZHUHSUHFXUVRUVRIOLTXLGFU\VWDOVFRQVWLWXWHGE\ PRQRJO\FHULGHV7KLVPHWKRGRORJ\DOORZVWKHYLVXDOL ]DWLRQRIIRUPDWLRQRIOLTXLGFU\VWDOOLQHPHVRSKDVHRQ WKHPXFRXVPHPEUDQHDIWHUWKHRZLQJRIWKHXLGVDQG WKURXJKDQDO\VLVE\PHDQVRISRODUL]HGOLJKWPLFURVFRS\ 1LHOVHQ6FKXEHUW+DQVHQ In vivo tests 7KHUHLVVFDQWLQIRUPDWLRQDYDLODEOHRQWKH LQYLYR EHKDYLRURIPXFRDGKHVLYHIRUPXODWLRQVHVSHFLDOO\LQ KXPDQV6lNNLQHQ HWDO DSSOLHGJDPPDVFLQWLJUD SK\WRDQDO\]HPXFRDGKHVLRQ LQYLYR RIFKLWRVDQZLWKLQ WKHJDVWURLQWHVWLQDOWUDFW*DPPDVFLQWLJUDSK\DOORZVWKH LPPHGLDWHYLVXDOL]DWLRQRIDOOWKHIRUPXODWLRQWUDQVLW ZLWKORZH[SRVXUHRIWKHVXEMHFWVWRUDGLDWLRQ7KHVWXG\ HPSKDVL]HGWKHLPSRUWDQFHRI LQYLYR VWXGLHVEHFDXVH DOWKRXJKFKLWRVDQH[KLELWVDQRXWVWDQGLQJPXFRDGKHVLRQ FDSDFLW\ LQYLWUR WKHUHWHQWLRQWLPHDWWKHDEVRUSWLRQVLWH LQWKHKXPDQJDVWURLQWHVWLQDOWUDFWZDVUHODWLYHO\VKRUWDQG QRWVXIFLHQWO\UHSURGXFLEOH6lNNLQHQ HWDO 7KH JDVWURLQWHVWLQDOWUDQVLWWLPHLQDQLPDOVFDQDOVREHHYDOX DWHGLQDQRQLQYDVLYHZD\LQZKLFKWKHUHOHDVHV\VWHPV FDQEHIRUPXODWHGZLWKRSDTXHUDGLRLVRWRSHVDQGVLJQDOV FDQEHIROORZHGE\;UD\VZLWKRXWDIIHFWLQJQRUPDOJDV WURLQWHVWLQDOPRWLOLW\&KRZGDU\5DR 7KHQXPEHURIPHWKRGRORJLHVDSSOLHGWRDQDO\]H PXFRDGKHVLRQLVFRQVWDQWO\JURZLQJDOWKRXJKWKHXVH RIGLIIHUHQWPHWKRGVPD\VRPHWLPHVOHDGWRLQFRKHUHQFH DPRQJUHVXOWVGXHWRWKHKHWHURJHQHLW\RISDUDPHWHUVDQG FRQGLWLRQVXVHG6LJXUGVVR/RIWVVRQ/HKU$KXMD HWDO H[DPLQHGYDULRXVVWXGLHVWKDWXVHGWKHWHQVLRQ UHVLVWDQFHPHWKRGDQGHDFKKDGHPSOR\HGGLIIHUHQWPRGHOV RIPXFRXVPHPEUDQHDQGHTXLSPHQW'HVSLWHWKHODUJH ERG\RIHYLGHQFHREWDLQHGWRGDWHIXUWKHULQYHVWLJDWLRQV DLPHGDWVWDQGDUGL]LQJWKHPHWKRGRORJLHVDUHZDUUDQWHG CONCLUSIONS 6WXGLHVRQPXFRDGKHVLYHV\VWHPVKDYHIRFXVHGRQ DEURDGDUUD\RIDVSHFWV,WLVDJURZWKDUHDZKRVHJRDOLV WKHGHYHORSPHQWRIQHZGHYLFHVDQGPRUHLQWHOOLJHQW SRO\PHUVDVZHOODVWKHFUHDWLRQRIQHZPHWKRGRORJLHV WKDWFDQEHWWHUHOXFLGDWHWKHPXFRDGKHVLRQSKHQRPHQRQ :LWKWKHJUHDWLQX[RIQHZPROHFXOHVVWHPPLQJIURP GUXJUHVHDUFKPXFRDGKHVLYHV\VWHPVPD\SOD\DQLQFUH DVLQJUROHLQWKHGHYHORSPHQWRIQHZSKDUPDFHXWLFDOV ACKNOWLEDGEMENTS 7KHDXWKRUVZLVKWRWKDQN&$3(6&RRUGHQDomR GH$SHUIHLoRDPHQWRGH3HVVRDOGH1tYHO6XSHULRUIRU QDQFLDOVXSSRUW REFERENCES $+8-$$.+$55.$/,-0XFRDGKHVLYHGUXJGHOLYHU\ V\VWHPV 'UXJ'HY,QG3KDUP YQS $1'5(:6*3-21(6'65KHRORJLFDOFKDUDFWHUL]DWLRQ RIELRDGKHVLYHELQDU\SRO\PHULFV\VWHPVGHVLJQHGDV SODWIRUPVIRUGUXJGHOLYHU\LPSODQWV %LRPDFURPRO Y S $1'5(:6*3/$9(57<73-21(6'60XFRDGKHVLYH SRO\PHULFSODWIRUPVIRUFRQWUROOHGGUXJGHOLYHU\ (XU- 3KDUP%LRSKDUP YQS %2&$7$-0929.7.(5(&0',01,.$' *5$%1$5,05+$5$7KHFRUUHODWLRQEHWZHHQ]HWD SRWHQWLDODQGPXFRDGKHVLRQVWUHQJWKRQSLJYHVLFDOPXFRVD %LRO3KDUP%XOOY QS %5$922681$,9$87+,(5&)$5$%2//,1, $3$/0,(5,*)321&+(/*0XFRDGKHVLRQ PHFKDQLVPRIFKLWRVDQDQGWKLRODWHGFKLWRVDQSRO\LVREXWL\O F\DQRDFU\ODWHFRUHVKHOOQDQRSDUWLFOHV %LRPDWHULDOV Y QS FIGURE 14 6FKHPDWLFUHSUHVHQWDWLRQRI LQYLWUR PRGHOXVHG E\1LHOVHQ6FKXEHUWDQG+DQVHQDGDSWHGIURP5DQJR 5DRDQG%XUL
Page 15
0XFRDGKHVLYHGUXJGHOLYHU\V\VWHPV %520%(5*/7(0&+(1.20$/$.+299 +$77217$%LRDGKHVLYHSURSHUWLHVDQGUKHRORJ\RI SRO\HWKHUPRGLILHGSRO\DFU\OLFDFLGK\GURJHOV ,QW- 3KDUP YQS %586&+,0/ 'HVHQYROYLPHQWRHFDUDFWHUL]DomRGHVLVWHPDV GHOLEHUDomRGHSUySROLVLQWUDEROVDSHULRGRQWDO 5LEHLUmR 3UHWRS>7HVHGH'RXWRUDGR)DFXOGDGHGH &LrQFLDV)DUPDFrXWLFDVGH5LEHLUmR3UHWR8QLYHUVLGDGH GHVmR3DXOR@ %586&+,0/)5(,7$622UDOELRDGKHVLYHGUXJGHOLYHU\ V\VWHPV 'UXJ,QG3KDUP YQS %586&+,0/-21(6'63$1=(5,+*5(0,2 03')5(,7$62/$5$(+*6HPLVROLGV\VWHPV FRQWDLQLQJSURSROLVIRUWKHWUHDWPHQWRISHULRGRQWDOGLVHDVH LQYLWURUHOHDVHNLQHWLFVV\ULQJHDELOLW\UKHRORJLFDOWH[WXUDO DQGPXFRDGKHVLYHSURSHUWLHV -3KDUP6FL YQ S %586&+,0/-21(6'63$1=(5,+*5(0,2 03')5(,7$62/$5$(+*'HYHORSPHQWDQG FKDUDFWHUL]DWLRQRISUHFXUVRURIOLTXLGFU\VWDOOLQHSKDVHZLWK SURSROLVFRQWDLQLQJPLFURSDUWLFOHVIRUXVHLQWKHWUHDWPHQW RISHULRGRQWDOGLVHDVH 'UXJ'HYHORS,QG3KDUP Y QS &$//(16&&(8/(0$16-/8':,*$)25(0$1 35(021-35KHRORJLFDOVWXG\RQPXFRDGKHVLYLW\RI VRPHQDVDOSRZGHUIRUPXODWLRQV (XU- 3KDUP%LRSKDUP YQS &(8/(0$16-9,1&.,(5,/8':,*$7KHXVH RI[DQWDQJXPLQDQRSKWKDOPLFOLTXLGGRVDJHIRUP UKHRORJLFDOFKDUDFWHUL]DWLRQRIWKHLQWHUDFWLRQZLWKPXFLQ -3KDUP6FL YQS &+2:'$5<&355$2<60XFRDGKHVLYHPLFURVSKHUHV IRUFRQWUROOHGGUXJGHOLYHU\ %LRO3KDUP%XOO YQ S &/($5<-%520%(5*/0$*1(5($GKHVLRQRI 3RO\HWKHU0RGLHG3RO\DFU\OLFDFLGWR0XFLQ /DQJPXLU YQS (9$1*(/,67$5& 6LVWHPDVGHOLEHUDomRFRQWURODGDGH IiUPDFRV $UDUDTXDUD I>7HVHGH/LYUH'RFrQFLD HP)DUPDFRWpFQLFD)DFXOGDGHGH&LrQFLDV)DUPDFrXWLFDV 8QLYHUVLGDGH(VWDGXDO3DXOLVWD-~OLRGH0HVTXLWD)LOKR@ )250$5,=7385%$10&&6,/9$-81,25$$ *5(0,203'2/,9(,5$$*0LFURHPXOV}HV HIDVHVOtTXLGDVFULVWDOLQDVFRPRVLVWHPDVGHOLEHUDomRGH IiUPDFRV 5HY%UDV&LrQF)DUP YQS *2727025,6+,7$0.$9,0$1'$11- 7$.$<$0$.3(33$61$*DVWURLQWHVWLQDO WUDQVLWDQGPXFRDGKHVLYHFKDUDFWHULVWLFVRIFRPSOH[DWLRQ K\GURJHOVLQUDWV -3KDUP6FL YQS *5$%29$&9*8**,'%(51.236&+1h5&+ $&RPSDULVRQRIWKHPXFRDGKHVLYHSURSHUWLHVRIYDULRV SRO\PHUV $GY'UXJ'HO5HY YQS +b*(5675g0+ 3RO\PHUJHOVDVSKDUPDFHXWLFDOGRVDJH IRUPV UKHRORJLFDOSHUIRUPDQFHDQGSK\VLFRFKHPLFDO LQWHUDFWLRQVDWWKHJHOPXFXVLQWHUIDFHIRUIRUPXODWLRQV LQWHQGHGIRUPXFRVDOGUXJGHOLYHU\ 8SSVDOD I>'LVVHUWDWLRQIRUWKHGHJUHHRI'RFWRURI3KLORVRSK\LQ 3KDUPDFHXWLFV8SSVDOD8QLYHUVLW\@ +b*(5675g0+('60$1.67500(0/RZ )UHTXHQF\'LHOHFWULF6SHFWURVFRS\DVD7RROIRU6WXG\LQJ WKH&RPSDWLELOLW\EHWZHHQ3KDUPDFHXWLFDO*HOVDQG0XFXV 7LVVXH -3KDUP6FL YQS +$66$1((*$//2-0$VLPSOHUKHRORJLFDOPHWKRGIRU WKH LQYLWUR DVVHVVPHQWRIPXFLQSRO\PHUELRDGKHVLYHERQG VWUHQJWK 3KDUP5HV YQS +8$1*</(2%$1'81*:)266$3(33$61 $0ROHFXODUDVSHFWVRIPXFRDQGELRDGKHVLRQ7HWKHUHV VWUXFWXUHVDQGVLWHVSHFLFVXUIDFHV -&RQWURO5HOHDVH YQS -81*,1*(5+(7+$12809(5+2()-&'UXJ 'HOLYHU\0XFRDGKHVLYH+\GURJHOV (QF\FORSHGLDRI 3KDUPDFHXWLFDO7HFKQRORJ\ HG$YDLODEOHDWKWWS ZZZLQIRUPDZRUOGFRPVPSSFRQWHQWaGE DOOaFRQWHQW D aWDE FRQWHQ!$FFHVVHGRQRXW .((/<658//$<$:,/621&&$50,&+$(/$ &$55,1*7216&25),(/'$+$''/(721' 0%5$<'(1'- ,QYLWUR DQG H[YLYR LQWHVWLQDOWLVVXH PRGHOVWRPHDVXUHPXFRDGKHVLRQRISRO\PHWKDFU\ODWH DQG1WULPHWK\ODWHGFKLWRVDQSRO\PHUV 3KDUP5HV Y QS
Page 16
)&&DUYDOKR0/%UXVFKL5&(YDQJHOLVWD03'*UHPLmR .2&.,6&+65((6*'<281*6$76,%28./,6 -60$57-'$GLUHFWVWDLQLQJPHWKRGWRHYDOXDWHWKH PXFRDGKHVLRQRISRO\PHUVIURPDTXHRXVGLVSHUVLRQ - &RQWURO5HOHDVH YQS /((-:3$5.-+52%,1621-5%LRDGKHVLYHEDVHG GRVDJHIRUPV7KHQH[WJHQHUDWLRQ -3KDUP6FL YQ S /(+5&0/HFWLQPHGLDWHGGUXJGHOLYHU\7KHVHFRQG JHQHUDWLRQRIELRDGKHVLYHV -&RQWURO5HOHDVH YQ S /(81*6+652%,1621-53RO\PHUVWUXFWXUHIHDWXUHV FRQWULEXWLQJWRPXFRDGKHVLRQ,, -&RQWURO5HOHDVH Y QS 0$/067(10 6XUIDFWDQWVDQGSRO\PHUVLQGUXJGHOLYHU\ 'UXJVDQGWKHSKDUPDFHXWLFDO6FLHQFHV1HZ 'HNNHUS 0$7+,2:,7=(&+,&.(5,1*'(/(+5&0 (GV%LRDGKHVLYHGUXJGHOLYHU\V\VWHPVIXQGDPHQWDOV QRYHODSSURDFKHVDQGGHYHORSPHQW 'UXJVDQGWKH 3KDUPDFHXWLFDO6FLHQFHV 1HZ S 0257$=$9,6$02*+,0,+5(IIHFWRI6XUIDFWDQW 7\SHDQG&RQFHQWUDWLRQRQWKH'XUDWLRQRI0XFRDGKHVLRQ RI&DUERSRODQG+30&6ROLG&RPSDFWV ,U-3KDUP 5HV YQS 1$*$,7$GKHVLYHWRSLFDOGUXJGHOLYHU\V\VWHP -&RQWURO 5HOHDVH YSS 1$*$,71,6+,0272<1$0%8168=8.,< 6(.,1(.3RZGHUGRVDJHIRUPRILQVXOLQIRUQDVDO DGPLQLVWUDWLRQ -&RQWURO5HOHDVH YQS 1,(/6(1/66&+8%(57/+$16(1-%LRDGKHVLYH GUXJGHOLYHU\V\VWHPV,&KDUDFWHUL]DWLRQRIPXFRDGKHVLYH SURSHUWLHVRIV\VWHPVEDVHGRQJO\FHU\OPRQRROHDWHDQG JO\FHU\OPRQROLQROHDWH (XU-3KDUP6FL YQS 3$5.-62+<.-81*+<.,0-0.,0& . ,QVLWX JHOOLQJDQGPXFRDGKHVLYHSRO\PHUYHKLFOHVIRU FRQWUROOHGLQWUDQDVDOGHOLYHU\RISODVPLG'1$ -%LRPHG 0DVWHU5HV YQS 3(33$61$+8$1*<1DQRVFDOHWHFKQRORJ\RI PXFRDGKHVLYHLQWHUDFWLRQV $GY'UXJ'HO5HY YQ S 3(33$61$6$+/,1--+\GURJHOVDVPXFRDGKHVLYHDQG ELRDGKHVLYHPDWHULDOVDUHYLHZ %LRPDWHULDOV YQ S 4,8<3$5..(QYLURQPHQWVHQVLWLYHK\GURJHOVIRUGUXJ GHOLYHU\ $GY'UXJ'HO5HY YQS 5$1*25$2.9%85,3 $QRYHO LQVLWX PHWKRGWRWHVW SRO\PHUVDQGFRDWHGPLFURSDUWLFOHVIRUELRDGKHVLRQ ,QW- 3KDUP YQS 6b..,1(100$592/$-.$1(59$+ /,1'(9$//.0$577,0$592/$$$$UH FKLWRVDQIRUPXODWLRQVPXFRDGKHVLYHLQWKHKXPDQVPDOO LQWHVWLQH"$QHYDOXDWLRQEDVHGRQJDPPDVFLQWLJUDSK\ ,QW -3KDUP YYQS 6$1726&$-$&2%-6+(57=2*%$)5((60$1 %'35(66'/+$513,&+$51&+$,3 0$7+,2:,7=(&RUUHODWLRQRIWZRELRDGKHVLRQDVVD\V WKHHYHUWHGVDFWHFKQLTXHDQGWKH&$+1PLFUREDODQFH - &RQWURO5HO YQS 6+,16&/((-:<$1*.+/((&+3UHSDUDWLRQ DQGHYDOXDWLRQRIELRDGKHVLYHEHQ]RFDLQHJHOVIRUHQKDQFHG ORFDODQHVWKHWLFHIIHFWV ,QW-3KDUP YQS 6,*85'6621++/2)766217/(+5&0 $VVHVVPHQWRIPXFRDGKHVLRQE\DUHVRQDQWPLUURU ELRVHQVRU ,QW-3KDUP YQS 60$57-'7KHEDVLFVDQGXQGHUO\LQJPHFKDQLVPVRI PXFRDGKHVLRQ $GY'UXJ'HO5HY YQS 7$.(8&+,+7+21*%25,687(-0$768,< 68*,+$5$+<$0$0272++.$0$6+,0$ <1RYHOPXFRDGKHVLRQWHVWVIRUSRO\PHUVDQGSRO\PHU FRDWHGSDUWLFOHVWRGHVLJQRSWLPDOPXFRDGKHVLYHGUXJ GHOLYHU\V\VWHPV $GY'UXJ'HO5HY YQS 9<$67.%$%%$5$.6+$50$5.6,1*+ 60,65$$3UHOLPLQDU\EUDLQWDUJHWLQJVWXGLHVRQ LQWUDQDVDOPXFRDGKHVLYHPLFURHPXOVLRQRIVXPDWULSWDQ $$363KDUP6FL7HFK YQS((
Page 17
0XFRDGKHVLYHGUXJGHOLYHU\V\VWHPV :,6('/ +DQGERRNRISKDUPDFHXWLFDOFRQWUROOHGUHOHDVH WHFKQRORJ\ 1HZ :,77$<$$5((.8/6.58(1$7(-35$+6$51 &3UHSDUDWLRQDQGLQYLWURHYDOXDWLRQRIPXFRDGKHVLYH SURSHUWLHVRIDOJLQDWHFKLWRVDQPLFURSDUWLFOHVFRQWDLQLQJ SUHGQLVRORQH ,QW-3KDUP YQS :21*&)<8(1.+3(+..$QLQYLWURPHWKRG IRUEXFFDODGKHVLRQVWXGLHVLPSRUWDQFHRILQVWUXPHQW YDULDEOHV ,QW-3KDUP YQS :22'/(<-%LRDGKHVLRQQHZSRVVLELOLWLHVIRUGUXJ DGPLQLVWUDWLRQ" &OLQ3KDUPDFRNLQHW YQS 5HFHLYHGIRUSXEOLFDWLRQRQ WK $SULO $FFHSWHGIRUSXEOLFDWLRQRQ WK -XQH

About DocSlides
DocSlides allows users to easily upload and share presentations, PDF documents, and images.Share your documents with the world , watch,share and upload any time you want. How can you benefit from using DocSlides? DocSlides consists documents from individuals and organizations on topics ranging from technology and business to travel, health, and education. Find and search for what interests you, and learn from people and more. You can also download DocSlides to read or reference later.