Thesisvoorstellen opleiding Farmaceutische Wetenschappen Academiejaar 2008-2009 Dienst FABI
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Transcript of Thesisvoorstellen opleiding Farmaceutische Wetenschappen Academiejaar 2008-2009 Dienst FABI
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Thesisvoorstellenopleiding Farmaceutische WetenschappenAcademiejaar 2008-2009Dienst FABIProf. J. Smeyers-Verbeke Prof. Y. Vander HeydenProf. J. Plaizier-Vercammen
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Vakgroep Analytische Scheikunde en Farmaceutische Technologie
Prof. J. Smeyers-VerbekeProf. Y. Vander Heyden
Prof. J. Plaizier-Vercammen
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Vakgroep Analytische Scheikunde en Farmaceutische TechnologieWat doen wij?
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Vakgroep Analytische Scheikunde en Farmaceutische TechnologieDoel onderzoek: Evaluatie van nieuwemethodologien in scheidingstechnieken Methodeontwikkeling en -optimalisatieTechnieken: HPLC, CE, capillaire electrochromatografieToepassingen: Chirale scheidingen, snelle scheidingen, fingerprinting, geneesmiddelenanalyseExperimenteel design Data evaluatie- Voorspellen membraanpassage van geneesmiddelen- Voorspellen van anti-oxiderende eigenschappen van plantenextracten
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Thesisvoorstel professor Plaizier-Vercammen
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Capillaire ElectrochromatografieIndiana Tanret
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Technieken verbeteren?HPLCMiniaturisatie CLC: capillair
CEMeer affiniteit door toevoegen van stationaire fase
CEC combinatie HPLC + CE
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CEC: toestelSF in capillaire kolom: monolietenJe leert hoemonolietengemaakt worden
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Polymere monolietenBMABMAMETA +BMAMETA +BMAMETA +BMAEDMAEDMA
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Polymere monolietenBMABMAMETA +BMAMETA +BMAMETA +BMAEDMAEDMAPFSPFSPFSEDMABMAMETA +BMAPFSEDMA Poreus medium
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Doel thesisApplicatie-ontwikkeling
Transfereren van een bestaande HPLC-applicatie naar (p-)CECofOntwikkelen van een farmaceutische applicatie op een monolitische SF in p-CEC en/of CEC
Je ontwikkelt een strategie, voert ze uit en je verwerkt je resultaten
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Doel thesisHPLCCECVoordelen: efficientie? selectiviteit? resolutie?snellere runs?...
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Experimenteel design in methode optimalisatieBieke Dejaegher
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Experimenteel designExperimenteel design set-up waarbij de onderzochte factoren tegelijkertijd gevarierd worden factoren n voor n variren
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Experimenteel designExperimenteel design set-up waarbij de onderzochte factoren tegelijkertijd gevarierd worden factoren n voor n variren
In optimalisatie screening factoren met grootste invloed of effect op de onderzochte respons(en) bepalen belangrijkste factoren verder onderzoeken mbv response surface designsModelleren van de respons als functie van de factorenVoorbeelden: three-level full factorial designs, central composite designs, Box-Behnken designs, Doehlert designs, uniform designs
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DoelVerschillende response surface designs in optimalisatie vergelijken, welke meest geschikt?
3 factoren verschillend aantal experimenten !
Three-level full factorial designs: 33=27 exp.
Central composite designs: 23+6+min1= min 15 exp.
Box-Behnken designs: 13 exp.
Doehlert designs: 13 exp.
Uniform designs: 6 exp.
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DoelVerschillende response surface designs in optimalisatie vergelijken, welke meest geschikt?
3 factoren verschillend aantal experimenten !
Three-level full factorial designs: 33=27 exp.
Central composite designs: 23+6+min1= min 15 exp.
Box-Behnken designs: 13 exp.
Doehlert designs: 13 exp.
Uniform designs: 6 exp.
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DoelVerschillende response surface designs in optimalisatie vergelijken, welke meest geschikt?
3 factoren verschillend aantal experimenten !
Three-level full factorial designs: 33=27 exp.
Central composite designs: 23+6+min1= min 15 exp.
Box-Behnken designs: 13 exp.
Doehlert designs: 13 exp.
Uniform designs: 6 exp.
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DoelVerschillende response surface designs in optimalisatie vergelijken, welke meest geschikt?
3 factoren verschillend aantal experimenten !
Three-level full factorial designs: 33=27 exp.
Central composite designs: 23+6+min1= min 15 exp.
Box-Behnken designs: 13 exp.
Doehlert designs: 13 exp.
Uniform designs: 6 exp.
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DoelVerschillende response surface designs in optimalisatie vergelijken, welke meest geschikt?
3 factoren verschillend aantal experimenten !
Three-level full factorial designs: 33=27 exp.
Central composite designs: 23+6+min1= min 15 exp.
Box-Behnken designs: 13 exp.
Doehlert designs: 13 exp.
Uniform designs: 6 exp.
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DoelVerschillende response surface designs in optimalisatie vergelijkenGebruikte toepassing?Optimalisatie scheiding HPLC/CEOptimalisatie derivatisatiereactieInvloed van aantal exp ? Welk optimum wordt voorspeld uit elk design?Welke voorspelde optima leveren praktisch ook goede resultaten op?Vergelijken voorspelde waarde met experimentele waarde bij gevonden optima
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VINGERAFDRUK ANALYSEvan kruiden d.m.v. HPLC/DADGoedele Alaerts Christophe Tistaert
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Vingerafdruk analyse van kruidenBelang onderzoek kwaliteit van kruiden:
Vermageringskuur op basis van chinese kruidenNefropathie: nierdialyse niertransplantatieVerwisselingAristolochia fangchi i.p.v.Stephania tetrandra 1990-1992
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Vingerafdruk analyse van kruidenNood aan identificatie kruidenkwaliteitscontrole kruiden
Kruid = complex mengsel !
Bepaling enkele componentenOnvoldoende voor intrinsieke kwaliteit?
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Vingerafdruk analyse van kruidenOplossing: fingerprintsKarakteristieke vingerafdrukInfra Rood (IR)Massa spectrofotometrie (MS)Dunne laag chromatografie (DLC)Hoge druk vloeistofchromatografie (HPLC)Capillaire Electroforese (CE)
Chromatografische fingerprint Geaccepteerd door WHO !
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Vingerafdruk analyse van kruidenExperimenteel deel: Fingerprint ontwikkeling en optimalisatie d.m.v. HPLC/DADDataverwerking: Hoe kruiden onderscheiden op basis van hun fingerprints ? (Correlatiecofficienten of PCA) (Goedele)Modelleren van antioxiderende / cytotoxische activiteit i.f.v. de fingerprints en identificatie van de componenten die voor de activiteit verantwoordelijk zijn. (Christophe)
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Vingerafdruk analyse van kruiden
Sheet1
Figure 2 screeningNOG OP 1 FIGUUR ZETTENzonder integeratie op dezelf de schaal onder elkaar
serie 20 5-60% ACN
serie21 5-95% MeOH
serie 27 5-50 % iPrOH
serie 26 5-50% THF
Sheet2
serie 20serie 21serie 27serie26
Figure 2 Liqourice screening5-60% ACN5-95 % MeOH5-50% iPrOH5-50% THF
Retention time (min)
00.003-0.004-0.0040.003
0.003330.003-0.004-0.0040.003
0.006670.003-0.004-0.0040.003
0.010.003-0.004-0.0040.003
0.013330.003-0.004-0.0040.003
0.016670.003-0.004-0.0040.003
0.020.003-0.004-0.0040.003
0.023330.003-0.004-0.0040.003
0.026670.003-0.004-0.0040.003
0.030.003-0.004-0.0040.003
0.033330.003-0.004-0.0040.003
0.036670.003-0.003-0.0040.003
0.040.003-0.003-0.0040.003
0.043330.003-0.003-0.0040.002
0.046670.003-0.003-0.0040.002
0.050.003-0.003-0.0040.002
0.053330.003-0.003-0.0040.002
0.056670.003-0.003-0.0040.002
0.060.003-0.003-0.0040.002
0.063330.003-0.003-0.0040.002
0.066670.003-0.003-0.0040.002
0.070.003-0.003-0.0040.002
0.073330.003-0.003-0.0040.002
0.076670.003-0.003-0.0030.002
0.080.003-0.003-0.0030.002
0.083330.003-0.003-0.0030.002
0.086670.003-0.003-0.0030.002
0.090.003-0.003-0.0030.002
0.093330.003-0.003-0.0030.002
0.096670.003-0.003-0.0030.002
0.10.003-0.003-0.0030.002
0.103330.003-0.003-0.0020.002
0.106670.003-0.003-0.0020.002
0.110.003-0.003-0.0020.002
0.113330.003-0.003-0.0020.002
0.116670.003-0.00300.002
0.120.003-0.00300.002
0.123330.003-0.00300.002
0.126670.003-0.00300.002
0.130.003-0.00300.002
0.133330.003-0.00300.002
0.136670.003-0.00300.002
0.140.003-0.00300.002
0.143330.003-0.00300.002
0.146670.003-0.00300.002
0.150.003-0.00300.002
0.153330.003-0.00300.002
0.156670.003-0.00300.004
0.160.003-0.00300.006
0.163330.003-0.00300.007
0.166670.003-0.00300.008
0.170.003-0.00300.01
0.173330.003-0.00300.011
0.176670.003-0.00300.012
0.180.003-0.00300.014
0.183330.003-0.00300.015
0.186670.003-0.00300.015
0.190.003-0.00300.015
0.193330.003-0.00300.015
0.196670.003-0.00300.016
0.20.003-0.00300.016
0.203330.003-0.00300.016
0.206670.003-0.00300.016
0.210.003-0.00300.016
0.213330.003-0.00300.016
0.216670.003-0.00300.016
0.220.003-0.00300.016
0.223330.003-0.00300.016
0.226670.003-0.00300.014
0.230.003-0.00300.011
0.233330.003-0.00300.009
0.236670.003-0.00300.007
0.240.003-0.00300.006
0.243330.003-0.00300.006
0.246670.003-0.00300.006
0.250.003-0.00300.006
0.253330.003-0.00300.004
0.256670.003-0.00300
0.260.003-0.0030-0.004
0.263330.003-0.0030-0.006
0.266670.003-0.0030-0.008
0.270.003-0.0030-0.008
0.273330.003-0.0030-0.008
0.276670.003-0.0030-0.008
0.280.003-0.0030-0.008
0.283330.003-0.0030-0.008
0.286670.003-0.0030-0.008
0.290.003-0.0030-0.008
0.293330.003-0.0030-0.008
0.296670.003-0.0030-0.008
0.30.003-0.0030-0.008
0.303330.003-0.0030-0.008
0.306670.003-0.0030-0.008
0.310.003-0.0030-0.008
0.313330.003-0.0030-0.008
0.316670.003-0.0030-0.008
0.320.003-0.0030-0.008
0.323330.003-0.0030-0.008
0.326670.003-0.0030-0.008
0.330.003-0.0030-0.007
0.333330.003-0.0030-0.007
0.336670.003-0.0030-0.007
0.340.003-0.0030-0.007
0.343330.003-0.0030-0.007
0.346670.003-0.0030-0.007
0.350.003-0.0030-0.006
0.353330.003-0.0030-0.005
0.356670.003-0.0030-0.005
0.360.003-0.0030-0.005
0.363330.003-0.0030-0.004
0.366670.003-0.0030-0.004
0.370.003-0.0030-0.004
0.373330.003-0.0030-0.004
0.376670.003-0.0030-0.004
0.380.003-0.0030-0.004
0.383330.003-0.0030-0.004
0.386670.003-0.0030-0.004
0.390.003-0.0030-0.003
0.393330.003-0.0030-0.003
0.396670.003-0.0030-0.003
0.40.003-0.0030-0.003
0.403330.003-0.0030-0.003
0.406670.003-0.0030-0.002
0.410.003-0.0030-0.002
0.413330.003-0.0030-0.002
0.416670.003-0.00300
0.420.003-0.00300
0.423330.003-0.00300
0.426670.003-0.00300
0.430.003-0.00300
0.433330.003-0.00300
0.436670.003-0.00300
0.440.003-0.00300
0.443330.003-0.00300
0.446670.003-0.00300
0.450.003-0.00300
0.453330.003-0.00300
0.456670.003-0.00300
0.460.003-0.00300
0.463330.003-0.00300
0.466670.003-0.00300
0.470.003-0.00300
0.473330.003-0.00300
0.476670.003-0.00300
0.480.003-0.00300
0.483330.003-0.00300
0.486670.003-0.00300
0.490.003-0.00200
0.493330.003-0.00200
0.496670.003-0.00200
0.50.003-0.00200
0.503330.003-0.00200
0.506670.003-0.00200
0.510.003-0.00200
0.513330.003-0.00200
0.516670.003-0.00200
0.520.003-0.00200
0.523330.003-0.00200
0.526670.003-0.00200
0.530.003-0.00200
0.533330.003-0.00200
0.536670.003-0.00200
0.540.003-0.00200
0.543330.003-0.00200
0.546670.003-0.00200
0.550.003-0.00200
0.553330.003-0.00200
0.556670.003-0.00200
0.560.003-0.00200
0.563330.003-0.00200
0.566670.003-0.00200
0.570.003-0.00200
0.573330.003-0.00200
0.576670.003-0.00200.001
0.580.003-0.00200.002
0.583330.003-0.0020.0010.002
0.586670.003-0.0020.0010.002
0.590.003-0.0020.0020.003
0.593330.003-0.0020.0020.004
0.596670.003-0.0020.0020.005
0.60.003-0.0020.0020.005
0.603330.003-0.0020.0020.005
0.606670.003-0.0020.0020.005
0.610.003-0.0020.0020.005
0.613330.003-0.0020.0020.005
0.616670.003-0.0020.0020.005
0.620.003-0.0020.0020.005
0.623330.003-0.0020.0020.005
0.626670.003-0.0020.0020.005
0.630.003-0.0020.0020.005
0.633330.003-0.0020.0020.005
0.636670.003-0.0020.0020.005
0.640.003-0.0020.0020.005
0.643330.003-0.0020.0020.005
0.646670.003-0.0020.0020.005
0.650.003-0.0020.0020.005
0.653330.002-0.0020.0020.004
0.656670.002-0.0020.0020.003
0.660.001-0.0020.0020.003
0.663330.001-0.0020.0020.003
0.666670.001-0.0020.0020.003
0.670.001-0.0020.0020.002
0.673330.001-0.0020.0020.002
0.676670.001-0.0020.0020.002
0.680.001-0.0020.0020.002
0.683330.001-0.0020.0020.002
0.686670.001-0.0020.0020.002
0.690.001-0.0020.0020.002
0.693330.001-0.0020.0020.002
0.696670.001-0.0020.0020.002
0.70.001-0.0020.0020.002
0.703330.001-0.0020.0020.002
0.706670.001-0.0020.0020.002
0.710.001-0.0020.0020.002
0.713330.001-0.0020.0020.002
0.716670.001-0.0020.0020.002
0.720.001-0.0020.0020.002
0.723330.002-0.0020.0020.002
0.726670.002-0.0020.0020.002
0.730.003-0.0020.0020.002
0.733330.004-0.0020.0020.002
0.736670.005-0.0020.0020.002
0.740.005-0.0020.0020.002
0.743330.005-0.0020.0020.002
0.746670.005-0.0020.0020.002
0.750.005-0.0020.0020.002
0.753330.005-0.0020.0020.002
0.756670.005-0.0020.0020.002
0.760.005-0.0020.0020.002
0.763330.005-0.0020.0020.002
0.766670.005-0.0020.0020.002
0.770.005-0.0020.0020.002
0.773330.005-0.0020.0020.002
0.776670.005-0.0020.0020.002
0.780.005-0.0020.0020.002
0.783330.005-0.0020.0020.002
0.786670.005-0.0020.0020.002
0.790.005-0.0020.0020.002
0.793330.005-0.0020.0020.002
0.796670.005-0.0020.0020.002
0.80.005-0.0020.0020.002
0.803330.005-0.0020.0020.002
0.806670.005-0.0020.0020.002
0.810.005-0.0020.0020.002
0.813330.005-0.0020.0020.002
0.816670.005-0.0020.0020.002
0.820.005-0.0020.0020.002
0.823330.005-0.0020.0020.002
0.826670.005-0.0020.0020.002
0.830.005-0.0030.0020.002
0.833330.005-0.0030.0020.002
0.836670.005-0.0030.0020.002
0.840.005-0.0030.0020.002
0.843330.005-0.0030.0020.002
0.846670.005-0.0030.0020.002
0.850.005-0.0030.0020.002
0.853330.005-0.0030.0020.002
0.856670.005-0.0030.0020.002
0.860.005-0.0030.0020.002
0.863330.005-0.0030.0020.002
0.866670.005-0.0030.0020.002
0.870.005-0.0030.0020.002
0.873330.005-0.0030.0020.002
0.876670.005-0.0030.0020.002
0.880.005-0.0030.0020.002
0.883330.005-0.0040.0020.002
0.886670.005-0.0040.0020.002
0.890.005-0.0050.0020.002
0.893330.005-0.0060.0020.002
0.896670.005-0.0060.0020.003
0.90.005-0.0060.0020.004
0.903330.005-0.0060.0020.004
0.906670.005-0.0060.0020.004
0.910.005-0.0060.0020.004
0.913330.005-0.0060.0020.004
0.916670.005-0.0060.0020.004
0.920.005-0.0060.0020.004
0.923330.005-0.0060.0020.004
0.926670.005-0.0060.0020.004
0.930.005-0.0060.0020.004
0.933330.005-0.0060.0020.004
0.936670.005-0.0060.0020.004
0.940.005-0.0060.0020.004
0.943330.005-0.0060.0020.004
0.946670.005-0.0060.0020.004
0.950.005-0.0060.0020.004
0.953330.005-0.0060.0020.004
0.956670.005-0.0060.0020.004
0.960.005-0.0060.0020.004
0.963330.005-0.0060.0020.004
0.966670.005-0.0060.0020.004
0.970.005-0.0060.0020.004
0.973330.005-0.0060.0020.004
0.976670.005-0.0060.0020.004
0.980.005-0.0060.0020.004
0.983330.005-0.0060.0020.004
0.986670.005-0.0060.0020.004
0.990.005-0.0060.0020.004
0.993330.005-0.0060.0020.004
0.996670.005-0.0060.0020.004
10.005-0.0060.0020.004
1.003330.005-0.0060.0020.004
1.006670.005-0.0060.0020.004
1.010.005-0.0060.0020.004
1.013330.005-0.0060.0020.004
1.016670.005-0.0060.0020.004
1.020.005-0.0060.0020.004
1.023330.005-0.0060.0020.004
1.026670.005-0.0060.0020.004
1.030.005-0.0060.0020.004
1.033330.005-0.0060.0020.004
1.036670.005-0.0060.0020.004
1.040.005-0.0060.0020.004
1.043330.005-0.0060.0020.004
1.046670.005-0.0060.0020.004
1.050.005-0.0060.0020.004
1.053330.005-0.0060.0020.004
1.056670.005-0.0060.0020.004
1.060.005-0.0060.0020.004
1.063330.005-0.0060.0020.004
1.066670.005-0.0060.0020.004
1.070.005-0.0060.0020.004
1.073330.005-0.0060.0020.004
1.076670.005-0.0060.0020.004
1.080.005-0.0060.0020.004
1.083330.005-0.0060.0020.004
1.086670.005-0.0060.0020.004
1.090.005-0.0060.0020.004
1.093330.005-0.0060.0020.004
1.096670.005-0.0060.0020.004
1.10.005-0.0060.0020.004
1.103330.005-0.0060.0020.004
1.106670.005-0.0060.0020.004
1.110.005-0.0060.0020.004
1.113330.005-0.0060.0020.004
1.116670.005-0.0060.0020.004
1.120.005-0.0060.0020.004
1.123330.005-0.0060.0020.004
1.126670.005-0.0060.0020.004
1.130.005-0.0060.0020.004
1.133330.005-0.0060.0020.004
1.136670.005-0.0060.0020.004
1.140.005-0.0060.0020.004
1.143330.005-0.0060.0020.004
1.146670.005-0.0060.0020.004
1.150.005-0.0060.0020.004
1.153330.005-0.0060.0020.004
1.156670.005-0.0060.0020.004
1.160.005-0.0060.0020.004
1.163330.005-0.0060.0020.004
1.166670.005-0.0060.0020.004
1.170.005-0.0060.0020.004
1.173330.005-0.0060.0020.004
1.176670.005-0.0060.0020.004
1.180.005-0.0060.0020.004
1.183330.005-0.0060.0020.004
1.186670.005-0.0060.0020.004
1.190.005-0.0060.0020.004
1.193330.005-0.0060.0020.004
1.196670.005-0.0060.0020.004
1.20.005-0.0060.0020.005
1.203330.005-0.0060.0020.005
1.206670.005-0.0060.0020.006
1.210.005-0.0060.0020.006
1.213330.005-0.0060.0020.006
1.216670.005-0.0060.0020.006
1.220.005-0.0060.0020.006
1.223330.005-0.0060.0020.006
1.226670.005-0.0060.0020.006
1.230.005-0.0060.0020.006
1.233330.005-0.0060.0020.006
1.236670.005-0.0060.0020.006
1.240.005-0.0060.0020.006
1.243330.005-0.0060.0020.006
1.246670.005-0.0060.0020.006
1.250.005-0.0060.0020.006
1.253330.005-0.0060.0020.006
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