Computer-aided design and optimization for pharmaceutical ...

More documents

Recommendations

Info

A novel method to setup the design spaceSuper spherical solution vectors which satisfyspecifications of response variablesLeave-oneone-factor-out out method(Simulated gene knockout method)Optimal solutions estimated from bootstrap samplesWild typeKnockoutx3rSolution vectorssatisfiedspecificationsof responsevariablesY * optim, originalY * optim, LOFOBootstrap samplingDifference of mean and SD betweenY * optim, original and Y * optim, LOFO couldrepresent the statistical importance ofrelevant factor.CentroidX=(X 1 , X 2 ,…, X n )Y=(Y 1 , Y 2 ,…, Y m )X=(X 1 , X 2 ,…X i ,…, X n )Y=(Y 1 , Y 2 ,…, Y m )X ix2x1Original datasetLOFO datasetLeave-one-factor-out fromthe original dataset.Case studyPowder properties of theophylline powder formulations·Formulation factorsX 1: mixing ratio of lactoseX 2: mixing ratio of corn starchX 3: mixing ratio of microcrystalline cellulose·Response variablesY 1: angle of reposeY 3: degree of cohesionExperimental designX 1Y 2: compressibility ratioY 4: dispersion ratio·Process variablesZ 1: amount of magnesium stearateZ 2: mixing timeCase studyFormula optimization of ketoprofen hydrogel using RSM-SFormulation factorsX 1: 1-O-ethyl1ethyl-3-n-butylcyclohexanol(OEBC) (%)Response variablesY 1: Penetration rate (Rp) (µg/h)(Y 2: Total irritation score (TIS)X 2: Diisopropyl adipate (DIA) (%)X 3: Isopropanol (IPA) (%)Simultaneous optimal solutionFormulation factorsOEBC(%)DIA(%)IPA(%)1.264.8731.7Z 1Z 2Response variablesRp(µg/h)TISX 2 X 3Simplex lattice designCentral composite sphericalsecond- order experimental design341.64.17
Design space for ketoprofen hydrogelsSpecification of response variables: Rp ≥ 300µg/h and TIS ≤ 5.0Design space offormulation factorsOEBC (%) : 1.21 – 1.32DIA (%) : 4.76 – 5.00IPA (%) : 30.9 – 32.4Background‣ ICH ICH Q8 Q8 draft consensus guideline‣ PAT PAT guidance for for industryGeneral concept of RSM-S‣ Thin-plate spline interpolation‣ Bootstrap re-sampling‣ Kohonen’s s self-organization mapsCase examples‣ Formulation optimization of of Theophylline tablets‣ Formulation optimization of of PEGylated emulsionscontaining paclitaxelResponse surfaces generated by thin-plate spline as afunction of smoothing parameter (λ)(actual surfacewith λ too largeFactor levels predicted as an optimal conditionFactorQPE a) ANN b) MVS c)x 1 : amount of soybean oil (mg/mL) 5.60 5.52 5.75x 2 : amount of PEG-DSPE (mg/mL) 2.26 2.18 2.32x 3 : amount of polysorbate 80 (mg/mL) 42.5 35.9 44.6a) Predicted by the quadratic polynomial equation.b) Predicted by the artificial neural network.c) Predicted by the multivariate spline interpolation.with λ too smallwith λ estimated by GCVResponse levels predicted as an optimal conditionResponseQPEANNMVSy 1 : entrapment efficiency (%)a)95.9 101 97.3y 2 : particle size (nm) 265 262 269a) The amount of paclitaxel initially loaded was fixed to be 0.6 mg/mL. mG. Wahba, Spline Models for Observational Data,Siam, Philadelphia, Pennsylvania, pp48-50, 1990.
Page 1 and 2: Computer-aided design andoptimizati
Page 3 and 4: Computer-aided design and optimizat
Page 5 and 6: Output layerInput vectorX1, X2, …
Page 7 and 8: 95% Confidence interval for optimal
Page 9: ConclusionsA response surface metho
Page 13: AlgorithmBasic concept of biharmoni

Computer-aided design and optimization for pharmaceutical ...

Create successful ePaper yourself

Delete template?

Save as template?