Computer aided formulation development

Computer in pharmacy, Ethics of computing, concept of optimization and parameters

1. COMPUTER -AIDED
FORMULATION DEVELOPMENT
PREPARED BY –Ms. SHRUTI TYAGI
M. Pharm: Pharmaceutics
Lecturer in Pharmacy (B.S. Anangpuria Institute of Pharmacy)

2. POINTS TO BE CONSIDERED -
•Conceptofoptimization.
•Parametersofoptimization,Factorialdesign.
•Useofcomputersinoptimization.
•OptimizationofvariousDrugproductsandpharmaceutical
processes.
•LegalProtectionofInnovativeUsesofComputersinR&D.
•EthicsofComputinginPharmaceuticalResearch.
•ComputersinMarketanalysis.

3. Concept of optimization
Optimizationhasbeendefinedastheimplementationofschematic
approachestoachievethebestcombinationofproductand/orprocess
characteristicsunderagivensetofconditions.
Designanddevelopmentofdrugformulationorpharmaceuticalprocess
usuallyinvolvesseveralvariables.Theinputvariables,whichare
directlyundercontroloftheproductdevelopmentscientist,areknown
asINDEPENDENT VARIABLESe.g.,compressionalforce,excipient
amount,mixingtimeetc.(suchvariablesareeitherQUALITATIVEor
QUANTITATIVE).
Theinputvariables,whicharedirectlydependentupontheindependent
variables,areknownasDEPENDENT VARIABLESe.g.,hardness,
disintegrationtime,dissolutiontimeetc.

4. Parameters of optimization
PROBLEM TYPE
Constrained
Unconstrained
VARIABLES
Independent
Dependent

5. EXAMPLESOFPARAMETERS OFOPTIMIZATION
1.ProblemTypes
Constrained:Makinghardesttabletwhichdisintegrateswithin20min
Unconstrained:Makinghardesttablet
2.Variables
Independent:Mixingtimeforagivenprocessstep,Granulatingtime
Dependent:Particlesizeofvesicles,hardnessofthetablet

6. TYPES OF EXPERIMENTAL DESIGNS
•Completelyrandomizeddesigns.
•Randomizedblockdesigns.
•Factorial designs -1. Full factorial designs
2. Fractional factorial designs
•Responsesurfacedesigns.
•Centralcompositedesigns.
•Box-Behnkendesigns.
•Threelevelfullfactorialdesigns.

7. Thesedesignscomparethe
valuesofaresponsevariable
basedondifferentlevelsof
thatprimaryfactor.
Exampleifthereare3levels
ofprimaryfactorwitheach
leveltoberun2timesthen
thereare6factorialpossible
runsequence.
1.Completelyrandomizeddesigns-
ADIAGRAMATIC REPRESENTATION OFCOMPLETELY RANDOMIZED DESIGN.

8. 2.Randomizedblockdesigns-
Forthistypeofdesignthereisonefactororvariablethatisofprimary
interest(tocontrolthenon-significantfactors,animportanttechnique
calledblockingisusedtoreduceoreliminatethecontributionofthese
factorstoexperimentalerrors).
ADIAGRAMATIC REPRESENTATION OFRANDOMIZED DESIGN.

9. 3.FactorialDesigns-
Thesearethedesignsofchoiceforsimultaneousdetermination
oftheeffectsofseveralfactorsandthereinteractions.
Symbolstodonatelevelsare-
(1)-whenboththevariablesareinlowconcentrations.
(a)-onelowvariableandsecondhighvariable.
(b)-onehighvariableandsecondlowvariable.
(ab)-whenboththevariablesareinhighconcentrations.
Forinstance-factorialdesignsareoptimaltodeterminethe
effectofpressureandlubricantonthehardnessoftablet.
Otherexampleis,effectofdisintegrantandlubricant
concentrationontabletdissolution.

10. A)FullFactorialdesigns-usedforsmallsetoffactors.
B)Fractionaldesigns-usedtoexaminemultiplefactorsefficientlywithfewer
runsthancorrespondingfullfactorialdesigns.
Typesoffractionalfactorialdesigns:-
•Homogeneousfractionalfactorialdesigns-usedwhenlargenumberof
factorsmustbescreened.
•Mixedlevelfractionalfactorialdesigns-usedwhenvarietyoffactorsneedto
beevaluatedformaineffectsandhigherlevelinteractionscanbeassumedto
benegligible,objectiveistogenerateadesignforonevariable,A,at2levels
andanother,X,at3levels,mixedandevaluated.
•Box-Hunterdesign
•Plackett-Burmandesign
•Tiguchi
•Latin-Square

12. 4.Response surface designs-
This model has quadratic designs-
γ = β
0+ β
1X
1+ β
2X
2+....... β
11 (X
1)
2
+ β
22(X
2 )
2
Designs for fitting these type of models are known as
response surface designs. If defects and yields are the
outputs and the goal is to minimise defects and
maximize yields.
Most common designs generally used in this response
surface designs are:
•Central composite design
•Box-Behnken design

13. A)Central composite designs-
Thecentralcompositedesigncontainsembeddedfactorialorfractional
factorialdesignswithcenterpointsthatisaugmentedwithgroupofstar
points,thesealwayscontaintwiceasmanystarpointsasthereare
factorsinthedesigns.
Thestarpointsrepresentsnewextremevalue(lowandhigh)foreach
factorinthedesign.Theseareofthreetypes-
•Circumscribeddesign-cubepointsareatthecornersofunitcube,
starpointsarealongtheaxisatoroutsidethecube,andcenterpointat
theorigin.
•Inscribeddesign-starpointstakethevalueof+1and-1andcube
pointslieintheinteriorofthecube.
•Faceddesign-starpointsareonthefacesofcube.

14. CENTRAL COMPOSITE DESIGN

15. B) Box-Behnken design-
Usesjustthreelevelsofeach
factor,inthisdesignthetreatment
combinationsareatthemidpoints
oftheedgesoftheprocessspace
andatthecenter.Thesedesigns
arerotatableornearrotatableand
requirethreelevelsofeach
factor.Thesedesignsareforthree
factorswithcirclepoints
appearingattheoriginand
possiblyrepeatedforseveralruns.
Itisanalternativetocentral
compositedesign.

16. 5.Three level full factorial design-
Itiswrittenas3kfactorialdesign.Itmeansthatkfactorsareconsidered
eachatthreelevels.Theseareusuallyreferredtoaslow,intermediate
andhighvalues,whichareusuallyexpressedas0,1and2.Thethird
levelforacontinuousfactorfacilitatesinvestigationofaquadratic
relationshipbetweentheresponseandeachofthefactors.

17. DESIGN MERIT LIMITATION
FACTORIAL Efficient in estimating main effects and
interactions.
Reflection of curvature is not
possible in a 2 level design, large
number of experiments are required.
FRACTIONAL
FACTORIAL
Suitable for large number of factor or factor
levels.
Effects can not be uniquely
estimated, as are confounded with
interaction terms, difficult to
construct.
PLACKET-BURMAN Suitable for very large number of factors,where
even full factorial designs require a large number
of experiments.
Fixed designs in which runs are
predetermined and are limited to ≤16
experiments.
CENTRAL
COMPOSITE
Allows the work to proceed in stages. Difficult to practice with fractional
values of α

18. Use of computers in optimization
Nowadays,computeruseisconsideredalmostindispensableinthedesignand
optimizationmethods,asagreatdealofintricatestatisticalandmathematical
calculationsareinvolved.Thecomputersoftwarehavebeenusedalmostateverystep
duringtheentireoptimizationcyclerangingfromselectionofdesign,screeningof
factors,useofresponsesurfacedesigns,generationofthedesignmatrix,plottingof3D
responsesurfacesand2Dcontourplots,applicationofoptimumsearchmethods,
interpretationoftheresults,andfinallythevalidationofthemethodology.Some
importantcomputersoftwaresusedinoptimizationareasfollows:-
•Designexpert
•MINITAB
•JMP
•MATREX
•Cornerstone
TM
•STATISTICA
•NEMROD@

19. Optimization of various Drug products and
pharmaceutical processes
LiquidFormulations:-Thereareseveralreportsonoptimizationsviz.
emulsions,solutions,suspensions,lotions,etc.Amongsttheophthalmic
andparentralformulations,solubility,chemicalstabilityandviscosity
havebeenoptimizedbyvaryingtheformulationcomposition.
Emulsions,microemulsions,solutions,lotionsorsuspensionshavebeen
optimizedforresponsesasturbidity,cloudpoint,physicalstability,
preservativeefficacyetc.,primarilybyalteringthelevelsofthe
ingredients.TheFactorialdesignandCentralcompositedesignhave
beenutilisedastheexperimentaldesigns,withthenumberof
independentvariablesrangingbetween2to8andresponsesbetween1
and5.

20. S.NO. TYPE DRUG DESIGN INPUT
VARIABLES
RESPONSE
VARIABLES
1. Syrup AcetaminophenRSM 4 2
2. Emulsion Oxybenzone SMD 3 3
3. Lotion Erythromycin CCD 3 1
4. Suspension Rifampicin FD 4 5
5. Oral solutionLamivudine CCD 5 2
6. MicroemulsionRetinol SMD 4 1
7. Ophthalmic
formulation
Enalkrien FD 3 1
8. Parenteral
nutrition
Nutrient mixturesPBD 5 1
9. Solution Diazepam SMD 3 1
Optimization reports on liquid dosage forms
RSM-Response surface methodology, SMD-Simplex mixture design, CCD-Central composite design, FD-Factorial design,
PBD-Placket-Burman design.

21. Thevariousnovelandinnovativeusesofcomputersplaysavitalrolein
drugformulationanddevelopment,theseusesofcomputersinthe
researchanddevelopmentsectorcanbeprotectedlegallythrough
intellectualpropertyrights.Intellectualpropertyrightsseektoprotect
knowledgederivedfromresearchanddevelopmentespeciallybyfirms
involvedincollaborationswithotherstoensurethattheknowledgeisnot
expropriatedbytheirpotentialpartners.Thelackofintellectualproperty
rightsreducesthebargainingpowerofcollaborationpartnersand
increasecostsofinformationforsuchpartners.Theexistenceof
protectivemechanismsoverintellectualassetsisessentialtoenhancethe
competitivenessoforganisationsespeciallythoseworkingonR&D
relatedissuesaswellastoattractpotentialinvestors.
Legal Protection of Innovative Uses of Computers in
Research and Development

22. Ethics of Computing in Pharmaceutical Research
Computerethicsisapartofpracticalphilosophyconcernedwithhow
computingprofessionalsshouldmakedecisionsregardingprofessionaland
socialconduct.MargaretAnnePierce,aprofessorintheDepartmentof
MathematicsandComputersatGeorgiaSouthernUniversityhascategorized
theethicaldecisionsrelatedtocomputertechnologyandusageintothree
primaryinfluences:
•Theindividual'sownpersonalcode.
•Anyinformalcodeofethicalconductthatexistsintheworkplace.
•Exposuretoformalcodesofethics.
Privacyisoneofthemajorissuesthathasemergedsincetheinternethas
becomepartofmanyaspectsofdailylife.Internetusershandoverpersonal
informationinordertosignuporregisterforserviceswithoutrealizingthat
theyarepotentiallysettingthemselvesupforinvasionsofprivacy.

23. Identifyingissues
Identifyingethicalissuesastheyarise,aswellasdefininghowtodealwith
them,hastraditionallybeenproblematic.Insolvingproblemsrelatingto
ethicalissues,MichaelDavisproposedauniqueproblem-solvingmethod.In
Davis'smodel,theethicalproblemisstated,factsarechecked,andalistof
optionsisgeneratedbyconsideringrelevantfactorsrelatingtotheproblem.
Theactualactiontakenisinfluencedbyspecificethicalstandards.
Ethicalstandards
Variousnationalandinternationalprofessionalsocietiesandorganizations
haveproducedcodeofethicsdocumentstogivebasicbehavioralguidelines
tocomputingprofessionalsandusers.Theyinclude:
1.AssociationforComputingMachinery
ACMCodeofEthicsandProfessionalConduct

24. 2. Australian Computer Society
•ACS Code of Ethics
•ACS Code of Professional Conduct
3. British Computer Society
•BCS Code of Conduct
•Code of Good Practice (retired May 2011)
•Computer Ethics Institute
•Ten Commandments of Computer Ethics marri
4. IEEE
•IEEE Code of Ethics
•IEEE Code of Conduct
5. League of Professional System Administrators
•The System Administrators' Code of Ethics

25. Computers in Market analysis
Amarketanalysisstudiestheattractivenessandthedynamicsofa
specialmarketwithinaspecialindustry.Itispartoftheindustry
analysisandthusinturnoftheglobalenvironmentalanalysis.
Throughalloftheseanalyses,thestrengths,weaknesses,
opportunitiesandthreats(SWOT)ofacompanycanbeidentified.
Finally,withthehelpofaSWOTanalysis,adequatebusiness
strategiesofacompanywillbedefined.Themarketanalysisisalso
knownasadocumentedinvestigationofamarketthatisusedto
informafirm'splanningactivities,particularlyarounddecisionsof
inventory,purchase,workforceexpansion/contraction,facility
expansion,purchasesofcapitalequipment,promotionalactivities,
andmanyotheraspectsofacompany.

26. References
1. Bhupinder Singh, R.K.Gupta and Naveen Ahuja, “Computer
assisted optimization of pharmaceutical formulations and
processes”, page no. 273-318.
2. Nazura Abdul Manap, Rohimi Bin Shapiee, Pardis
Moslemzedah Tehrani and Ahmad Azam bin Mohd. Shariff,
“Protecting R&D Inventions through Intellectual Property
Rights”: Journal of Intellectual Property Rights:Vol 21, March
2016, pp 110-116.
3. Pharmaceutical Optimization by G.T.Kulkarni.

27. THANK YOU