• No se han encontrado resultados

Formulation factors affecting the binding properties of chinese yam (dioscorea oppositifolia) and corn starches

N/A
N/A
Protected

Academic year: 2023

Share "Formulation factors affecting the binding properties of chinese yam (dioscorea oppositifolia) and corn starches"

Copied!
7
0
0

Texto completo

(1)

G /vys/ts/ScrsiG r/e

Formulation factors affecting the binding properties of Chi­

nese yam ( Dioscorea oppositifolia) and corn starches

Adenike Okunlola, Oluwatoyin A. Odeku

Department o f Pharmaceutics and Industrial Pharmacy, University o f Ibadan, Ibadan , Nigeria

Received June 25 , 2009; Accepted August 2 6 , 2009

Abstract

Objective;

The quantitative effects o f formulation and processing variables affecting the binding properties of Chinese yam starch ( Dioscorea oppositifolia) in chloroquine phosphate tablet formulations have been investiga­

ted in comparison with com starch using a 23 factorial experimental design.

Methods

: Chinese yam starch, re­

presenting the "lo w " level, and co m starch, representing the "h ig h " level were used as binders at concentra­

tions of 2. 5 % w /w and 10 % w /w in chloroquine phosphate tablet formulations. The mechanical properties of the tablets, measured by the tensile strength ( T ) and brittle fracture index ( B F I) as well as the release prop­

erties measured by the disintegration time ( D T ) and dissolution time ( t g0- time for 80 % drug release) , were used as assessment parameters.

Results;

The ranking o f the individual coefficient values for the formulations on T was D > N » C , on BFI was N > D » C , on DT was D > N > C and on t80 was C > N > D while the ranking of the interaction coefficient on T was N-D > C-D » N -C , on BFI was N-D > N-C = C -D , on DT and t80 was N-C > N-D > C-D. Changing the binding agent from Chinese to com starch, led to a decrease in T , DT and tg0 but increase in BFI o f the tablets. There were significant ( P < 0 . 0 0 1 ) interactions between the nature o f binder, N and the other two variables, C and D.

Conclusion;

The result showed that Chinese yam possessed stronger binding capacity than com starch and could be useful as an alternative binder when tablets with high mechanical strength with minimal problems o f lamination, and slow release are required.

Keywords;

Starch

;

B inder; Chinese yam ;Tensile strength; Brittle fracture index; Chloroquine phosphate

INTRODUCTION

Starches are o f commercial importance in the food and phamiaceutical industries because o f their inert­

ness, abundance and cheapness. Commercial star­

ches obtained from cereals ( co rn , waxy c o m , high amylose c o m , wheat and various rice s) , tubers and roots ( particularly potato and cassava) are used as diluents, binders and disintegrants in drug formula-

Correspondence lo ; Dr. Oluwatoyin A. Odeku, Department of Phar­

maceutics & Industrial Pharmacy, Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.

Tel; 2348057320466; 23428106403 E-mail; pejuodeku@ yahoo, com

tiont l] . With the versatility o f starches in various solid dosage forms, there is the need to continue to develop new starch excipients with suitable proper­

ties to meet the special needs o f drug formulators.

Tropical yam tubers (Fam ily D ioscoreaceae) are potential source o f industrial starch because o f their high starch content ( about 50 - 80 % w /w ) ^ . One o f the species cultivated in many parts o f Africa and Southeast Asia is Dioscorea oppositifolia ( Chinese yam) , which has been used in Chinese medicine as an invigorant 3 . D. oppositifolia L. , (a ls o known as D. opposita Thunb) , is a perennial twining vine which has a d e e p , persistent root-like tuber that can be 1 m long and weigh up to several kilograms.

Aboveground, it has round slender stems that twine

© 2 0 0 9 . Asian Pacific Journal of Tropical Medicine. 1

UNIVERSITY OF IBADAN LIBRARY

(2)

dextrorselyupwardsandleavesthatareusuallyar rangedoppositely.Thespeciesepithet"oppositifo lia"referstothisoppositearrangementofitsleaves. Recentstudiesonthephysicochemical,materialand tabletpropertiesofChineseyam starchhaveshown thatthevariedconsiderablyfrom officialcornstarch andstarchesfrom otherDioscoreaspecies.Chi neseyamstarchhasanamylose,protein,ash,lipid andphosphoruscontentof21.61,0.75,0.21, 020and0.025% respectively.Whenusedasadi rectlycompressibleexcipient,Chineseyam starch wasobservedtobehighlycompressible,formingtab letsofacceptablecrushingforce.Thecompact ibilityofthestarchappearedtoberelatedtothe granulesize,irregularshapeandhighspecificsur faceareawhichfacilitatemoreinterparticulatecon tactandthushigherbondformation.Furtherstud ieshaveshownthatthestarchcouldbeusefulatcer tain concentrations as disintegrants particularly wherehighmechanicalstrengthandagoodbalance betweenbindingandreleasepropertiesofthetablets arerequired.However,thequantitativeeffectsof importantformulationandprocessingvariablesonthe bindingpropertiesofChineseyam starchappearto be largely uninvestigated. Thus,in the present work,thequantitativeeffectsofformulationandpro cessingvariablesaffectingthebindingpropertiesof Chineseyam starch(Dioscoreaoppositifolia)have beeninvestigatedincomparisonwithcornstarchu singa2factorialexperimentaldesign.Thefacto rialexperimentaldesignhasbeenfoundusefulinthe analysisofthequantitativeindividualandinteraction effectsofvariousformulationfactorsonthemechani calstrength and drug release propertiesoftab lets7

 Themechanicalpropertiesofthetabletwhichare indicatorsoftheabilityofthetabletstowithstandthe rigorsofhandlinginvolvedinmanufacture,transpor tation,dispensingandusage,hasbeenassessedby twoimportantproperties:bondstrengthandbrittle ness.Thetensilestrengthofatabletisafunc tionoftheareaofcontactbetweentheparticlesand thestrengthofbondsproducedbetweenthem. Thegreaterthedegreeofbonding,thegreateristhe tensilestrengthofthetablets.Thebrittlefracturein dex(BFI)ontheotherhand,wasdevisedbyHies tandetalandisobtainedbycomparingtheten silestrengthofatabletwithaholetothetensile strengthofthetabletswithoutahole,bothatthe samerelativedensity.Theholeservesasabuiltin stressconcentrator"defect".AlowvalueofBFIis

desirablefortheminimizationofcappingandlamina tionduringtabletproduction.

 Chloroquinephosphate,a4aminoquinolineanti malarialcompoundwasusedasthemodeldrug. Chloroquinephosphatecannotbemadeintosatisfac torytabletsbecauseofitspoorcompressionproper tiesandthereforerequiresabinder,amongotherex cipients,toformsatisfactorytablets.

MATERIALSANDMETHODS

ThematerialsusedwerechloroquinephosphateBP andcornstarchBP(BDH ChemicalsLtd.,Poole, U.K.),polyvinylpyrrolidone,PVP Mol.Wt. 44,000(BDHChemicalsLtd.,Poole,U.K.)and tubersofDioscoreaoppositifolia(Chineseyam)ob tainedfromlocalfarmersinIbadan,Nigeriaandau thenticated.Thestarchwasextractedfromthetubers usingestablishedprocedures

Preparationofgranulesandtablets

Batches(200g)ofabasicformulationofchloro quinephosphate(60%w/w),lactose(30%w/w) andcornstarch(10%w/w)weredrymixedfor5 minutesinaplanetarymixer(ModelA120,Hobart ManufacturingCo,U.K)andthenmoistenedwith appropriateamountsofstarchpastetoproducegran ulescontainingdifferentconcentrationsofthestar chesasbinder(2.510%w/w).Massingwascon tinuedfor5minutesandthewetmassesweregranu latedbypassingthem manuallythroughamesh12 sieve(1400μm).Theseweredriedinahotairov enat50℃ for18hours.Driedgranulesweresieved throughamesh16sieve(1000μm)andthen storedinairtightcontainer.Themoisturecontentof thegranuleswasdeterminedandfoundtobebetween 24% w/w.Particledensitiesweredeterminedby thepycnometermethod,usingxyleneasthedis placementfluid.

Preparationoftablets

Quantities(500 mg)ofgranuleswithinthesize rangeof7101000μmwerecompressedfor30sec ondsintotabletswithpredeterminedloadsonaCarv erhydraulicpress(modelC,Carverinc.Menom

oneeFalls,WIS)usinga10.5mm dieandflat facedpuncheslubricatedwitha1% dispersionof magnesiumstearateinacetonebeforeeachcompres sion.Afterejection,thetabletswerestoredoversil icagelfor24hourstoallowforelasticrecoveryand hardening.Theweights(w)anddimensionsofthe

· 2

·

UNIVERSITY OF IBADAN LIBRARY

(3)

29.AsnPacJlofTrlMe     

tabletswerethendeterminedtowithin ±1mgand 0.01mm respectively,andtheirrelativedensities, D,werecalculatedusingtheequation:

D = w/V.ρ (1) whereVisthevolume,cm,ofthetabletincluding theholewhenpresentandρistheparticledensity, gcm,ofthesolidmaterial.

Testing

Thetensilestrengthofthechloroquinephosphate tablets(T)wasdeterminedatroom temperatureby diametralcompressionusing a hardnesstester

(KetanScientific& Chemicals,Ahmedebad,Indi a).Thetensilestrengthofthetabletwasthencalcu latedfromtheequation:

T=2L/πdh (2) whereTistheradialtensilestrength,Listheload neededtobreakthetablet,disthetabletdiameter andhisthetabletthickness.Resultsweretaken onlyfromtabletswhichsplitcleanlyintotwohalves withoutanysignoflamination.Allmeasurements weremadeinquadruplicatesandtheresultsgiven arethemeanofseveraldeterminations.

 Thebrittlefractureindex(BFI)valuesofthetab letswerecalculatedfromtheequation:

BFI=0.5[(T/T)-1] (3) whereTisthetensilestrengthofthetabletwithouta holeandTisthetensilestrengthofatabletwitha hole.

Disintegrationanddissolutiontest

Thedisintegrationtimeofthetabletswasdetermined indistilledwaterat37±0.5℃ usingadisintegra tiontester(VeegoScientificdevices,Mumbai,Ma harashtra,India). Determinationswere done in quadruplicates.

 Dissolutiontestwascarriedoutonthetabletsu singtheUSPXX IIIbasketmethod(HansonModel 72RL,U.S.A)rotatedat100rpm in900mLof 0.1M HCL,maintainedat37±0.5℃.Samples

(5mL)werewithdrawnandreplacedwithequala mountsoffreshmedium.Thesamplewasdiluted andtheamountofchloroquinephosphatereleased wasdeterminedatwavelengthof255nm,usinga UV/visiblespectrophotometer(PhillipsPye Uni

cam,PU 8610 Kinetics,Sarosescientificinstru ments,Cambridge,U.K.).Determinationswere doneintriplicates.

FactorialExperimentalDesign

Afactorialexperimentaldesignwasusedtostudythe effectsofnatureofbinder(denotedbyN),concen trationofbinder(denotedbyC)andrelativedensity

(denotedbyD)onthemechanicalandreleaseprop ertiesofchloroquinephosphatetablets.Thebasis

oftheexperimentaldesignwasthateachofthethree variableswasutilizedata"high"level(denotedby thesubscript,H)anda"low"level(denotedby thesubscript,L).Thenumberofexperimentsinthe designwas2=8.

 Usingtheabovenomenclature,thevariouscombi nationsbetween thevariablesused in thedesign were:

,N,N,N,N,N,N= Natureofbinder(Chineseyamstarch) N= Natureofbinder(cornstarch)

= Concentrationofbinder(2.5%)

= Concentrationofbinder(10%)

= Relativedensityof0.80 D= Relativedensityof0.90

Bygroupingtheresultsintoanumberofsets,itwas possibletoassesstheeffectsthateachofthethree variableshadseparatelyonthemechanicalandre leasepropertiesofthetabletsandalsotodetermine whetherthevariableswereinteractingoractinginde pendentlyofeachother.

 TheeffectsofincreasingN,from its"low"level toits"high"levelonthevariousparameterswere foundbysummingalltheresults(TorBFIorDTor t80)ofsamplescontaining"high"levelofN and subtractingthesumoftheresultsofsamplescontai ning"low"levelsofN.Thatis:

1/4[(N+ N+ N+N

-(N+N+N+N)]

 Theamountbywhichtheresultofthistreatment departedfrom zero,irrespectiveofwhetherpositive ornegativewasaquantitativemeasureoftheeffectof Nonthevaluesoftherelevantparameter.Similar expressionswereusedforfindingtheeffectsofCand D.

  Todeterminewhethertherewasanyinteraction

· 3

·

UNIVERSITY OF IBADAN LIBRARY

(4)

betweentwovariables,theT(orBFIorDTort80) resultsofthecombinationsinwhichtheyappearto getherateither"high" or"low" levelswere summedandthesum ofothercombinationssubtrac tedfromthistoobtaintheinteractioncoefficient.For example,forNandC:

1/4[(N+N+N+N

-(N+N+N+N)]

Aresultofzeroindicatesnointeraction,butifthe interactioncoefficientissignificantlyremovedfrom zero,itcanbeconcludedthatthetwovariablescon cernedareinteractingwitheachother.Theextentof removalfromzeroisameasureofinteraction.Simi larexpressionswereusedforestimatingtheinterac tionbetweenNandD,andbetweenCandD.

Statisticalanalysis

Statisticalanalysiswascarriedoutusingtheanalysis ofvariance(ANOVA)andTukeyKramermultiple comparisontestsonacomputersoftwareGraphPad Prism 4(GraphPad Software Inc. San Diego, USA).

RESULTS

Therepresentativeplotsoflogtensilestrength,brit tlefractureindex(BFI)and disintegration time

(DT)versusrelativedensity(RD)forchloroquine phosphatetabletscontaining10% w/wofthestarch bindingagentsarepresentedinFigures1,2and3 respectively,whilethedissolutionprofilesofthetab letsarepresentedinFigure4.ThevaluesofT,

BFI,DTandt80(thetimerequiredfor80% ofchlo roquinephosphatetobereleased)attwoselected relativedensityvaluesof0.8and0.9,whichare representativeoftherangeofrelativedensityvalues normallyachievedforcommercialchloroquinephos phatetablets,usedforthefactorialexperiment,are presentedinTable1.Thesevalueswereusedtocal culatetheindividualandinteractioncoefficientsfor thevariablesusingtherelevantequations.Theindi vidualandinteractioncoefficientvaluesarepresen tedinTable2.Thesevaluesprovideaclearindica tionofthequantitativeeffectsofthethreevariables studiedonthemechanicalstrengthandthedrugre leasepropertiesofthechloroquinephosphatetab lets.

Tabl1  Teesh()befeix(BFI),

ntmeDT)addntme(80)ofc epetsfrteflemeld

Vasa mb

Te

MNm-2

Br

Di

memi mi

0. 0. 1. 8. 1. 0. 9. 6. 0. 0. 1. 0. 1. 0. 6. 3. 0. 0. 0. 4. 0. 0. 6. 1. 0. 0. 1. 2. 1. 0. 7. 7.

Tabl2 Iladinesofneofshb),cnofshb)adred

),ntemeladdgrepsofcepet Va Tees

MNm-2

Br ei

Di memi

mi

tc -0. 0. -8. -20. 0. -0. 7. 3. 0. -0. 8. 0. <0. P<0. P<0. <0. nc N-C -0. -0. -6. -16. N-D -0. -0. -2. -4. C-D 0. -0. 1. 3.

<0. P<0. P<0. P<0.

· 4

·

UNIVERSITY OF IBADAN LIBRARY

(5)

29.AsnPacJlofTrlMe     

 Incomparingtheformulations,therankingofthe individual(independent)coefficientvaluesforthe formulationsonTwasD >NC,onBFIwasN > DC,onDTwasD >N >Candont80wasC>N

>D whiletherankingoftheinteractioncoefficient onTwasND> CD NC,onBFIwasND > NC =CD,onDTandt80wasNC>ND>CD.

Thereweresignificant(P<0.001)interactionsbe tweenthenatureofbinder,Nandtheothertwovari ables,CandD.

Fiur1PltofLomofTeeshvsr yfrcepetscg10%w/

wofshbrwihh(……)adwitah__

__)attrc■,Cheymsha▲,

DISCUSSION

TheinfluenceofNonT,DTandt80wasnegativein dicatingthatchangingthebindingagentfrom Chi neseyam starchwhichrepresentedthe"low"level tocornstarchwhichrepresentsthe"high",ledtoa decreaseinT,DTandt80butincreaseinBFIofthe tablets.Thus,Chineseyam starchproducedtablets withhighertensilestrengthandlongerdisintegration anddissolutiontimesthanthetabletscontainingcorn starchasbindingagent.TheinfluenceofNonBFI

Fiur2Pltofbefeixvsred rcepetscg10% w/w o ■,Cheymsha▲,ns

Fiur3PltofDintmevsred rcepetscg10% w/w o ■,Cheymsha▲,ns

waspositiveindicatingthatChineseyamstarchbind erproducedtabletswithlowerBFIvaluesthancorn starch.Thisindicatesthatthetabletscontaining Chinesestarchhasbetterabilitytorelievestressand preventcappingandlaminationduringtabletproduc tionthantabletscontainingcornstarch.Thus,Chi neseyamstarchappearstobeastrongerbindinga

· 5

·

UNIVERSITY OF IBADAN LIBRARY

(6)

Fiur4Dinpsofcepet g10% w/wofssasbsatred yof0.■,Ch▲,Co

gentthancornstarch.However,allthetabletscom

pliedwiththeBPrequirementondisintegration

(i.e.disintegrationwithin15minutes)exceptfor mulationscontaining10%w/wChineseyam starch which had a disintegration time of26 minutes. Thus,Chineseyamstarchcouldbemoreusefulasa bindingagentwhenstrongermechanicalproperties andlongerdisintegrationanddissolutiontimeisre quired.

  TheeffectsofCindicatethatincreasingthecon centrationofbinderfrom2.5to10% w/wledtoan increaseinthetensilestrength,disintegrationand dissolutiontimesofthetablet.However,theeffect ofContheBFIwasnegative,indicatingthatthere wasadecreaseinthetabletbrittleness.Ithasbeen shownthattheheatproducedduringcompression wouldcausemeltingoftheasperitiesand ofthe binderswhich on cooling would solidify to form strongsolidbondsbetweentheparticles.Thea

mountofbondingwoulddependontheconcentration ofbindingagentpresent.ThedecreaseinBFIvalues withincreaseinCindicatesthatthepresenceofa binderatinterparticulatepointsfacilitatesplasticde formationforthereliefoflocalizedstresses.Thus, theconcentrationofthestarchbinderhastobecare fullyselectedtoobtaintabletswithadequatestrength and with desired disintegration/dissolution times. Thisisinagreementwiththeresultsofotherwork

ers

 Therelativedensity(D)hadthehighesteffecton tensilestrengthanddisintegrationtimebuttheleast effectondissolutiontime.Thus,increasingtherela tivedensityfrom0.80to0.90ledtoanincreasein T,DTandt80,butadecreaseinBFI.Formost pharmaceuticalmaterial,therelativedensityofthe tabletsgenerallyincreaseswithincreaseincompres sionpressure.Thiswillleadtoadecreaseinporosi tyorreductionincapillarymicrostructureofthetab letsresultingincloserpacking.Thus,moresolid bondswillbeformedbetweentheparticlesleadingto anincreaseinthemechanicalstrengthofthetablets. Particlerearrangement,fragmentationanddeforma tionmayalsoresultintheclosureoftheinterandin tragranularporespaces,therebyreducingthecapil larymicrostructureoftabletsandthereductioninthe sizeofthecapillaryspacesbetweentheparticleswill reducetherateofpenetrationofwater,whichwillin turnleadtoanincreaseindisintegrationanddissolu tiontimes. Thereweresignificant(P<0.01) differencesintheeffectsoftheindividualvariables onthemechanicalandreleasepropertiesofchloro quinephosphatetablets.

 Theinteractioncoefficientvalues(Table2)indi catethatallthevariablesinteractedwitheachother toalterthemechanicalandreleasepropertiesofthe tablets.TheinteractionbetweenN andD hadthe largesteffectonmechanicalpropertiesofthetablets whiletheinteractionbetweenN andChadthelar gesteffectondisintegrationanddissolutiontimesof thetablets.Thus,thenatureandconcentrationof bindingagentusedintabletformulationsneedtobe carefullychoseninordertoobtaintabletsofdesired mechanicalanddrugreleaseproperties.Ingeneral, therewerestatisticallysignificant(P<0.001)in teractionsbetweenthenatureofbinder,N andthe othervariables,CandD.TheeffectofNontablet propertieswereshowntobestronglyrelatedtothe concentrationofthestarchbinder(C)andtherela tivedensityofthetablet(D)employedintheformu lation.Thus,thereappearstobeastronginterac

tionbetweenChineseyam starchandtheotherfor mulation and processing variables. Furthermore, changingthetypeofstarchbinderfromChineseyam starchtocornstarch,andincreasingthebindercon centration(C),led to an increase in tensile strength,disintegrationanddissolutiontimes,buta

· 6

·

UNIVERSITY OF IBADAN LIBRARY

Referencias

Documento similar

puede ser distinta a la titularidad del teléfono celular con el que te “Afiliaste”, por lo que es de tu entera responsabilidad cualquier transacción que realices,