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Carbohydrate
Polymers
j our na l h o me p ag e : w w w . e l s e v i e r . c o m / l o c a t e / c a r b p o l
Blends
of
cross-linked
high
amylose
starch/pectin
loaded
with
diclofenac
Grazielle
Arantes
Soares, Ana
Dóris
de
Castro, Beatriz
S.F.
Cury, Raul
C.
Evangelista
∗FaculdadedeCiênciasFarmacêuticas,DepartamentodeFármacoseMedicamentos,UniversidadeEstadualPaulista– UNESP,RodoviaAraraquara-Jaú,km1,CEP14801-902, Araraquara,SP,Brazil
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r
t
i
c
l
e
i
n
f
o
Articlehistory: Received14March2012
Receivedinrevisedform3July2012 Accepted3August2012
Available online 10 August 2012
Keywords: Pectin
Highamylosestarch Polymerblends Rheology Thermalanalysis X-raydiffraction
a
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s
t
r
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c
t
Polymersblendsrepresentanimportantapproachtoobtainmaterialswithmodulatedpropertiesto reachdifferentanddesiredpropertiesindesigningdrugdeliverysystemsinordertofulfilltherapeutic needs.Theaimofthisworkwastoevaluatetheinfluenceofdrugloadingandpolymerratioonthe physicochemicalpropertiesofmicroparticlesofcross-linkedhighamylosestarch–pectinblendsloaded withdiclofenacforfurtherapplicationincontrolleddrugdeliverysystems.ThermalanalysisandX-ray diffractogramsevidencedtheoccurrenceofdrug–polymerinteractionsandtheformerpointedalsoto anincreaseinthermalstabilityduetodrugloading.Therheologicalpropertiesdemonstratedthatdrug loadingresultedinformationofweakergelswhiletheincreaseofpectinratiocontributestoorigin strongerstructures.
© 2012 Elsevier Ltd. All rights reserved.
1. Introduction
Drug delivery is a broad field of research in the pharma-ceuticalsciences, forwhichthedevelopmentofnovelmaterials suitabletoaidincontrollingthedrugreleaseaccordingto ther-apeutic needsplays an importantrole. In this sense,blends of alreadyknownpolymersrepresentarationalapproachtoobtain materials with differentand modulated properties that enable theirusefor specificgoals(Carbinatto,Castro,Cury,Magalhães, &Evangelista, 2012; Ebube &Jones, 2004; Lecomte, Siepmann, Walther,MacRae,&Bodmeier,2005;Patel&Patel,2007;Prezotti, Meneguin,Evangelista,&Cury,2012;Wang,Hu,Du,&Kennedy, 2010). This approach can be advantageous, since apart from workingwithwellknownsubstances, itavoidsthehighcostof synthesizingnewmaterials.Additionally,thechangesinpolymer ratiocanresultinawiderangeofphysicochemicalpropertiesthat shouldprovidedifferent drugdeliverypatterns(Lecomte etal., 2005).Starchisoneofthemostabundantavailablepolymersand can beobtained froma variety of sources. It is constituted by amylose,representingthelinearfractionof themacromolecule, whileamylopectinisthehighlybranchedfraction.Highamylose, amodifiedstarchcontaining70%ofamylose,hasbeenreported as possessing improvedproperties for controlled drug delivery purposes in relationto conventional starch (Onofre, Wanga, &
∗Correspondingauthor.Tel.:+551633016976;fax:+551633016960. E-mailaddresses:[email protected],
[email protected](R.C.Evangelista).
Mauromoustkos,2009;Rioux,Ispas-Szabo,Aït-Kadi,Mateescu,& Juhász,2002).Moreover,chemicalreactions(esterification, ether-ification,oxidation)ofhydroxylgroupsofhighamylosestarchcan beusefultomodulatesomeofitscharacteristics,suchassolubility, swelling,rheologicalproperties,filmformationandbiodegradation rate(Riouxetal.,2002).
Cross-linking has been shown to be a key technique for modifying the properties of starches and can be achieved by addingintra-andintermolecularbonds(Singh,Kaur,&McCarthy, 2007).Sodiumtrimetaphosphate(STMP),monosodiumphosphate, sodium tripolyphosphate,epichlorohydrin, phosphorylchloride, a mixtureof adipicacid and acetic anhydride, and vinyl chlo-ridearethemainagents usedtocross-linkfoodgradestarches (Wattanchant,Muhammad,Hashim,&Rahman,2003;Woo&Seib, 1997;Yeh&Yeh,1993).Highamylosecontentscombinedto physi-calandchemicalmodificationsofthismaterialresult,forexample, inproductswithhigherviscosityandingranulesthataremore resistantagainstswelling(Richardson,Jeffcoat,&Shi,2000;Van Hung,Maeda,&Morita,2006).
Many researchers have demonstrated the successful use of highamylosestarchescross-linked bydifferentchemicals,such asepichlorohydrin andSTMP,in thedevelopmentof controlled drugdeliverysystems(Cury,Castro,Klein,&Evangelista,2009a; Cury,Castro,Klein,&Evangelista,2009b;Fangetal.,2008;Lenaerts, Dumoulin,&Mateescu,1991;Lietal.,2009;O’Brien,Wang,Vervaet, &Remon,2009).
Pectins are a family of complex polysaccharides constituted mainlyoflinearlyconnected␣-(1-4)-d-galacturonicacidresidues partiallyesterifiedwithmethanol.Thedegreeofmethoxylation
136 91 (2013) 135–142
(DM)isusedtoclassifypectinsashighmethoxylpectins(DM>50) and low methoxylpectins (DM<50) (Ghaffari, Navaee,Oskoui, BayatiI, & Rafiee-Tehrani, 2007; Lutz, Aserin, Wicker, & Garti, 2009).They are widelyused in thepharmaceuticalindustry to composehydrophilic matrices inoral controlledrelease dosage forms (Sungthongieen,Sriamornsak, Pitaksuteepong, Somsiri, & Puttipipatkhachorn,2004;Wei,Sun,Wu,Yin,&Wu,2006).
In this work, two polymers with different properties were blendedandsubmittedtocross-linkingprocessinordertoprepare materialswithdistinctproperties.Theinfluenceofdrug incorpora-tiononthesepropertieswasevaluatedbyincorporatingdiclofenac inthepolymermicroparticles.
2. Materialsandmethods
2.1. Materials
Pectin(typeLM-506CS,lot:S74431)wasprovidedbyCPKelko (Copenhagen, Denmark), high amylose starch (Hylon VII, lot: HA9140)was obtained fromNational Starch & Chemical (New Jersey,EUA),sodiumtrimetaphosphate(lot:112K1365)was pur-chasedfromSigma–AldrichCo.(St.Louis,USA),sodiumhydroxide (lot: 611648)was suppliedby GrupoQuímica (Riode Janeiro, Brazil),37%hydrochloricacid(lot:29957)wasprovidedbyQuimis (Diadema,Brazil),ethylalcohol(lot:127698)wasobtainedfrom Synth(Diadema,Brazil),andsodiumdiclofenac(lot:061117-1)was providedbyHenrifarma(SãoPaulo,Brazil).
2.2. Cross-linkingreaction
Thecross-linkingreactionofpolymersblendsatdifferentratios (4:1,1:1and1:4)wasperformedinalkalineaqueousmediaand STMPwasusedascross-linker,basedonproceduredescribedby Carbinattoetal.(2012)withminormodifications.Briefly,the poly-mersblends(5%)weredispersedinpre-heatedwaterat80◦Cby mechanicalstirringuntiltoreachroomtemperature.Thebase(4% ofNaOHpellets)wasthenaddedtothedispersionandcompletely dissolvedpriortheadditionofthesolidcross-linker(30%of poly-mermass).Afterthedispersionwaskeptunderstirringfor2h, 3molL−1HCl(about2%,v/v)wasaddedinordertoadjustthepHto 6andtostopthereaction.Thesampleswerewashedoncewith85% ethanol,theneighttimeswith65%ethanolandfinallyoncewith absoluteethanolandfilteredundervacuum.
ThesampleswerelabeledaccordingtopolymersnamesHA–P (highamylose–pectin)followedbytheirrespectiveratiosinthe mixture.Thephysicalmixtures wereindicatedbytheprefixPM whilethesuffixWDandCDdescribethesampleswithout cross-linkerandthesamplescontainingdiclofenac(SD),respectively.
2.3. Drugloading/effectofSDconcentrationondrugloading
Diclofenac was incorporated into the cross-linked samples bysoakingthemintodrugsolutions atdifferentconcentrations (3mg/mL,6mg/mL,9mg/mL),understirringfor30minatroom temperature.After that,the sampleswere frozenand dried by lyophilizationovernight(−30◦C),since,accordingtoprevioustests, theoven-dryingwasnotabletoyieldpowderyproduct.Thedrug contentandefficiencyofincorporationwerecalculatedaccording toEqs.(1)–(3).Thesamplespreparedfrom9mg/mLdrugsolutions wereselectedforthisstudybecausetheyledtohigherefficiencyof incorporation.
2.4. DeterminationofSDcontentofthemicroparticles
Anaccuratelyweighedmassofmicroparticles(about1g)was addedto50mLofwater and thedispersionwasstirredduring
48h.Theproductswerethencentrifugedat3500rpmfor70min and theSD concentrationin thesupernatantwasquantifiedby UVabsorptionat276nmonspectrophotometer(HewlettPackard, Mod.8453).Theanalyseswereperformedintriplicateandthedrug contentwascalculatedaccordingtothefollowingequation.
DC(%)=Aq
Ai ×100 (1)
whereDC(%)is thedrugcontent(%);Aq istheamountofdrug quantifiedinthesampleandAiistheinitialamountofdrugadded tothesample.
2.5. Efficiencyofincorporation
ForthedeterminationoftheamountofSDentrappedintothe particles,10mLofethanolwereaddedtoanaccuratelyweighed massofdrug-containingmicroparticles(about1g),stirredfor5min andfiltered.Thedrugalcoholicsolutionwasevaporatedatroom temperaturetodrynessandtheresiduewasredispersedin25mL ofpurifiedwater.Thisdispersionwaskeptundermagnetic stir-ring(30min)forcompletedrugdissolution.Thedrugconcentration inthesupernatantwasquantifiedbyUVabsorptionat276nmon spectrophotometer(HewlettPackard,Mod.8453)andassumedas freedrug.Thetestswereperformedintriplicateandtheefficiency ofincorporationwascalculatedaccordingtoEqs.(2)and(3).
FD(%)= Aq Ai ×
100 (2)
EI(%)=100−FD (3)
FD(%)isthefreedrug(%),Aqistheamountofdrugquantifiedin thesampleandAiinitialamountofdrugaddedtothesample.EI (%)istheefficiencyofincorporation.
2.6. Sizeandshapeproperties
Particlesizedistributionandshapeofsampleswereanalyzed withaMoticImagesAdvance3.2imageanalyzercoupledtoaLeica MZAPOTMstereoscope,bymeasuringFeret’sdiametersat0◦and circularityofatleast300particlesat32-foldmagnification.
2.7. Thermoanalysis
2.7.1. Thermogravimetricanalysis(TG)anddifferential thermogravimetricanalysis(DTG)
TGandDTGcurvesofsamplesSD,HA-P4:1WD,HA-P4:1CD, HA-P1:1WD,HA-P1:1CD,HA-P1:4WDandHA-P1:4CDwere recordedwithaTAInstruments(SDT600)undernitrogen atmo-sphereatheating rateof10◦C/minbetween25and 1200◦Cfor 5mgofsamplessealedinaluminapans.
2.7.2. Differentialscanningcalorimetry(DSC)
DSCcurvesofsamplesSD,HA-P4:1WD,HA-P4:1CD,HA-P 1:1WD,HA-P1:1CD,HA-P1:4WD,HA-P1:4CD,PMHA-P4:1 WDandPMHA-P1:4WDwereregisteredinaTAInstrumentsDSC 2910atheatingrateof10◦C/minbetween25and600◦C,under nitrogenatmosphere(100mL/min).About5mgofsamplessealed inaluminapanwasusedforeachmeasure.
2.8. X-raydiffraction
91 (2013) 135–142 137
Fig.1. Sizedistributionofsamples.
at40kVand30mA).Thescanningregionswerecollectedfrom4◦ to60◦(2)instepsizeof0.05(2).
2.9. Rheologicalmeasurements
Polymersaqueousdispersions(10%)werepreparedandtheir dynamicviscoelasticpropertiesweremeasuredbyusinga con-trolledstressrheometer(Haake Rheostress1)(GebruderHaake, Germany)equippedwithcone-plate(C35/2Ti)of35mm diame-terandagapof105m.Acirculatingwaterbath(HAAKEC25P) forsampletemperaturecontrol andasoftware (Rheowin3)for dataacquisitionwereused.Allmeasurementswere carriedout intriplicate,withinthelinearviscoelasticrange,at37◦C.Inorder todeterminethelinearviscoelasticregion,stresssweepsbetween 0.1and100Pawereperformed,atalowfrequency(1Hz).Small deformationoscillatoryexperimentswereconductedbyusingtwo stepsofrheologicalmeasurements:(1)frequencysweepsata con-stantstress(1Pa)andangularvelocityrangeof0.6to623rad/sto obtainmechanicalspectrabyrecordingthedynamicmoduliG′and
G′′and(2)creep/recoverytestswerecarriedoutatconstantstress (1Pa).Inthisassaythestresswasappliedinstantlyandmaintained foraperiodof150s.Afterremovingthestress,compliancewas measuredduringfurther150s.
3. Resultsanddiscussion
3.1. Drugloadingandefficiencyofincorporation
Thedrugloadingwasnotsignificantlyinfluencedbyboth poly-merratio and drugconcentrationinsolution,since allsamples presentinghighdruglevel(92–98%).However,thehighest effi-ciencyofincorporationofSDintomicroparticleswasobtainedfrom 9mg/mLSDsolutions,whichwerethenselectedforthepreparation ofsamplesforfurtheranalysis.
3.2. Sizeandshapeproperties
Drugincorporation ledtoa decreasingofparticlesize,since CDsamplespresentedahighestpercentageofparticlesin small-estsizeranges,ascanbeseeninsizedistributionprofiles(Fig.1). Thisbehaviorindicatesthatdrugincorporationresultedinamore packed network due to drug–polymer interactions. The Feret’s diameterestablishesaquantitativeanalysisofparticlesizeandis definedasthedistancebetweentwoparalleltangentsofthe parti-cleatanarbitraryangle(Boschetto&Giordano,2012).Theiraverage values(Table1)confirmedthetendencyofdecreaseofsizedueto thedrugaddition.
Table1
AverageFeretdiameter,circularityandresidualmass(%)ofsamples.
Samples Diameter(m) Circularity Residualmass(%)
HA-P4:1WD 69.16±21.353 0.730±0.0524 45.76 HA-P4:1CD 45.78±21.387 0.716±0.0625 53.74 HA-P1:1WD 61.92±19.788 0.756±0.0426 45.50 HA-P1:1CD 45.03±20.902 0.704±0.0552 47.27 HA-P1:4WD 69.41±21.069 0.742±0.0471 35.19 HA-P1:4CD 42.61±18.558 0.720±0.0539 35.52
Circularityisatwo-dimensionalgeometrictolerancethat con-trolshowmuchafeaturecandeviatefromaperfectcircledefined bythevalue1(Jonesetal.,2008).Thehighcircularityofthe sam-ples,0.704and0.756(Table1),andthenarrowvariationbetween thevaluesdemonstratetheirshaperegularity(Goyanes,Souto,& Martínez-Pacheco,2011;Tunón,Börjesson,Frenning,&Alderborn, 2003).
3.3. Thermoanalyses
TGandDTGcurvesofSD(Fig.2)showaninitialpeakat65◦C, which should be related to moisture evaporation (Bartolomei, Rodomonte,Antoniella,Minelli,&Bertocchi,2007).Asecondand mainpeak(about30%ofmassloss)occursinthreestepsamong 270–375◦C andit can beattributedtoSD melting and decom-position (Sipos, Szücs, Szabó, Er ˝os, & Szabó-Révész,2008).The TG/DTGcurvesofsamplesHA-P4:1WD,HA-P4:1CD,HA-P1:1 WD, HA-P1:1CD, HA-P1:4 WD,HA-P 1:4CD (Fig.2)show a first peak about 40–110◦C attributed to moisture evaporation, asithasbeenreportedforotherspolysaccharides(Einhorn-Stoll, Kunzek,&Dongowski,2007;Godeck,Kunzek,&Kabbert,2001;Shi &Gunasekaran,2008).Themainpeakwasobservedbetween180 and400◦Candtherelativeintensityofthispeakwashigherfor samplesCDthanforsamplesWD,suggestingtheoccurrenceofboth polymerdegradationanddrugmelting,sincetheseeventsoccurin thesametemperaturerangeandprobablyareintegrated.TheCD thermogramsshowedadiscreteshoulderbetween210and220◦C thatindicatesthedecompositionofmorethanonesubstance.The presenceofthisshoulderunchangedinthethermoanalyticalprofile onceagainsuggestsphysicochemicalinteractions betweendrug andpolymer(Mora,Longhi,&Granero,2010).
Sample1:4WD(Fig.2)showsapeakat134◦C,whichcanresult fromlossofchemical bondedwater(Shi&Gunasekaran,2008). Thepresenceofthiseventonlyinthissamplecanbeattributedto thehigherproportionofpectin,whichisthemostcrystalline poly-mer.Anotherpeakabove900◦Ccanbeobservedinthermograms ofsamplesWD,indicatingthatthedrugincorporationpromoted theincreaseofthermalstability,afactthatisconfirmedbyhigher residualmass(%)ofsamplesCD(Table1).Thedrug–polymer inter-actionshouldhavealsoimprovedthermalstabilityofSD,sinceits decompositionpeak at800◦Cisnot presentinthermogramsof CDsamples.Theoverallmodificationsinthermalbehaviorof sam-plesWDandCDshouldbeattributedtothestructuraldifferences promotedbydrug–polymerinteractions.
138 91 (2013) 135–142
Fig.2.Thermogravimetricanalysis(TG/DTG)ofsamples.
200◦C,shouldbeattributedtodepolymerizationofpectinchains, whichis confirmedbythehighest intensityofthis peak inthe samplewiththegreatestpectinamount(PMHA-P1:4)( Einhorn-Stoll et al., 2007; Shi & Gunasekaran, 2008). The third peak above244◦Cisattributedtothehighamylosestarchdegradation (Massicotte,Baille,&Mateescu,2008).
TheDSCcurvesofsamplesWDandCD(Fig.3)showed simi-larprofiles;nevertheless,samplesCDshowedadecreaseofTmof polymerinrelationtosamplesWD.Inaddition,theendothermic andexothermicpeaksofdiclofenacareabsentinCDsamples.Both eventsindicatethatSDismolecularlydispersedwithinthepolymer matrix,buildingasolidsolution(Siposetal.,2008).
ThechangeintheTmofthepolymershouldalsobeattributed tomorphological modificationsexperiencedbypolymer matrix, suchasthesizeofcrystallitesandthecrystallinitydegreedueto drug–polymerinteractions(Devineetal.,2006).
3.4. X-raydiffraction
Thediffractogrampatternsofsamples(SD,HA,P,HA-P4:1WD, HA-P4:1CD,HA-P1:1WD,HA-P1:1CD,HA-P1:4WD,HA-P1:4 CD)areexhibitedinFig.4.Thehighamylosestarch(HYLONVII®) diffractogramshowscharacteristicpeaksofBstructurearound17◦, 19◦,23◦and25◦(2)(Freire,Fertig,Podczeck,Veiga,&Sousa,2009; Mishra,Datt,&Banthia,2008).Thepectindiffractogrampresents intenseandwelldefinedpeaksat12.7◦,18.42◦,25.32◦and40.14◦ (2),showingitscrystallinestructure(Mishraetal.,2008).
ForallHA–PmixingratiosinWDmicroparticles,the character-isticpeaksofhighamylosestarchandpectinareabsent,behavior that canbe attributedtothe amorphization of samplesdue to thelyophilization process(Mora etal., 2010)and tothe struc-turalreorganizationpromotedbythecross-linkingreaction.The SDdiffractogram exhibitssignificantpeakscharacteristicof this drugaround15.39◦,17.42◦and27.24◦ (2)(Fini,Moyano,Ginés,
Martinez-Perez,&Rabasco,2005).ThedisappearanceofSDpeaksin CDmicroparticles,mainlyatlowvaluesof2,shouldberesultfrom thedestructionofthecrystallinestructure,whichinvolveschanges inbothcrystallitessizeandcrystallinitydegree(Devineetal.,2006). Thesemorphologicalchangescanoccurduetoprogressive amor-phizationand/ordissolutionofthedruginsidethepolymermatrix, sincedrugmoleculesinteractwithpolymeranditsoriginal crys-tallinestructurebecomesdeformed(Finietal.,2005).Thesetof X-raydiffractionresultsreinforcetheoccurrenceofdrug–polymer interactions,asindicatedbythermalanalysisdata.
3.5. Rheologicalproperties
Themechanicalspectradatacanbeusedtoclassifythestructure ofgelsasweakorstrong(Martínez-Ruvalcaba,Chornet,&Rodrigue, 2007).ThemechanicalspectraofWDandCDmicroparticlesare showninFig.5,inwhichitcanbeobservedthatG′valuesremained higherthanG′′valueswithinthewholefrequencyrangeexplored andthevalueswerequasiparallel,displayingtheelasticgel behav-iorofallmaterials.Inaddition,bothsamplesWDandCDbehaved asstrongortruegel,characteristicofcovalentlycross-linked net-works,sinceG′valueswerenearlyfrequencyindependent(Grassi, Lapasin,Grassi,&Colombo,2006;Martínez-Ruvalcabaetal.,2007; Rosalina&Bhattacharya,2002;Szütsetal.,2010;Yoneya,Ishibashi, Hironaka,&Yamamoto,2003).
91 (2013) 135–142 139
Fig.3. DSCcurvesofsamples.
the original H bond formation between them. Similar behav-ior was related for PAA/PVA hydrogel containing aspirin (Mac Gann, Higginbotham, Geever, & Nugent, 2009) and protein-polysaccharidesystemscontainingsalbutamol(Saxena,Kaloti,& Bohidar,2011).Thisweakeningofnetworkbydrugincorporation isrelatedtoa“plasticizingeffect”ofthedrugthatdisturbs macro-molecularinteractionsofgelnetwork(Franc¸ois,Rojas,Daraio,& Bernik,2003).
Thevariationofstoragemodulus(G′)atlowfrequenciesina log–logplotofG′ versusωfollowsthepowerlaw(Saxenaetal., 2011),givenby:
G′=Sωn (4)
whereG′isthestoragemodulus;Sthegelstrength;ωtheoscillation frequencyandnistheviscoelasticexponent.
The n and S values have shown to be sensitive to the cross-linking density within the polymer network, allowing a quantitative estimation of strength of gel structures (Nyström, Walderhaug,Hansen,&Lindman,1995; Scalan&Winter, 1991;
Watase, Nishinari,&Clark,1989).In thissense,thedecreaseof distanceisrepresentedbyhigherSvaluesandanincreaseofthe cross-linkingdensity,botheventsrelatedtostrongergelstructures. Inversely, thedecreaseofn exponentvalues withincreasingof cross-linkingdensitywasreportedinastudywithPVAgels(Morris, Rees,Thom,&Welsh,1977).
Analogously,samplesWDbuiltstrongergels,accordingtotheir lowvaluesofnandhighestvaluesofS(Table2),whilesamples CD shouldresultin alooser andweaker structure. Besides,the
Table2
G′,R(%),nexponentandSvaluesofsamples.
Samples G′(Pa) %R n S
HA-P4:1WD 105.21 48.15 0.058 92.94
HA-P4:1CD 9.67 11.77 0.358 4.75
HA-P1:1WD 353.36 41.75 0.154 282.47
HA-P1:1CD 72.74 30.50 0.185 51.10
HA-P1:4WD 1467.00 73.52 0.142 1095.97
140 91 (2013) 135–142
Fig.4. X-raydiffractionpatternsofsamples.
sample1:4HA-PWDexhibitedthehighestSvalues,whichmust beattributedtothestrongeststructuresthatareclosesttocovalent gels.
Thesefindingsareinagreementwithmechanicalspectradata thatindicatethatthedrugincorporationresultedintheweakening ofpolymernetworkduetofactorspreviouslydiscussed.
Thecreep-recoverytestswereperformedtoassistthe under-standingoftheinternalstructuresofthesesystemsthatpresented an important elastic behavior as showed by mechanical spec-tra. The recovery(%) was calculated from Jmax and Jmin values
(Table 2), according to an equation proposed by Ghannam (2004):
R(%)=
Jmax−J min Jmax×100 (5)
91 (2013) 135–142 141
Fig.5.Mechanicalspectraofsamples.
forsamplesWDandCDshowthatinternalstructuresaredifferent (Dolz,Hernandez,&Delegido,2008),whichalsoshouldberelated todrug–polymerinteractions.
4. Conclusions
The influence of both drug loading and polymer propor-tion on microparticles properties was demonstrated and the drug–polymerinteractionswereevidencedbytheanalyticalresults presentedinthiswork.Inaddition,itwasdemonstratedthatthe drugloadingresultedinanincreaseofboththermalstabilityand crystallinitydegree,butwithadecreaseofmechanicalstrengthof thestructures.Likewise,themicroparticlespropertieswere sensi-tivetopolymerproportion,sincetheblendswithhigherlevelsof pectinresultedinhigherthermal stability,whiletherheological properties,generally,pointedtothestrengtheningof the struc-tures.
Acknowledgments
The financial support provided by Coordenac¸ão de Aperfeic¸oamento de Pessoal de Nível Superior (CAPES) and Fundac¸ãodeAmparoàPesquisadoEstadodeSãoPaulo(FAPESP) isacknowledged.
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