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Rapid shelf life estimation using non-isothermal treatments by DSC
AndreaARTEAGA-ROBALINO1,RobertALCOCER-VALLEJO1,JavierSANTAMARÍA-AGUIRRE1andLuisCASTILLO-CABAY1
1UniversidadCentraldelEcuador.andrearteagar_20@hotmail.com,jrsantamaria@uce.edu.ec
Arteaga, A. (2017). Estimación rápida del tiempo de vida útil del ácido acetilsalicílico mediante tratamientos no isotermales empleando calorimetríadiferencialdebarrido.Quito:UniversidadCentraldelEcuador.
ThisprojectwaspossiblebythesupportfromProyectoSemillaofUniversidadCentraldelEcuadorandAcadémiedeRechercheetD ̓̓ EnseignementSupérieur(ARES)fromBelgium.
The traditionalmethods fordetermining theshelf lifeofdrugsare isothermal, they require longperiodsof time for theirexecutionanddonotconsider the kinetics of the solid state. Thedynamicsof industrial production require that decisions regarding stability shouldbe takenquicklywithoutneglectingthesafety,efficacyandqualityinherentinmedicines.Therefore,rapid,sensitiveandsafemethodsareneededtoestimatetheshelflifeofrawmaterialsandpharmaceuticalforms.Theuseofnon-isothermaltechniques,likedifferentialscanningcalorimetry(DSC),reducethetimerequiredfortheassay,frommonthsoryears,toafewdays.
Mainobjective:Estimatetheshelflifeofacetylsalicylicacid(ASA)manufacturedindifferentyearsandASA/salicylicacid(SA)binarymixturesusingDSCandtheKissingermethod.
§ Preexponential factor and activation energy, calculated withthe Kissinger equation, for the raw material and the binarymixtures show there is not significant difference betweenthem.So,thesesamplescanbecharacterizedbyanisokineticpoint where the degradation kinetic is the same for all.Besides,theremainingshelf lifechangeswithspecificsurfaceareabecauseparticleswithlessareaavailableforthereactiondegrademoreslowlythantheotherones.
§ Theusednon-isothermalmethodisafasttoolfortheshelflifeestimation and it is sensitive enough to detect activationenergy differences possibly related to variations incomposition,productionprocessorstorage.
Introduction
RawmaterialandbinarymixturesanalyzedbyHPLC QuantificationofASA
DSCAssay
Heatingrate(β):5,10,20°C/min
Tm
Kissingermethod
MicroscopicAssay
𝑙𝑛 #𝛽𝑇𝑚2( = 𝑙𝑛 *
𝐴𝑅𝐸𝑎/ −
𝐸𝑎𝑅𝑇𝑚
𝑏 = −𝐸𝑎 𝑅⁄ 𝑎 = 𝑙𝑛 (AR 𝐸𝑎⁄ )
Temperaturerange:90–300°CAtmosphere:NitrogenFlow:25mL/min
Figure1.DSCthermogramsofASA
Figure2.Kissingerplot
ASA/SA binary mixtures were prepared to simulate a natural degradationdegreeandtocomparewiththerawmaterialsresultsobtainedbyDSC.Themaximum reaction temperature (Tm) depends to the heating rate, thissignificanteffectisusedbyKissingerequationtocalculatekineticparameterslikepreexponentialfactor(A)andactivationenergy(Ea).
RM1 RM2 RM3 Mixture1 Mixture2 Mixture3
Activationenergy [KJ/mol] 107,43±5,38 118,57±2,12 112,54±14,39 95,67±6,51 125,41±10,35 102,91±9,99
Pre-exponentialfactor [min-1] 1,29x1012 2,46x1013 5,98x1012 5,38x1010 1,48x1014 3,84x1011
Degradationconstant(25°C) [min-1] 1,94x10-7 4,15x10-8 1,15x10-7 9,32x10-7 1,58x10-8 3,59x10-7
Remainingshelflife,t95 [months] 2,73 14,14 2,71 0,96 33,69 2,54
Table1.Degradationkineticparameters
Figure3.ASAcrystals:(a)RM1;(b)RM2and(c)RM3
A1,mm2 V2,mm3 SSA3,mm-1RM1 1,58 0,099 17,85RM2 1,88 0,139 15,99RM3 1,58 0,100 17,20
1Area,2Volume,3SpecificSurfaceArea
Table2.SpecificSurfaceAreaofASA
Methods Results
Conclusions
References
SAsolutionsprinkledoverASAcrystals
Kissingerequation:
Preparationofbinarymixtures
Tm
EaandAcharacterizethedegradationkineticsofeachsampleandtheyareused to get the degradation constant (K) from Arrhenius equation. Theremainingshelflife(t)toreachadegradation(D)of5%iscalculatedwiththeparametersbelowbythefollowingequation:
𝑡𝐷 =−𝑙𝑛 '1 − 𝐷
100*
𝐴𝑒−𝐸𝑎𝑅𝑇
Toestablisha relationshipbetweenkineticparametersof theASAnaturallydegradedandtheartificialmixtures,theactivationenergieswerecomparedbysimpleANOVAandthereisnostatisticallysignificantdifferencebetweenthem.ThecomplexbehavioroftheASAkineticinvolvedphysicalprocessesrelatedtotheshapeandtheparticlesizeofthesamples.So,thespecificsurfaceareawasdeterminedtoexplainthedegradationlevel(Table2).
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