rapid shelf life estimation using non-isothermal

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).