Nonsteroidal anti-inflammatory drugs naproxen (NAP) ((+)-(S)-2-(6-methoxynaphthalen-2-yl) propionic acid) and ketoprofen (KET) (RS)-(2-(3-benzoylphenyl)-propionic acid) were investigated by thermoanalytical techniques (TG/DTG/DTA, DSC and hot-stage microscopy) and evolved gas analysis (TG-FTIR) for evaluating their thermal behavior. In air, TG curve of NAP presented one mass loss step followed by the burning of carbonaceous material, with final residue of 1.5%, while in nitrogen, a single mass loss step was observed. After melting, if the sample is submitted to an isotherm it evaporates. According to DSC curve, NAP melts at 153.5 °C (∆Hfus = 31.6 kJ mol−1; ∆Sfus = 73.5 J K−1 mol−1) and recrystallizes in the cooling step. These events were confirmed by hot-stage microscopy. TG-FTIR studies revealed that NAP decomposes by releasing 2-methoxynaphthalene and propionic acid. Ketoprofen TG curves in both atmospheres presented a single mass loss. When the sample was kept under isotherm, after melting, it evaporated. From DSC data, the melting at 93.3 °C (∆Hfus=28.4 kJ mol−1, ∆Sfus = 76.9 J K−1 mol−1) was observed, without crystallization or cooling.
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Kantor TG. Ketoprofen: a review of its pharmacologic and clinical properties. Pharmacotherapy. 1986;6(3):93–103.
Al-Shammary FJ, Aziz Mian NA, Saleem Mian M. Naproxen. Anal Profiles Drug Subst Excip. 1992;21:345–73.
Giron D. Thermal-analysis and calorimetric methods in the characterization of polymorphs and solvates. Thermochim Acta. 1995;248:1–59.
Giordano F, Novak C, Moyano JR. Thermal analysis of cyclodextrins and their inclusion compounds. Thermochim Acta. 2001;380:123–51.
Valladão DMS, Oliveira LCS, Zuanon Netto J, Ionashiro M. Thermal decomposition of some diuretic agents. J Therm Anal. 1996;46:1291–9.
Ribeiro YA, Oliveira JDS, Leles MIG, Juiz AS, Ionashiro M. Thermal decomposition of some analgesic agents. J Therm Anal. 1996;46:1645–55.
Pinto BV, Ferreira APG, Cavalheiro ETG. A mechanism proposal for fluoxetine thermal decomposition. J Therm Anal Calorim. 2017;130:1553–9.
Ferreira APG, Pinto BV, Cavalheiro ETG. Thermal decomposition investigation of paroxetine and sertraline. J Anal Appl Pyrolysis. 2018;136:232–41.
Pinto MAL, Ambrozini B, Ferreira APG, Cavalheiro ETG. Thermoanalytical studies of carbamazepine: hydration/dehydration, thermal decomposition, and solid phase transitions. Braz J Pharm Sci. 2014;50(4):877–84.
Guinesi LS, Cavalheiro ETG. The use of DSC curves to determine the acetylation degree of chitin/chitosan samples. Thermochim Acta. 2006;444:128–33.
Bannach G, Arcaro R, Ferroni DC, Siqueira AB, Treu Filho O, Ionashiro M, Schnitzler E. Thermoanalytical study of some anti-inflammatory analgesic agents. J Therm Anal Calorim. 2010;102:163–70.
Sovizi MR. Thermal behavior of drugs investigation on decomposition kinetic of naproxen and celecoxib. J Therm Anal Calorim. 2010;102:285–9.
Mura P, Faucci MT, Manderioli A, Bramanti G, Parrini P. Thermal behavior and dissolution properties of naproxen from binary and ternary solid dispersions. Drug Dev Ind Pharm. 1999;25(3):257–64.
Bettinetti G, Bruni G, Giordano F, Mura P. Thermal-analysis of the dehydration process of cross-linked polyvinylpyrrolidone and its mixtures with naproxen. Drug Dev Ind Pharm. 1994;20(14):2215–25.
Bettinetti G, Mura P, Giordano F, Setti M. Thermal behaviour and physicochemical properties of naproxen in mixtures with polyvinylpyrrolidone. Thermochim Acta. 1992;199:165–71.
Bannach G, Schnitzler E, Treu Filho O, Utuni VHS, Ionashiro M. Synthesis, characterization and thermal studies on solid compounds of 2 chlorobenzylidenepyruvate of heavier trivalent lanthanides and yttrium(III). J Therm Anal Calorim. 2006;83:233–40.
Tiţa D, Fuliaş A, Tiţa B. Thermal stability of ketoprofen. J Therm Anal Calorim. 2013;111:1979–85.
Tiţa D, Fuliaş A, Tiţa B. Thermal stability of ketoprofen—active substance and tablets. J Therm Anal Calorim. 2011;105:501–8.
Oliveira LJ, Stofella NCF, Veiga A, Férdele S, Toledo MGT, Bernardi LS, Oliveira PR, Carvalho Filho MAS, Andreazza IF, Murakami FS. Physical–chemical characterization studies of ketoprofen for orodispersible tablets. J Therm Anal Calorim. 2018;133:1521–33.
Mura P, Mandersioli A, Bramanti G, Furlanetto S, Pinzauti S. Utilization of differential scanning calorimetry as a screening technique to determine the compatibility of ketoprofen with excipients. Int J Pharm. 1995;119:71–9.
NIST Standard Reference Data Program collection (C) 2018 copyright by the U.S. Secretary of Commerceon behalf of the United States of America. All rights reserved. Sadtler Research Labs Under US-EPA Contract.
Nicolet-ThermoScientific Co. Nicolet EPA vapor phase data-base. Omnic 8.0 software. ThermoScientific, Madison.
The authors thank FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, Grant No. 2017/04211-7) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for financial support.
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Medeiros, R.S., Ferreira, A.P.G. & Cavalheiro, E.T.G. Thermal behavior of naproxen and ketoprofen nonsteroidal anti-inflammatory drugs. J Therm Anal Calorim 142, 849–859 (2020). https://doi.org/10.1007/s10973-020-09389-1
- Evolved gas analysis
- Thermal behavior