Advertisement

Journal of Thermal Analysis and Calorimetry

, Volume 133, Issue 3, pp 1521–1533 | Cite as

Physical–chemical characterization studies of ketoprofen for orodispersible tablets

  • Laiane J. Oliveira
  • Nayana C. F. Stofella
  • Andressa Veiga
  • Suélyn Féderle
  • Maria da Graça T. Toledo
  • Larissa S. Bernardi
  • Paulo R. Oliveira
  • Marco Aurélio S. Carvalho Filho
  • Itamar F. Andreazza
  • Fábio S. Murakami
Article
  • 119 Downloads

Abstract

The development of orodispersible tablets containing ketoprofen (KTP) offers versatility in administration to patients with swallowing difficulties. The rational development of a medication requires characterization studies for the solid state of the active ingredient and compatibility with excipients to thus ensure a high-quality, safe and effective pharmaceutical form. Therefore, compatibility studies were performed by differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG), spectroscopy techniques (DRIFT, DRX, Raman), and morphological analysis by scanning electron microscopy in order to obtain thermal characterization of the drug. The DSC curve demonstrated an endothermic, symmetrical and evident fusion event (Tpeak = 96.37 °C, ΔH = −120.92 J g−1) and the TG/DTG curve showed mass loss of Δm = 92.45% relative decomposition. For stability analysis, the non-isothermal kinetic study was carried out. The granulate KTP showed higher Ea = 77.30 ± 0.25 kJ mol−1, hence being more stable than pure KTP (Ea = 54.69 ± 1.53 kJ mol−1). Regarding the compatibility study, a displacement of the drug’s melting point to lower temperatures was observed. However, a more significant interaction was evident with magnesium stearate. Further studies were performed using spectroscopic techniques of DRIFT, Raman, X-ray diffraction and by scanning electron microscopy, which demonstrated that there was no change in physicochemical properties of pure KTP. Therefore, through this study it is possible to produce orodispersible tablets by compression and freeze-drying methods containing ketoprofen.

Keywords

Ketoprofen Orodispersible tablets Kinetics analysis Compatibility studies Solid-state interactions 

Notes

Acknowledgements

The authors would like to thank the Brazilian National Research Council (CNPq) by their financial support and the Academic Publishing Advisory Center (CAPA) of Federal University of Parana for assistance with English language editing.

References

  1. 1.
    Rençber S, Karavana Y, Özyazici M. Bioavailability file: ketoprofen. J Pharm Sci. 2009;34:203–16.Google Scholar
  2. 2.
    United States Pharmacopeia and National Formulary (USP 32 - NF 27). Rockville: United States Pharmacopeia Convention; 2009, p. 2739.Google Scholar
  3. 3.
    BRASIL. Agência Nacional de Vigilância Sanitária (ANVISA). Farmacopeia Brasileira. 5th ed. Distrito Federal Brasília: Agência Nacional de Vigilância Sanitária (ANVISA); 2010.Google Scholar
  4. 4.
    Asensio C, Levoin N, Guillaume C, Guerquin MJ, Rouguieg K, Chrétien F, Chapleur Y, Netter P, Minn A, Lapicque F. Irreversible inhibition of glucose-6-phosphate dehydrogenase by the coenzyme A conjugate of ketoprofen: a key to oxidative stress induced by non-steroidal anti-inflammatory drugs? Biochem Pharmacol. 2007;73(3):405–16.CrossRefGoogle Scholar
  5. 5.
    Levoin N, Blondeaua C, Guillaumea C, Grandcolas L, Chretien F, Jouzeau JY, Benoit E, Chapleur Y, Netter P, Lapicque F. Elucidation of the mechanism of inhibition of cyclooxygenases by acyl-coenzyme A and acylglucuronic conjugates of ketoprofen. Biochem Pharmacol. 2004;68(10):1957–69.CrossRefGoogle Scholar
  6. 6.
    Seymour RA, Kelly PJ, Hawkesford JE. The efficacy of ketoprofen and paracetamol (acetaminophen) in postoperative pain after third molar surgery. Br J Clin Pharmacol. 1996;41(6):581–5.CrossRefGoogle Scholar
  7. 7.
    Porażka J, Karbownik A, Murawa D, Spychala A, Firlej M, Grabowski T, Murawa P, Grześkowiak E, Szałek E. The pharmacokinetics of oral ketoprofen in patients after gastric resection. Pharmacol Rep. 2017;69(2):296–9.CrossRefGoogle Scholar
  8. 8.
    Shohin IE, Kulinich JI, Ramenskaya GV, Abrahamsson B, Kopp S, Langguth P, Polli JE, Shah VP, Groot DW, Barends DM, Dressman JB. Biowaiver monographs for immediate-release solid oral dosage forms: ketoprofen. J Pharm Sci. 2012;101(10):3593–603.CrossRefGoogle Scholar
  9. 9.
    Prabhu P, Malli R, Koland M, Vijaynarayana K, D’Souza U, Harish NM, Shastry CS, Charyulu RN. Formulation and evaluation of fast dissolving oral film of levocetirizine di hydrochloride. Int J Pharm Investig. 2011;4(1):337–441.Google Scholar
  10. 10.
    Goel H, Rai P, Rana V, Tiwary AK. Orally disintegrating systems: innovations in formulation and technology. Recent Pat Drug Deliv Formul. 2008;2(3):258–74.CrossRefGoogle Scholar
  11. 11.
    Verma RK, Garg S. Compatibility studies between isosorbide mononitrate and selected excipients used in the development of extended release formulations. J Pharm Biomed Anal. 2004;35(3):449–58.CrossRefGoogle Scholar
  12. 12.
    Araujo AAS, Cides LC, Storpirtis S, Matos JR, Bruns RE. Effects of experimental conditions on the estimation of kinetic parameters of the thermal decomposition of AZT using factorial design. J Therm Anal Calorim. 2005;79(3):697–701.CrossRefGoogle Scholar
  13. 13.
    Murakami FS, Lang KL, Mendes C, Cruz AP, Carvalho Filho MAS, Silva MAS. Physico-chemical solid-state characterization of omeprazole sodium: thermal, spectroscopic and crystallinity studies. J Pharm Biomed Anal. 2009;49(1):72–80.CrossRefGoogle Scholar
  14. 14.
    Tiţa B, Fuliaş A, Bandur G, Marian E, Tiţa D. Compatibility study between ketoprofen and pharmaceutical excipients used in solid dosage forms. J Pharm Biomed Anal. 2011;56(2):221–7.CrossRefGoogle Scholar
  15. 15.
    Ortega A. A simple and precise linear integral method for isoconversional data. Termochimica Acta. 2008;474(1–2):81–6.CrossRefGoogle Scholar
  16. 16.
    Budrugeac P. Differential non-linear isoconversional procedure for evaluating the activation energy of non-isothermal reactions. J Therm Anal Calorim. 2002;68(1):131–9.CrossRefGoogle Scholar
  17. 17.
    Pomerantsev AL, Kutsenova AV, Rodionova OY. Kinetic analysis of non-isothermal solid-state reactions: multi-stage modeling without assumptions in the reaction mechanism. Phys Chem Chem Phys. 2017;19:3606–15.CrossRefGoogle Scholar
  18. 18.
    Ozawa T. A new method of analyzing thermogravimetric data. Bull Chem Soc Jpn. 1965;38(11):1881–6.CrossRefGoogle Scholar
  19. 19.
    Flynn JH, Wall LA. General treatment of the thermogravimetry of polymers. J Res Natl Bur Stand. 1966;70(6):487–523.CrossRefGoogle Scholar
  20. 20.
    Murakami FS, Bernardi LS, Pereira RN, Valente BR, Vasconcelos EC, Carvalho Filho MAS, Silva MAS. Comparative behavior studies of cinnamic acid using isothermal and nonisothermal kinetic methods. Pharm Chem J. 2009;43(12):716–20.CrossRefGoogle Scholar
  21. 21.
    Vueba ML, Pina ME, Veiga F, Sousa JJ, de Carvalho BLAE. Conformational study of ketoprofen by combined DFT calculation and Raman spectroscopy. Int J Pharm. 2006;307(1):56–65.CrossRefGoogle Scholar
  22. 22.
    Fruijtier-Pöllot C. The toxicological mode of action and the safety of synthetic amorphous sílica—a nanostructured material. Toxicology. 2012;294:61–79.CrossRefGoogle Scholar
  23. 23.
    Mura P, Gratteri P, Faucci MT. Compatibility studies of multicomponent tablet formulations. DSC and experimental mixture design. J Therm Anal Calorim. 2002;68(2):541–51.CrossRefGoogle Scholar
  24. 24.
    Veiga A, Oliveira PR, Bernardi LS, Mendes C, Silva MS, Sangoi MS, Janissek PR, Murakami FS. Solid-state compatibility studies of a drug without melting point: the case of omeprazole sodium. J Therm Anal Calorim. 2017.  https://doi.org/10.1007/s10973-017-6756-8.Google Scholar
  25. 25.
    Peres-Filho MJ, Gaeti MPN, Oliveira SR, Marreto RN, Lima EM. Thermoanalytical investigation of olanzapine compatibility with excipients used in solid oral dosage forms. J Therm Anal Calorim. 2011;104(1):255–60.CrossRefGoogle Scholar
  26. 26.
    Mura P, Manderioli 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(1):71–9.CrossRefGoogle Scholar
  27. 27.
    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.CrossRefGoogle Scholar
  28. 28.
    Dragan F, Kacso I, Martin F, Borodi G, Bratu I, Costuleanu M, Sandu IG, Poroch V. Solid state interactions between ketoprofen and excipients in solid dosage forms. Rev Chim. 2016;67(10):2043–8.Google Scholar
  29. 29.
    Bumbrah SG, Sharma RM. Raman spectroscopy—basic principle, instrumentation and selected applications for the characterization of drugs of abuse. Egypt J Forensic Sci. 2016;6(3):209–2015.CrossRefGoogle Scholar
  30. 30.
    Bunaciu AA, Udriştioiu EG, Aboul-Enein HY. X-ray diffraction: instrumentation and applications. Crit Rev Anal Chem. 2015;45(4):289–99.CrossRefGoogle Scholar
  31. 31.
    Yadav PS, Kumar V, Singh PU, Bhat RH, Mazumder B. Physicochemical characterization and in vitro dissolution studies of solid dispersions of ketoprofen with PVP K30 and D-mannitol. Saudi Pharm J. 2013;21(1):77–84.CrossRefGoogle Scholar
  32. 32.
    Dixit M, Parthasarathi KK, Rudra SV. Effect of different crystallization techniques on the dissolution behavior of ketoprofen. Trop J Pharm Res June. 2013;12(3):317–22.Google Scholar
  33. 33.
    Shohin IE, Kulinich JI, Ramenskaya GV, Vasilenko GF. Evaluation of in vitro equivalence for drugs containing BCS class II compound ketoprofen. Dissolution Technol. 2011;19(1):26–9.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2018

Authors and Affiliations

  • Laiane J. Oliveira
    • 1
  • Nayana C. F. Stofella
    • 1
  • Andressa Veiga
    • 1
  • Suélyn Féderle
    • 1
  • Maria da Graça T. Toledo
    • 1
  • Larissa S. Bernardi
    • 2
  • Paulo R. Oliveira
    • 2
  • Marco Aurélio S. Carvalho Filho
    • 3
  • Itamar F. Andreazza
    • 1
  • Fábio S. Murakami
    • 1
  1. 1.Departamento de FarmáciaUniversidade Federal do ParanáCuritibaBrazil
  2. 2.Programa de Pós Graduação em Ciências FarmacêuticasUniversidade Estadual do Centro-Oeste (UNICENTRO)GuarapuavaBrazil
  3. 3.Universidade Positivo – UPCuritibaBrazil

Personalised recommendations