Journal of Thermal Analysis and Calorimetry

, Volume 134, Issue 1, pp 721–730 | Cite as

The kinetic study of the thermally induced degradation and an evaluation of the drug–excipient interactions performed for a new-generation bisphosphonate—risedronate

  • Gabriela Vlase
  • Paul Albu
  • Sorin Cristian Doca
  • Madalina Mateescu
  • Titus Vlase


Sodium risedronate (Rise) is a third generation of bisphosphonates, compounds active in suppressing the bone resorption and therefore used in orthopedy, dentistry and bone cancer treatment. The stability of Rise as bioactive compound was studied by thermoanalysis (TA) and kinetic analysis under non-isothermal conditions, as well as by FTIR spectroscopy of samples treated at different temperatures. The data were compared with these obtained for similar compounds (sodium alendronate and zoledronic acid) and reveal a low stability: The decomposition begins under 100 °C, and the activation energy is relatively small. The possibilities of increasing the thermal stability were studied using binary mixture (1:1) in mass parts of Rise with talc, silica, mannitol, starch, microcrystalline cellulose and magnesium stearate. By both methods, TA and FTIR interaction between Rise and mannitol was detected. Regarding the kinetic analysis, the nonparametric kinetic methods reveal its advantages by an objective and complete kinetic description of Rise thermal decomposition.


Risedronate–excipients mixture Thermally induced interactions Non-isothermal kinetics 


  1. 1.
    Mathoo JMR, Cranney A, Papaioannou A, Adachi JD. Rational use of oral bisphosphonates for the treatment of osteoporosis. Curr Osteoporos Rep. 2004;2:17–23.CrossRefGoogle Scholar
  2. 2.
    Hongo M, Miyakoshi N, Kasukawa Y, Ishikawa Y. Shimada, prevalence of sarcopenia in Japanese women with osteopenia and osteoporosis. J Bone Miner Metab. 2015;33:432–9.CrossRefGoogle Scholar
  3. 3.
    Molvik H, Khan W. Bisphosphonates and their influence on fracture healing: a systematic review. Osteoporos Int. 2015;26:1251–60.CrossRefGoogle Scholar
  4. 4.
    Rodan GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest. 1996;97:2692–6.CrossRefGoogle Scholar
  5. 5.
    Russell RGG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008;19(6):733–59.CrossRefGoogle Scholar
  6. 6.
    Nancollas GH, Tang R, Phipps RJ, Henneman Z, Gulde S, Wu W, Mangood A, Russell RG, Ebetino FH. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone. 2006;38(5):617–27.CrossRefGoogle Scholar
  7. 7.
    Torstrick FB, Guldberg RE. Local strategies to prevent and treat osteoporosis. Curr Osteoporos Rep. 2014;12:33–40.CrossRefGoogle Scholar
  8. 8.
    Gupta MS, Nicoll SB. Functional nucleus pulposus-like matrix assembly by human mesenchymal stromal cells is directed by macromer concentration in photocrosslinked carboxymethylcellulose hydrogels. Cell Tissue Res. 2014;358:527–39.CrossRefGoogle Scholar
  9. 9.
    Luckman SP, Hughes DE, Coxon FP, Graham R, Russell G, Roggers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998;13(4):581–9.CrossRefGoogle Scholar
  10. 10.
    Mendonça LT, Pinheiro MM, Szejnfeld VL, Heldan C, Castro DM. Bone mass outcomes in patients with osteoporosis treated with risedronate after alendronate failure: a 12-month follow-up study. J Clin Densitom. 2017;20(1):44–9.CrossRefGoogle Scholar
  11. 11.
    Malavasi M, Ricardo L, Marcelo BB, Lucas NT, Peruzzo DC, Joly JC, Martinez EF, Napimoga MH. Effects of risedronate on osteoblastic cell cultures. Arch Oral Biol. 2016;68:43–7.CrossRefGoogle Scholar
  12. 12.
    Pasqualone M, Héctor AA, Cortizo MS. Risedronate transdermal delivery system based on a fumaric copolymer for therapy of osteoporosis. Mater Sci Eng C. 2017;76:652–8.CrossRefGoogle Scholar
  13. 13.
    Bedoya DA, Vasti C, Rojas R, Giacomelli CE. Applied clay science risedronate functionalized layered double hydroxides nanoparticles with bone targeting capabilities. Appl Clay Sci. 2017;141:257–64.CrossRefGoogle Scholar
  14. 14.
    Albu P, Doca SC, Anghel A, Vlase G, Vlase T. Thermal behavior of sodium alendronate. J Therm Anal Calorim. 2017;127(1):571–6.CrossRefGoogle Scholar
  15. 15.
    Doca SC, Albu P, Ceban I, Anghel A, Vlase G, Vlase T. Sodium alendronate used in bone treatment. J Therm Anal Calorim. 2016;126(1):189–94.CrossRefGoogle Scholar
  16. 16.
    Paul A, Budiul M, Mateescu M, Chiriac V, Vlase G, Vlase T. Studies regarding the induced thermal degradation, kinetic analysis and possible interactions with various excipients of an osseointegration agent—zoledronic acid. J Therm Anal Calorim. 2017;130(1):403–11.CrossRefGoogle Scholar
  17. 17.
    Kumar D, Disha C, Vasireddi R, Razdan R, Mahapatra DR. Risedronate/zinc- hydroxyapatite based nanomedicine for osteoporosis. Mater Sci Eng C. 2016;63:78–87.CrossRefGoogle Scholar
  18. 18.
    Rawat P, Ahmad I, Thomas SC, Pandey S, Vohora D, Gupta S, Ahmad FJ, Talegaonkar S. Revisiting bone targeting potential of novel hydroxyapatite based surface modified PLGA nanoparticles of risedronate: pharmacokinetic and biochemical assessment. Int J Pharma. 2016;506:253–61.CrossRefGoogle Scholar
  19. 19.
    Friedman HL. Kinetics of thermal degradation of char-foaming plastics from thermogravimetry: application to a phenolic resin. J Polym Sci. 1965;6C:183–95.Google Scholar
  20. 20.
    Flynn JH, Wall LA. A quick, direct method for the determination of activation energy from thermogravimetric data. Polym Lett. 1966;4:323–8.CrossRefGoogle Scholar
  21. 21.
    Ozawa T. A new method of analyzing thermogravimetric data. Bull Chem Soc Jpn. 1965;38:1881–6.CrossRefGoogle Scholar
  22. 22.
    Serra R, Nomen R, Sempere J. The non-parametric kinetics. A new method for the kinetic study of thermoanalytical data. J Therm Anal Calorim. 1998;52:933–43.CrossRefGoogle Scholar
  23. 23.
    Serra R, Sempere J, Nomen R. A new method for the kinetic study of thermoanalytical data: the non-parametric kinetics method. Thermochim Acta. 1998;316:37–45.CrossRefGoogle Scholar
  24. 24.
    Vlase T, Vlase G, Doca N, Bolcu C. Processing of non-isothermal TG data. Comparative kinetic analysis with NPK method. J Therm Anal Calorim. 2005;80:59–64.CrossRefGoogle Scholar
  25. 25.
    Vlase T, Vlase G, Doca N, Ilia G, Fulias A. Coupled thermogravimetric-IR techniques and kinetic analysis by non-isothermal decomposition of Cd2 + and Co2 + vinyl-phosphonates. J Therm Anal Calorim. 2009;97:467–72.CrossRefGoogle Scholar
  26. 26.
    Brown ME, Maciejewski M, Vyazovkin S, Nomen R, Sempere J, Burnham A, et al. Computational aspects of kinetic analysis: part A: the ICTAC kinetics project-data, methods and results. Thermochim Acta. 2000;355:125–43.CrossRefGoogle Scholar
  27. 27.
    Fuliaş A, Ledeţi I, Vlase G, Vlase T, Şoica C, Dehelean C, Oprean C, Bojin F, Şuta LM, Bercean V, Avram Ş. Thermal degradation, kinetic analysis, and apoptosis induction in human melanoma for oleanolic and ursolic acids. J Therm Anal Calorim. 2016;125:759–68.CrossRefGoogle Scholar
  28. 28.
    Vlase G, Bolcu C, Modra D, Budiul MM, Ledeţi I, Albu P, Vlase T. Thermal behavior of phthalic anhydride-based polyesters. J Therm Anal Calorim. 2016;126:287–92.CrossRefGoogle Scholar
  29. 29.
    Ceban I, Blajovan R, Vlase G, Albu P, Koppandi O, Vlase T. Thermoanalytical measurements conducted on repaglinide to estimate the kinetic triplet followed by compatibility studies between the antidiabetic agent and various excipients. J Therm Anal Calorim. 2016;126:195–204.CrossRefGoogle Scholar
  30. 30.
    Patrutescu C, Vlase G, Turcus V, Ardelean D, Vlase T, Albu P. TG/DTG/DTA data used for determining the kinetic parameters of the thermal degradation process of an immunosuppressive agent: mycophenolate mofetil. J Therm Anal Calorim. 2015;121(3):983–8.CrossRefGoogle Scholar
  31. 31.
    Wall ME. Singular value decomposition and principal component analysis. In: Berrar DP, Dubitzky W, Granzow M, editors. A practical approach to microarray data analysis, vol. 9. MA: Kluwer-Norwel. 2003. p. 91–109.Google Scholar
  32. 32.
    Śestak J, Berggren G. Study of the kinetics of the mechanism of solid-state reactions at increasing temperatures. Thermochim Acta. 1971;3:1–12.CrossRefGoogle Scholar
  33. 33.
    Stuart B. Infrared spectroscopy: fundamentals and applications. Hoboken: Wiley; 2004.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2018

Authors and Affiliations

  1. 1.Research Center for Thermal Analysis in Environmental ProblemsWest University of TimisoaraTimisoaraRomania
  2. 2.Faculty of MedicineUniversity of Medicine and Pharmacy “Victor Babes”TimisoaraRomania

Personalised recommendations