Thermal behavior of verapamil hydrochloride and its association with excipients

  • Ronaldo S. Nunes
  • Felipe S. Semaan
  • Alan T. Riga
  • Éder T. G. Cavalheiro


The thermal properties of verapamil hydrochloride (VRP) and its physical association as binary mixtures with some common excipients were evaluated. Thermogravimetry (TG) was used to determine the thermal mass loss, as well as to study the kinetics of VRP thermal decomposition, using the Flynn-Wall-Ozawa model. Based on their frequent use in pharmacy, five different excipients (microcrystalline cellulose, magnesium stearate, hydroxypropyl methylcellulose, polyvinylpyrrolidone and talc) were blended with VRP. Samples were prepared by mixing the analyte and excipients in a proportion of 1:1 (m/m). DSC curves for pure VRP presented an endothermic event at 143 ± 2 °C (ΔHmelt = 132 ± 4 J g−1), which corresponds to the melting (literature Tm = 143.7 °C, ΔHmelt = 130.6 J g−1). Comparisons among the observed results for each compound and their binary physical mixtures presented no relevant changes. This suggests no interaction between the drug and excipient.


Excipient interaction Thermal analysis Verapamil hydrochloride 


  1. 1.
    Balestrieri F, Magri AD, Magri AL, Marini D, Sacchini A. Application of differential scanning calorimetry to the study of drug-excipient compatibility. Thermochim Acta. 1996;285:337–45.CrossRefGoogle Scholar
  2. 2.
    Cotton ML, Wu DW, Vadas EB. Drug excipient interaction study of enalapril maleate using thermal-analysis and scanning electron-microscopy. Int J Pharm. 1987;40:129–42.CrossRefGoogle Scholar
  3. 3.
    Li Wan Po A, Mroso PV. Drug–drug incompatibility in the solid state: kinetic interpretation, modelling and prediction. Int J Pharm. 1984;18:287–98.CrossRefGoogle Scholar
  4. 4.
    Mroso PV, Li Wan Po A, Irwin WJ. Solid-state stability of aspirin in the presence of excipients—kinetic interpretation, modeling, and prediction. J Pharm Sci. 1982;71:1096–101.CrossRefGoogle Scholar
  5. 5.
    Botha SA, Lotter AP. Compatibility study between atenolol and tablet excipients using differential scanning calorimetry. Drug Dev Ind Pharm. 1990;16:1945–54.CrossRefGoogle Scholar
  6. 6.
    Vantonder EC, Lotter AP, Botha SA. Compatibility study between doxylamine succinate with other drugs and excipients using differential scanning calorimetry. Drug Dev Ind Pharm. 1990;16:2125–33.CrossRefGoogle Scholar
  7. 7.
    Donauer N, Lönbenberg R. A mini review of scientific and pharmacopeial requirements for the disintegration test. Int J Pharm. 2007;345:2–8.CrossRefGoogle Scholar
  8. 8.
    Schomerus M, Spiegelhaider B, Stieren B, Eichelbaum M. Physiological disposition of verapamil in man. Cardiovasc Res. 1976;10:605–12.CrossRefGoogle Scholar
  9. 9.
    Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–66.CrossRefGoogle Scholar
  10. 10.
    Flynn JH, Wall LA. General treatment of thermogravimetry of polymers. J Res Natl Bur Stand A: Phys Chem. 1966;70:487–523.Google Scholar
  11. 11.
    Vyazovkin S, Wight CA. Isothermal and non-isothermal kinetics of thermally stimulated reactions of solids. Int Rev Phys Chem. 1998;17:407–33.CrossRefGoogle Scholar
  12. 12.
    Flynn JH, Wall LA. A quick direct method for determination of activation energy from thermogravimetric data. J Polym Sci B: Polym Lett. 1966;4:323–8.CrossRefGoogle Scholar
  13. 13.
    Doyle CD. Kinetic analysis of thermogravimetric data. J Appl Polym Sci. 1961;5:285–92.CrossRefGoogle Scholar
  14. 14.
    Rustichelli C, Gamberini MC, Ferioli V, Gamberini G. Properties of the racemic species of verapamil hydrochloride and gallopamil hydrochloride. Int J Pharm. 1999;178:111–20.CrossRefGoogle Scholar
  15. 15.
    Abbas D, Kaloustian J, Orneto C, Piccerelle P, Portugal H, Nicolay A. DSC and physico-chemical properties of a substituted pyridoquinoline and its interaction study with excipients. J Therm Anal Calorim. 2008;93:353–60.CrossRefGoogle Scholar
  16. 16.
    American standard test method for oxidation onset temperature of hydrocarbons by differential scanning calorimetry, vol. 14.02. PA: ASTM International E2009-08; 2008.Google Scholar
  17. 17.
    Guinesi LS, Ribeiro CA, Crespi MS, Santos AF, Capela MV. Titanium(IV)–EDTA complex. J Therm Anal Calorim. 2006;85:301–7.CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2009

Authors and Affiliations

  • Ronaldo S. Nunes
    • 1
  • Felipe S. Semaan
    • 1
  • Alan T. Riga
    • 2
  • Éder T. G. Cavalheiro
    • 1
  1. 1.Departamento de Química e Física Molecular, Instituto de Química de São CarlosUSPSao CarlosBrazil
  2. 2.Pharmacy Practice Department, College of PharmacyThe University of ToledoToledoUSA

Personalised recommendations