AAPS PharmSci

, Volume 3, Issue 1, pp 18–25 | Cite as

Physical chemical stability of warfarin sodium

  • Danchen Gao
  • Michael B. Maurin


Crystalline warfarin sodium is an isopropanol clathrate containing 8.3% isopropyl alcohol (IPA) and 0.57% water upon receipt. The hygroscopicity and impact of moisture on IPA status as well as on the stability of the clathrate was studied at different relative humidities. The IPA loss and water uptake were simultaneous but they did not exchange at 1:1 molar ratio. At 58% relative humidity (RH) or below, the exchange process was insignificant. At 68% RH or above, the clathrate tended to lose IPA while absorbing water and reverting to the amorphous state. The rate of IPA loss and moisture uptake was a function of RH. The thermal stability of the crystalline warfarin sodium was also examined. Physical change occurred after isothermal storage for 24 hours at 80°C and 11 hours at 120°C. The rate of IPA loss was temperature dependent.


warfarin sodium isopropyl alcohol clathrate amorphous crystallinity physical stability thermal stability 


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  1. 1.
    Schroeder CH, Link KP, inventors, Wisconsin Alumni Research Foundation. Warfarin sodium, US patent 3077 481. February 12, 1963.Google Scholar
  2. 2.
    US Pharmacopoeia. The National Formulary, USP 24/NF19, United States Pharmacopocia Convention: Rockville. Md. 2000.Google Scholar
  3. 3.
    Physicians Desk Reference®; 2000:969–974. Medical Economics Company, Inc. Montvale, NJ, 54th edition.Google Scholar
  4. 4.
    Hiskey CF, Melnitchenko V. Clathrates of sodium warfarin. J Pharm Sci. 1965;54:1298–1302.PubMedCrossRefGoogle Scholar
  5. 5.
    Gao D, Rytting JH. Use of solution calorimetry to determine the extent of crystallinity of drugs and excipients. Int J Pharm. 1997;151:183–192.CrossRefGoogle Scholar
  6. 6.
    Nyqvist H. Saturated salt solutions for maintaining specified relative humidities. J Pharm Tech Prod Mfr. 1983;4:47–48.Google Scholar
  7. 7.
    Rabel SR, Jona JA, Maurin MB. Applications of modulated differential scanning calorimetry in preformulation studies. J Pharm Biomed Anal. 1999;21:339–345.PubMedCrossRefGoogle Scholar
  8. 8.
    Umprayn K, Mendes RW. Hygroscopicity and moisture absorption kinetics of pharmaceutical solids a review. Drug Dev Ind Pharm. 1987;13:653–693.CrossRefGoogle Scholar
  9. 9.
    Franks F, Finch CA, eds. Water solubility and sensitivity-hydration effects, chemistry and technology of water soluble polymers. New York, NY: Plenum Press, 1981.Google Scholar
  10. 10.
    Hancock BC, Zografi G. The use of solution theories for predicting water vapor absorption by amorphous pharmaceutical solids a test of the Flory-Huggins and Vrental models. Pharm Res. 1993;10:1262–1267.PubMedCrossRefGoogle Scholar
  11. 11.
    Seymour RB, Carraher CE Jr. Polymer Chemistry, An Introduction. 3rd ed. New York: Marcel Dekker, Inc.: 1992.Google Scholar
  12. 12.
    Hancock BC, Zografi G. The relationship between the glass transition temperature and the water content of amorphous pharmaceutical solids. Pharm Res. 1994;11:471–477.PubMedCrossRefGoogle Scholar
  13. 13.
    Mandelcom L. Clathrates Chem Rev. 1959;59:827–839.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2001

Authors and Affiliations

  1. 1.Pharmaceutical Sciences, PharmaciaSkokie
  2. 2.Pharmacy R&DDuPont Pharmaceuticals CompanyWilmington

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