Advertisement

Use of isothermal microcalorimetry in pharmaceutical preformulation studies

  • N. Murti Vemuri
  • Zofia Chrzan
Article

Abstract

Excipient compatibility of a new chemical entity was assessed using an isothermal microcalorimeter. Mixtures of an active pharmaceutical ingredient with a primary amine group and excipients were prepared in a 1:1 ratio and compatibility monitored by exposing to 50, 60 and 70°C in presence of 200 mL of water. The new chemical entity, a primary amine, reacted with reducing sugars such as lactose and resulted in a brown discoloration. This reaction is the Maillard type condensation reaction between amines and reducing sugars. The rate of reaction was dependent on the temperature with rapid degradation at higher temperatures. No other incompatibility was apparent between the primary amine and other excipients

microcalorimetry compatibility excipients browning reaction Maillard reaction primary amine reducing sugars 

References

  1. 1.
    _ A. T. Serajuddin, A. B. Thakur, R. N. Ghosal, M.G. Fakes, S. A. Ranadive, K. R. Morris and S. A. Varia, J. Pharm. Sci., 88 (1998) 696.CrossRefGoogle Scholar
  2. 2.
    A. A. S. Araujo, S. Storpirtis, L. P. Mercuri, F. M. S. Carvalho, M. dos-Santos and J. R. Matos, Int. J. Pharm., 260 (2003) 303.CrossRefGoogle Scholar
  3. 3.
    G. Bruni, L. Amici, V. Berbenni, A. Marini and A. Orlandi, J. Therm. Anal. Cal., 68 (2002) 561.CrossRefGoogle Scholar
  4. 4.
    A. Marini, V. Berbenni, S. Moioli, G. Bruni, P. Cofrancesco, C. Margheritis and M. Villa, J. Therm. Anal. Cal., 73 (2003) 529.CrossRefGoogle Scholar
  5. 5.
    X. Tan, N. Meltzer and S. Lindenbaum, Pharm. Res., 9 (1992) 1203.CrossRefGoogle Scholar
  6. 6.
    E. A. Schmitt, K. Peck, Y. Sun and J. M. Geoffroy, Thermochim. Acta, 380 (2001) 175.CrossRefGoogle Scholar
  7. 7.
    L. Wadsö, A. L. Smith, H. Shirazi, S. R. Mulligan and T. Hafelich, J. Chem. Educ., 78 (2001) 1080.CrossRefGoogle Scholar
  8. 8.
    R. D. Vickery and M. B. Maurin, Utility of microcalorimetry in the characterization of the browning reaction. Journal of Pharmaceutical and Biomedical Analysis, 20 (1999) 385.CrossRefGoogle Scholar
  9. 9.
    L. D. Hansen, E. A. Lewis, D. J. Eatough, R. G. Bergstrom and D. DeGraft-Johnson, Pharm. Res., 6 (1989) 20.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publisher/Akadémiai Kiadó 2004

Authors and Affiliations

  • N. Murti Vemuri
    • 1
  • Zofia Chrzan
    • 1
  1. 1.Aventis Pharmaceuticals Route 202/206 SBridgewaterUSA

Personalised recommendations