Pharmaceutical Research

, Volume 22, Issue 2, pp 310–317

Use of 2,2′-Azobis(2-Amidinopropane) Dihydrochloride as a Reagent Tool for Evaluation of Oxidative Stability of Drugs

  • Seema Betigeri
  • Ajit Thakur
  • Krishnaswamy Raghavan
Research Papers

DOI: 10.1007/s11095-004-1199-x

Cite this article as:
Betigeri, S., Thakur, A. & Raghavan, K. Pharm Res (2005) 22: 310. doi:10.1007/s11095-004-1199-x

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Purpose.

To study the oxidative degradation of drugs using a hydrophilic free radical initiator, 2,2′-Azobis(-amidinopropane) dihydrochloride (AAPH).

Methods.

AAPH was used as the free radical initiator to study oxidation of three model compounds (A, B, and C), which represent different oxidizable moieties. In the solution model, the drugs and AAPH were dissolved in a mixture of acetonitrile and aqueous buffer and incubated at elevated temperatures to evaluate oxidative degradation. The effects of pH and drug-AAPH ratio on the kinetics of the reaction were evaluated for compound A. Commonly used antioxidants were also evaluated by addition to solutions of drug and AAPH. In the solid-state model, blends of drug with microcrystalline cellulose were treated with AAPH and placed at elevated temperature and humidity to evaluate solid state oxidation.

Results.

Use of AAPH resulted in selective oxidation of the model drugs by a free radical initiated process. The scope of the technique was further investigated in detail using compound A. The rate of oxidation of compound A varied directly with the concentration of AAPH. The pseudo first-order rate constants for the oxidative degradation were calculated from the kinetic data. The antioxidants were rank-ordered based on their quenching activity on the rates of AAPH initiated oxidation for compound A. The concept was extended to oxidation in solid state.

Conclusions.

The proposed AAPH model is useful in assessing oxidative stability of drug candidates in development.

Key words:

antioxidant 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) oxidation free radicals 

Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • Seema Betigeri
    • 1
  • Ajit Thakur
    • 1
  • Krishnaswamy Raghavan
    • 1
  1. 1.Biopharmaceutics R&D, Pharmaceutical Research InstituteBristol-Myers Squibb Co.New BrunswickUSA

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