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Effect of self-association on rate of penicillin G degradation in concentrated aqueous solutions

J T Ong, H B Kostenbauder

    Journal of Pharmaceutical Sciences
    |August 1, 1975
    PubMed

    Insights

    Penicillin G potassium micellar solutions show increased stability compared to nonmicellar forms. This study investigated degradation rates, finding micellar penicillin G to be 2.5 times more stable at its optimal pH.

    Area of Science:

    • Pharmaceutical Sciences
    • Physical Chemistry

    Background:

    • Penicillin G potassium is frequently prepared at high concentrations (500,000 units/ml) for storage.
    • Understanding degradation kinetics is crucial for maintaining drug efficacy.
    • Micellar solutions can alter drug stability and degradation pathways.

    Purpose of the Study:

    • To investigate the degradation rate of penicillin G potassium in micellar solutions.
    • To compare the stability of micellar versus nonmicellar penicillin G solutions.
    • To determine the effect of micellar formation on penicillin G degradation kinetics across a pH range.

    Main Methods:

    • Comparative kinetic analysis of penicillin G potassium degradation.
    • Investigation of micellar and nonmicellar solutions at 25°C and ionic strength of 1.1 M.
    • Determination of pH-rate profiles between pH 5.0 and 9.5.

    Main Results:

    • Micellar solutions exhibited a twofold increase in H+-catalyzed degradation but a two- to threefold decrease in water- and OH−-catalyzed hydrolysis.
    • The pH of minimum degradation shifted to 7.0 for micellar solutions, compared to 6.5 for nonmicellar solutions.
    • At their respective pH minima, micellar penicillin G demonstrated 2.5 times greater stability than nonmicellar solutions.

    Conclusions:

    • Micellar formulation of penicillin G potassium significantly alters its degradation profile.
    • Micellar solutions offer enhanced stability for penicillin G potassium, particularly at neutral pH.
    • Optimized storage conditions for micellar penicillin G potassium can be achieved at a slightly higher pH compared to nonmicellar forms.

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