Drug development and industrial pharmacy · 2026
Degradation kinetics of apomorphine hydrochloride in buffered formulations and the effect of antioxidants.
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Al-Ghananeem Abeer M, Baltzley Sarah, Malkawi Azzam A, Boddu Sai Hs
Аннотация
INTRODUCTION: Apomorphine (APO) is inherently unstable in aqueous solutions, as it forms auto-oxidation products. The study investigates the degradation kinetics of APO as the function of pH and evaluates the stabilizing effects of antioxidants (i.e. ascorbic acid (AA) and sodium metabisulfite (SMB)) on APO solution formulations.
SIGNIFICANCE: To understand combined impact of pH-adjustment, buffer concentrations and antioxidant addition on the degradation kinetics of APO.
METHODS: The degradation kinetics of APO in solutions and the antioxidant effect were investigated with a reversed-phase HPLC system. The influences of pH value on degradation of APO were studied in aqueous solutions. Stability studies were performed under a nitrogen blanket and protected from light to minimize oxidative and light-induced degradation and allow aqueous degradation in order to establish the pH-rate profile of APO in aqueous media.
RESULTS: APO in aqueous solution showed rapid degradation with pseudo-first-order kinetics at 25 °C. The log ko-pH profile indicated that the optimal stability range for APO was at acidic pH values of 2.4-2.6. Degradation rate constants were determined for reactions run over pH values range of 2.0-8.0. The lowest molar buffer concentration used at 0.01 M, resulted in a more stable APO formulation. AA used at 1% as an antioxidant in APO formulation appeared to be superior against APO degradation with 97.4% of APO remaining, while 50% SMB formulation had the most APO degradation with 94.25% APO remaining after 6 months.
CONCLUSION: The APO aqueous formulation at pH 2.4-2.6 with 1% AA is recommended to maximize stability and clinical tolerability.
SIGNIFICANCE: To understand combined impact of pH-adjustment, buffer concentrations and antioxidant addition on the degradation kinetics of APO.
METHODS: The degradation kinetics of APO in solutions and the antioxidant effect were investigated with a reversed-phase HPLC system. The influences of pH value on degradation of APO were studied in aqueous solutions. Stability studies were performed under a nitrogen blanket and protected from light to minimize oxidative and light-induced degradation and allow aqueous degradation in order to establish the pH-rate profile of APO in aqueous media.
RESULTS: APO in aqueous solution showed rapid degradation with pseudo-first-order kinetics at 25 °C. The log ko-pH profile indicated that the optimal stability range for APO was at acidic pH values of 2.4-2.6. Degradation rate constants were determined for reactions run over pH values range of 2.0-8.0. The lowest molar buffer concentration used at 0.01 M, resulted in a more stable APO formulation. AA used at 1% as an antioxidant in APO formulation appeared to be superior against APO degradation with 97.4% of APO remaining, while 50% SMB formulation had the most APO degradation with 94.25% APO remaining after 6 months.
CONCLUSION: The APO aqueous formulation at pH 2.4-2.6 with 1% AA is recommended to maximize stability and clinical tolerability.