Stability of apomorphine in solutions containing selected antioxidant agents

Apomorphine in solution undergoes rapid autoxidation, producing greenish colored solutions, making it difficult to formulate as a stable pharmaceutical solution. To identify the optimum antioxidant agent/combination for apomorphine solution, a high performance liquid chromatography assay was used to...

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Main Authors: Ang, Zen Yang, Boddy, Michael, Liu, Yandi, Sunderland, Bruce
Format: Journal Article
Published: Dove Medical Press Ltd. 2016
Online Access:http://hdl.handle.net/20.500.11937/58960
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author Ang, Zen Yang
Boddy, Michael
Liu, Yandi
Sunderland, Bruce
author_facet Ang, Zen Yang
Boddy, Michael
Liu, Yandi
Sunderland, Bruce
author_sort Ang, Zen Yang
building Curtin Institutional Repository
collection Online Access
description Apomorphine in solution undergoes rapid autoxidation, producing greenish colored solutions, making it difficult to formulate as a stable pharmaceutical solution. To identify the optimum antioxidant agent/combination for apomorphine solution, a high performance liquid chromatography assay was used to study the stability of 50 µg/mL apomorphine HCI in 0.1% L-ascorbic acid (AA), 0.1% sodium metabisulfite (SMB), 0.1% EDTA, and in selected combinations at 25°C, 32°C, and 37°C over a period of 14 days. The stability of apomorphine HCl (10 mg/mL) in 0.1% AA solution and in 0.1% EDTA solution at 25°C and 37°C was also evaluated. Apomorphine HCI solution (50 µg/mL) in 0.1% AA plus 0.1% SMB solution retained 99.7% (at 25°C) and 95.9% (at 37°C) of the initial concentration, as 0.1% AA plus SMB solution minimized the reactive oxygen content in solution which, in turn, reduced the oxidation rate of apomorphine HCl, and there was no green coloration perceptible. Conversely, apomorphine HCl solution (50 µg/mL) in 0.1% SMB solution was unstable as only 0.53% (at 25°C) and 0.06% (at 37°C) of the initial concentration was retained after 14 days. All 10 mg/mL apomorphine HCl samples were stable in both studies. The initial concentration of apomorphine HCl solution markedly affected its rate of oxidation and discoloration. The addition of 0.1% AA to a current formulation of apomorphine HCl injection (Apomine(®)), which contains SMB as an antioxidant, was recommended as providing the most stable solution.
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spelling curtin-20.500.11937-589602018-01-11T04:08:04Z Stability of apomorphine in solutions containing selected antioxidant agents Ang, Zen Yang Boddy, Michael Liu, Yandi Sunderland, Bruce Apomorphine in solution undergoes rapid autoxidation, producing greenish colored solutions, making it difficult to formulate as a stable pharmaceutical solution. To identify the optimum antioxidant agent/combination for apomorphine solution, a high performance liquid chromatography assay was used to study the stability of 50 µg/mL apomorphine HCI in 0.1% L-ascorbic acid (AA), 0.1% sodium metabisulfite (SMB), 0.1% EDTA, and in selected combinations at 25°C, 32°C, and 37°C over a period of 14 days. The stability of apomorphine HCl (10 mg/mL) in 0.1% AA solution and in 0.1% EDTA solution at 25°C and 37°C was also evaluated. Apomorphine HCI solution (50 µg/mL) in 0.1% AA plus 0.1% SMB solution retained 99.7% (at 25°C) and 95.9% (at 37°C) of the initial concentration, as 0.1% AA plus SMB solution minimized the reactive oxygen content in solution which, in turn, reduced the oxidation rate of apomorphine HCl, and there was no green coloration perceptible. Conversely, apomorphine HCl solution (50 µg/mL) in 0.1% SMB solution was unstable as only 0.53% (at 25°C) and 0.06% (at 37°C) of the initial concentration was retained after 14 days. All 10 mg/mL apomorphine HCl samples were stable in both studies. The initial concentration of apomorphine HCl solution markedly affected its rate of oxidation and discoloration. The addition of 0.1% AA to a current formulation of apomorphine HCl injection (Apomine(®)), which contains SMB as an antioxidant, was recommended as providing the most stable solution. 2016 Journal Article http://hdl.handle.net/20.500.11937/58960 10.2147/DDDT.S116848 https://creativecommons.org/licenses/by-nc/3.0/ Dove Medical Press Ltd. fulltext
spellingShingle Ang, Zen Yang
Boddy, Michael
Liu, Yandi
Sunderland, Bruce
Stability of apomorphine in solutions containing selected antioxidant agents
title Stability of apomorphine in solutions containing selected antioxidant agents
title_full Stability of apomorphine in solutions containing selected antioxidant agents
title_fullStr Stability of apomorphine in solutions containing selected antioxidant agents
title_full_unstemmed Stability of apomorphine in solutions containing selected antioxidant agents
title_short Stability of apomorphine in solutions containing selected antioxidant agents
title_sort stability of apomorphine in solutions containing selected antioxidant agents
url http://hdl.handle.net/20.500.11937/58960