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      Stability of apomorphine in solutions containing selected antioxidant agents

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          Abstract

          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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          Removal of dissolved oxygen from water: A comparison of four common techniques.

          Four common techniques for the removal of dissolved oxygen from water have been examined: boiling at 1 atm, boiling under reduced pressure, purging with N(2) and sonication under reduced pressure. After treatment, the residual oxygen in solution was analysed by the Winkler method. Nitrogen purging for 20-40 min at flow rate of 25 mL/s was found to be the most effective oxygen removal method. Boiling at 1 atm was found to be the least effective. None of the techniques evaluated here lead to complete removal of oxygen. The concentration of residual dissolved oxygen after purging for 20-40 minutes with nitrogen is 0.2-0.4 ppm.
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            Apomorphine in dopaminergic therapy.

             J Subramony (2006)
            Apomorphine is a potent molecule for the treatment of Parkinson's disease (PD). It can be obtained in both the R and S forms, and it is the former that is the therapeutically active form. Due to its structural similarity with 3,4-dihydroxyphenethylamine, dopamine, apomorphine can function as an agonist in the treatment of PD as it can stimulate both the D1 and D2 receptors of the striatum. The clinical efficacy of apomorphine is similar to that of 3,4-dihydroxyphenylalanine, levodopa (L-dopa), the cornerstone drug in dopaminergic therapy. (R)-Apomorphine is efficacious for one of the most challenging aspects in the management of PD, namely, managing the unpredictable "on-off" period as a rescue medication after oral administration of a therapeutic drug such as L-dopa. The effectiveness is due to its rapid control of the wearing-off period of the orally administered medicine. This short review will trace the progress of apomorphine use starting with its initial discovery and the first indications for which it was used, discovery of its "cure" for PD, and the studies that led to demonstrating its therapeutic efficacy. The key structural features of apomorphine responsible for its activity are illustrated along with major issues of chemical stability. From a drug delivery point of view, the current form of administration of apomorphine and some of the potential alternate methods of delivery are reviewed.
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              New insights into the oxidation pathways of apomorphine

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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                03 October 2016
                : 10
                : 3253-3265
                Affiliations
                School of Pharmacy, Faculty of Health Sciences, Curtin University, Bentley, WA, Australia
                Author notes
                Correspondence: Zen Yang Ang, Pharmacy Department, Oncology and Radiotherapy Institution, General Hospital of Kuala Lumpur, Kuala Lumpur, Malaysia, Tel +60 13 488 9045, Email angzenyang@ 123456gmail.com
                Article
                dddt-10-3253
                10.2147/DDDT.S116848
                5055109
                © 2016 Ang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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