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The effect of sodium metabisulfite concentration upon the stability of epinephrine in a Lidocaine HC1 with Epinephrine solution was evaluated using an elevated temperature (60°C) screen for up to 35 days. Long term room temperature data (23'C) was collected and evaluated for up to forty months and substantiated the results observed in the accelerated studies. Enhancement of the epinephrine chemical stability was predicated upon a tenfold reduction in the metabisulfite level from 0.05% to 0.005% plus the inclusion of a specific chelating agent, disodium edetate, into the formula. Protection from light is of optimum importance since more rapid photolytic degradation occurred in the experimental formula than 1549 Copyright 0 1992 by Marcel Dekker, Inc. Drug Dev Ind Pharm Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only. 1550 GRUBSTEIN AND MILAN0 in the control. In two distinct packages, 20 ml glass vials and 1.8 ml glass cartridges, the epinephrine stability was found to be significantly improved (p < 0.05) compared to a control, suggesting the possibility of increased expiration dating. I " In aqueous solutions epinephrine decomposes by several pathways which can occur consecutively and in parallel. The principal degradation route is oxidative and is accelerated by the presence of oxygen, heavy metals, ultraviolet light, and increased pH 1-5. to prolong the shelf-life of oxygen-sensitive products. These agents may be preferentially degraded due to their higher oxidation potential or act as free radical acceptors, chain inhibitors, or as sequestering agents 6 . solutions containing epinephrine, sulfite salts have demonstrated the unique ability to reduce the rate of oxidative degradation and retard the ensuant discoloration. Levels from 0.025% to 0.1% have been included in most marketed products containing epinephrine. Direct and indirect agents have been used In local anesthetic Drug Dev Ind Pharm Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15 For personal use only. 9 Drug Dev Ind Pharm Downloaded from informahealthcare.com by Nyu Medical Center on 05/29/15For personal use only.

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