Epinephrine Compositions And Containers

What is this patent about?

’837 is related to the field of pharmaceutical formulations, specifically addressing the challenge of creating a stable, ready-to-administer epinephrine solution. Epinephrine, a crucial medication for treating severe allergic reactions and other emergencies, is known to degrade rapidly in aqueous solutions, especially when diluted. Existing solutions often require dilution prior to use, increasing the risk of dosage errors and contamination, and have a short shelf life, necessitating frequent preparation and disposal.

The underlying idea behind ’837 is to formulate a low-concentration epinephrine solution that remains stable over an extended period without the need for antioxidants, which can themselves cause allergic reactions. This is achieved by carefully controlling several factors: maintaining a mildly acidic pH, using a metal ion chelator to prevent degradation catalyzed by metal ions, minimizing dissolved oxygen, and packaging the solution in a way that protects it from light and oxygen exposure. The low concentration allows for direct administration without prior dilution, reducing the risk of errors.

The claims of ’837 focus on a sterile, storage-stable, ready-to-inject epinephrine composition. The key elements include an aqueous carrier, epinephrine at a concentration of 0.07 mg/ml or less with a high percentage of the R-isomer, a pH between 3.0 and 4.7, a tonicity agent, and a metal ion chelator (bicarboxylic, tricarboxylic, or aminopolycarboxylic acid) at a concentration between 1 and 50 μg/ml. The composition must maintain a total impurities concentration of 0.3% or less after one month of storage at 25°C. A related claim covers a method of producing such a composition, including autoclaving for sterilization.

In practice, the invention involves carefully preparing an aqueous solution of epinephrine with a low concentration of a metal ion chelator like EDTA. The pH is adjusted to a mildly acidic range, and dissolved oxygen is minimized through techniques like sparging with inert gas. The solution is then packaged in a polymeric container under an inert atmosphere, and the entire package is sterilized via autoclaving. This process ensures that the epinephrine remains stable, with minimal degradation and isomerization, even after prolonged storage.

The differentiation from prior approaches lies in the combination of factors that contribute to stability without relying on traditional antioxidants. Previous attempts to stabilize epinephrine often involved antioxidants, which can cause allergic reactions, or complexing agents, which can complicate manufacturing and potentially reduce bioavailability. ’837 achieves stability through a synergistic effect of low epinephrine concentration, controlled pH, metal ion chelation , minimal dissolved oxygen, and appropriate packaging, resulting in a ready-to-inject solution with an extended shelf life and reduced risk of administration errors. The use of autoclaving for sterilization is also a key differentiator, ensuring sterility without significant degradation of the epinephrine.