Unravelling the Cause of Epinephrine instability and rational Reformulation Studies

Epinephrine (or adrenaline) is the drug of choice for treatment of severe allergic reactions and anaphylaxis. From a chemical perspective, epinephrine is a highly unstable drug. The project entails a collaboration between the department of Pharmaceutical Technology and Biopharmacy of the University of Groningen and the pharmaceutical SME PureIMS to unravel the cause of epinephrine instability.

Allergic reactions to e.g. food allergens are posing an increasing problem in the Western world. Whereas in 2017 the probable diagnosed prevalent population in 8 major markets amounted to 7 million, only some 0.3 million subjects were treated, illustrating a vast unmet need. The current first-line emergency treatment of anaphylaxis consists of an intramuscular epinephrine injection administered in the thigh using an epinephrine autoinjector (EAI). Various issues and barriers withhold patients or their caretakers from correctly using their EAI or even using them at all. It has been reported that only 16% of adults who’ve been prescribed epinephrine know how to use the EAI correctly. There is thus a distinct need for an improved administration method of epinephrine in emergency situations.

Inhalable epinephrine is in clinical development. However, issues have been encountered with the stability of the drug product that need to be addressed. The aim of the current project is thus elucidating the root cause of the stability issues and subsequently develop a stable formulation of epinephrine for use in a dry powder inhaler.

Two promising formulations – stored under full moisture protection - are still physically and chemically stable after 9 months of storage under long-term (15-25 °C), intermediate (30 °C (± 2 °C)) and 6 months under accelerated (40 °C (± 2 °C)) storage conditions. At t=6 months the stability study under accelerated conditions was successfully completed, therefore, the stability data can be extrapolated to 18 months long-term stability. With that, it seems likely that the overarching goal of this project will be achieved.

Summary

Clinical research has demonstrated that epinephrine can be administered pulmonary through oral inhalation, enabling easier methods of administration of this drug compared to more invasive administration methods. Further research is required to unravel the cause of epinephrine instability with the objective to formulate a stable inhalable form of epinephrine.

Technology Readiness Level (TRL)

3 - 5

Time period

40 months

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