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.

The first important deliverable of this project will be a root cause analysis report in which the cause(s) of Epinephrine instability is elucidated. After this deliverable, different pharmaceutical formulations will be designed and investigated on stability. Ultimately a stability study will be conducted in which the proposed pharmaceutical formulation will be exposed to accelerated and long term storage conditions such that appropriate stability of inhalable epinephrine can be demonstrated.

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

Partners