D2.292 - Epinephrine Nasal Powder - a sustainable and reliable option for the treatment of anaphylaxis

Orexo is developing OX640, a preservative-free nasal epinephrine powder formulation for treatment of anaphylaxis, designed to be stable across a wide temperature range and to have a prolonged shelf-life compared to liquid formulations. This work investigated stability of the powder formulation in comparison to a commercial autoinjector. From a sustainability perspective, OX640 offers potential advantages in terms of material use, expiration date, and waste reduction thanks to its novel powder formulation and needle-free design.

The OX640 formulation included 1 mg of epinephrine, along with trehalose, maltodextrin and sucrose laurate and was produced by an optimized spray-drying process. The powder was filled into a unidose nasal powder delivery system (Aptar Pharma, France) with a fill weight of 25 mg and placed in protective storage tubes with desiccant. Stability (epinephrine content, enantiomeric proportion and epinephrine degradation) of OX640 and the autoinjector was evaluated using HPLC-UV methods under accelerated storage conditions (40°C/75% RH) and under extreme conditions (50°C at ambient RH) for 6 months (OX640 only).

The spray-drying process yielded a free-flowing, rapidly dissolving powder with a narrow particle size distribution, optimal for nasal deposition (10-100 µm). OX640 exhibited minimal degradation and racemization of epinephrine for up to 12 months, whereas the autoinjector showed a decrease in assay from 105% to 73% and an enantiomeric purity of only 76%, resulting in a nominal dose of approximately 55% after 12 months, Figure 1. Even at 50°C, OX640 remained remarkably stable with less than 1% total degradation, still delivering the full dose without the need for antioxidants or preservatives, Table 1.

The OX640 epinephrine nasal powder provided superior stability compared to the autoinjector, providing for longer shelf-life and less strict storage conditions. This may benefit patients with risk of anaphylaxis by reducing the need for refills and ensuring access to effective, non-degraded medication when needed.