Epinephrine Nasal Powder – A sustainable and reliable option for the treatment of anaphylaxis

Purpose

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.

Methods

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).

Results

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 and 2. 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. SEM images can be seen in Figure 3.