Inhalation powders come in many forms, including mixtures of micronized drug, excipient particles, micronized powders, or specially engineered particles. Regardless of the type, all are governed by complex inter-particle energies. Some of our sponsors work with Charles River early in the development lifecycle of their therapy, while others approach us during the exploratory discovery phases. Often, there is little known about the idiosyncrasies of the powders, the inter-particle energies, and therefore, how a powder behaves when generated as an aerosol. Each batch can be slightly different, as the production process is still being refined. The subtle but constantly changing characteristics of a test item (TI) are some challenges of inhalation toxicology.
The ability to measure the size of the particles of a powder, understand the type, and monitor how these energies/forces change over time offers new insights into generating these powders as aerosols for inhalation therapies and safety assessment studies. Our site in Edinburgh, UK has recently invested in a new Sympatec laser diffraction particle sizing instrument, which allows us to probe inter-particle energies using a dispersive energy titration (DET) method, which gives each powder a unique profile in terms of how easily particles can be aerosolized. Combined with our additional orthogonal tests for characterizing powders, we can use this information to identify the most fitting aerosol generator, to identify key challenges/risks with the powder prior to the study, and determine if special preparation of the powder is required, etc. This new offering enables the efficient, data-driven development of a bespoke aerosol characterization package prior to the start of the study.
Like all our tests, we recognize the challenges our sponsors face in terms of cost of goods (COGs) for their test items, so we use as little powder as possible (~100 mg for a full profile). The DET method has already been used to identify successfully risks/challenging characteristics in powders that could then be ameliorated, giving a more streamlined characterization program and dose administration during the in-life phase of the toxicology study. The method has been used to help our discovery sponsors select the most appropriate salt form of their drug, giving the greatest potential to be an inhalation therapy.