At that point, we can run a solution of the active ingredient through a miniaturized spray drying atomizer, allowing us to simulate atomization stresses and to quantify the impact of those stresses on the molecule. In order to minimize exposure of the material to thermal stresses, we can adjust the outlet conditions and use evaporative cooling if necessary. We can also minimize shear by selecting an appropriate pump and by optimizing atomization conditions.
This type of pre-feasibility screening requires only a few mL of API solution and usually provides good insight into whether spray drying is a good option.
Why spray dry when there are simpler methods of developing inhalable biologics?
Nebulization is currently the predominant method for the inhaled delivery of biologics, and biologics are available in liquid state; however, dry powder formulations offer a number of advantages over liquid formulation.
Compared to nebulized delivery of biologics, dry powder formulations:
- are more likely to be stable at room temperature
- require less storage space
- are more portable
- offer faster and more efficient delivery
- less likely to require stabilizers, surfactants, and other excipients
- can be free of preservatives
Alternative technologies for creating dry powder biologics, including spray-freeze drying and thin film freezing, may also hold promise. It is still early days for these, but they could have potential in future.
In the meantime, there is precedent for spray drying; the process is scalable; and spray drying can create particles optimized for inhalation.
How do development time and costs for spray dried biotherapeutics compare to small molecules?
As with any product, the development time and cost depend on many factors that cannot necessarily be predicted ahead of time. In general, though, a spray-dried biologic does not have to take longer to develop than a small molecule, though many aspects are different. For example, the analytical testing needed to assess the critical quality attributes of a biologic API differ substantially from a small molecule. Less regulatory guidance is currently available for inhaled biologic products. However, the field is developing rapidly as more candidates move through clinical trials.
