Kimberly Shepard is Director, Respiratory Delivery, at Lonza
You presented a workshop at RDD 2023 subtitled, “From small molecules to all molecules” — can all biotherapeutics really be spray dried for inhalation?
Besides being a catchy title, “From small molecules to all molecules” captures the essence of what’s going on right now in the field of pharmaceutical spray drying. Although the only inhaled dry powder biologics that have been approved to date are spray dried insulin products, the Exubera DPI back in 2006 and Afrezza in 2014, work on spray drying many other types of biologics is underway.
While it’s likely that the pipeline contains some molecules that will prove too fragile for spray drying, we have already successfully spray dried more than 20 different biologics, and we are currently developing platforms for spray drying proteins, peptides, antibodies, and even RNA encapsulated within lipid nanoparticles.
How do you determine whether spray drying a particular biologic for inhalation will be feasible?
The main challenge to spray drying biologics results from the fragility of large molecules, which makes them vulnerable to the stresses encountered during spray drying such as shear and interfacial stresses during atomization and thermal stresses during droplet drying. Mitigating the stresses inherent in the spray drying process in order to maintain the integrity of these molecules requires significant expertise.
Before firing up the spray dryer, we can perform a number of tests to assess feasibility and risk using minimal amounts of material in a buffer solution. We are especially conscious of the need to use material-sparing approaches in our assessment of biologics, which cost significantly more to produce than small molecules.
Exposing small aliquots of solution to process-relevant temperatures and assessing changes to potency, morphology, or aggregation can be informative and materials-sparing. Differential scanning calorimetry (DSC) analysis allows us to determine the temperature where unfolding or degradation of the material begins to occur. If the molecule is stable at 60 C, for example, and does not begin to unfold until 65 or 70 C, then we consider the material to be a good candidate for spray drying.
