(700f) Developing a Roadmap to Effectively Spray Dry Biomolecules.

To date most of the biological therapeutics are delivered in either one of the two ways, via intravenous infusions or subcutaneous injections. However, these are no longer the preferred method of administration for these drugs as they are inconvenient and uncomfortable for some patients while limiting compliance of drug uptake. Moreover, with the current increase in demand for biologics on the market, there is a significant interest for finding innovative formulation and delivery approaches. However, formulating biologics brings many challenges as they are more complex and larger in size than the smaller molecule drugs. One of the major challenges of formulating the biological therapeutics is their increased risk of instability upon exposure to elevated temperatures or mechanical forces. One of the most common methods of increasing the stability of biologics is dehydrating the liquid formulations leading to improved long-term stability at increased temperatures and humidity due to lower molecular mobility and less intermolecular interactions. Freeze drying has been the most frequently used technique for solidification of biologics to date however, high energy consumption, large capital investment for infrastructure and long drying times have made it difficult to cope with the increased market demands.

On the other hand, spray drying is a one-step continuous process to produce dry powder from either a liquid or slurry through rapid drying using an inert gas at elevated temperatures. The spray drying process can potentially lead to particles most suitable for pulmonary delivery application (1-5 µm). The development of a spray drying process of biomolecules has been proven, to be challenging due to their sensitive nature. Additionally, these biomolecules are exposed to relatively high temperatures and atomisation shear forces that could lead to biomolecules denaturation.

This study was carried out on drying of lysozyme as a model biomolecule to investigate the effects of different atomising gas flow rates on its enzymatic activity and physicochemical properties. All samples were spray dried at 50ËšC outlet temperature, 1.5 ml/min feed rate and 473 L/hr, 601 L/hr and 742 L/hr atomisation gas flow rates; the inlet temperature increased slightly with an increase in atomisation gas flow rate. The applied shear stress during the atomisation process is a significant factor in determining the final stability of biomolecule that has been overlooked in previous research activities carried out on lysozyme.

The effect of atomisation gas flow rate on the residual bioactivity of lysozyme after spray drying can be seen in Figure 1. It has been shown that lysozyme in the solid form is increasingly deactivated as the atomisation gas flow rate increases. The lowest residual bioactivity of lysozyme was observed in samples sprayed at the highest atomisation gas flow rate (742 L/hr). On the other hand, samples atomised at the lowest atomisation gas flow rate (473 L/hr) showed the highest residual bioactivity (88%). These experiments show the direct implication of atomisation gas flow rate i.e. shear force on the denaturation of lysozyme. In addition, spray drying of lysozyme at various atomisation gas flow rates leads to the production of powders with particle sizes in the range of 4µm to 16 µm. Particle size distribution graphs show that powder C produced using higher atomisation gas flow rates lead to the smallest particle size of 4 µm and D50 of 8 µm, which suits best for pulmonary delivery applications. However, the low bioactivity of lysozyme at this level of atomisation gas flow rate due to high applied shear force needs to be addressed. The next phase of this project will be focused on addressing the stability challenge of biomolecules at high atomisation gas flow rates and achieving high proportion of fine particles (1-5 µm). These results have implications in changing the current biologics delivery methods i.e., intravenous, and subcutaneous injections with inhalable drug delivery methods. This could promote better patient compliance along with faster delivery outcomes.