Spray dried Co-crystals of Itraconazole and Succinic acid for Inhalation Therapy

Hilke Lösing¹, Annette Bauer-Brandl² & Regina Scherließ¹

¹Department of Pharmaceutics and Biopharmaceutics, Kiel University, Kiel, Germany

²Department of Physics Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark

Summary

The number of lung infections, particularly those caused by fungal pathogens such as aspergillus, has increased significantly. However, many antifungal drugs, e.g., Itraconazole (a BCS Class II drug), have poor water solubility. This means that high oral doses are required to achieve therapeutic concentrations in the lungs and oral administration is often limited by poor bioavailability and systemic side effects. Inhalation therapy is a promising alternative administration route with its own formulation issues. The total dose that can be administered is limited and poorly soluble drugs are difficult to formulate. Additionally, inhalable formulations require particles with aerodynamic diameters of less than 5 µm. Using co-crystals is a promising way to improve solubility while maintaining a high drug content. Spray drying enables the production of inhalable particles within the desired size range for administering high doses directly to the lungs. In this study, a co-crystal of Itraconazole and Succinic acid was successfully produced using spray drying. Although an amorphous fraction is present in the formulation, it remained stable in the presence of water vapour. Recrystallisation occurred in the presence of ethanol vapour. By aerodynamic characterisation, it was shown that the spray dried co-crystal achieved a high fine particle fraction.