Practical Considerations for Spray Dried Formulation and Process Development

Abstract

Amorphous solid dispersion formulations provide a way to improve the bioperformance of poorly water soluble compounds by converting the crystalline drug to a high energy polymer stabilized amorphous state. Spray drying is a mature process with demonstrated production capability from lab to commercial scale for manufacturing amorphous solid dispersions. However, the impact of the drying process on the performance, manufacture, and stability of the drug product is often complex and can impact the chemical and physical stability of the drug, as well as the in vivo performance of the drug product. Physical and chemical properties of the components in the spray dried formulation can be linked to process risks. Analytical technology can build the connection between the process and the components of the formulation by measuring both the process dependent parameters and the product itself. Models can also be used to obtain a fundamental understanding of the system and be predictive of changes across process spaces. The properties of spray dried powder are amenable to multiple drug delivery routes such as oral suspensions and solid oral dosage forms. However, the process and environmental stresses put on the spray dried amorphous solid dispersions bring forth specific technical challenges. This chapter seeks to review the opportunities and failure modes associated with the spray drying process and the downstream fate of amorphous solid dispersions in several drug delivery routes while linking failure modes to the physical and chemical properties of the drug and formulation.