(774c) Solid State Form Understanding Applied to the Design of a Spray Dried Dispersion Process: A Quality By Design Approach to Optimization of Feed Solution Loading

Spray drying is a common unit operation across many industries due to the ability to control bulk powder properties and isolate and dry product from a liquid feed in a single operation. For the pharmaceutical industry, spray drying offers the control of physical properties of crystalline or amorphous active pharmaceutical ingredients (APIs), as a neat or formulated drug product that can lead to improved bioavailability of the drug candidate. Drug candidate molecules are often formulated as a solid dispersion, incorporating both API and a polymer excipient for enhanced dissolution performance and improved physical stability. In order to reliably achieve solid form control to the amorphous state during the spray drying operation, the API must be fully solubilized in the spray dryer feed solution, eliminating crystalline API material. The crystalline form of the API may or may not be the most stable form in the selected spray drying solvent. To ensure robust solid state form control of the spray dried dispersion (SDD), not only should the form landscape of the API in the spray drying solvent be well understood the process control capabilities during feed solution preparation must be considered as well. Numerical modeling of the solubility of relevant API forms, in conjunction with feed solution loading and process control capability should be used to determine an optimal feed solution loading. The operating point can be selected through optimization based upon on selected risk-based criteria and control capability. Applying this methodology to Compound A, the throughput of the spray drying process was improved two-fold, while ensuring a robust control strategy to deliver the desired API in an amorphous form as a spray dried dispersion.