(120d) Developing a Robust Isolation and Drying Protocol for An API with Unique Physical Properties

The powder properties of APIs have the potential to impact downstream processing and affect the quality of the drug product. For this reason, it is important to deliver material with consistent physical characteristics for drug product manufacture. This requires that material attributes including form, particle size distribution and crystallinity be controlled throughout the isolation and drying processes of the API manufacture. The evaluation and design of isolation and drying unit operations is challenging due to their inherent sensitivity to scale. Performance can vary significantly as a function of equipment selection, geometry, and size. In addition, material behavior changes throughout the drying process, as wetted granular flows are often quite different from those of dried powders.

The present work describes a case study of a compound with unique material properties including a low melting point onset, potential for desolvation under shear, low bulk density and a propensity to bridge during solids conveying operations. This amplified the sensitivity of process performance to equipment configuration and scale. The phenomena observed at the pilot plant and manufacturing scales were not reproducible in the laboratory, so experimentation at manufacturing scale was required to develop an effective and robust isolation and drying protocol. Equipment selection, configuration and operating conditions along with the implementation of PAT were important factors in the development and ultimate success of the designed process. The developed process was demonstrated in numerous pilot plant batches and manufacturing scale trials. The final process was successfully transferred to a manufacturing site.