Application of Online NIR Spectroscopy to Enhance Process Understanding and Enable In-process Control Testing of Secondary Drying Process for a Spray-dried Solid Dispersion Intermediate

Near infrared spectroscopy (NIRS) was utilized to determine the endpoint of secondary drying process (post primary spray drying) of Spray-Dried Intermediates (SDI). In addition, NIR methods have been developed to quantify residual solvents (acetone and water), which are in-process controls (IPCs), and assay on the spray dried intermediate, thereby minimizing the need for off-line sample testing. NIRS calibration models were built with Partial Least Squares (PLS) regression for samples from several statistically designed experiments. Standard errors of prediction (SEP) of 0.1 wt. % for acetone, 0.2 wt. % for water, and 3.0 mg API/g SDI for API potency were obtained from validation of the models. When these methods were transferred to commercial scale on a different analyzer at a different site, additional updates to the NIR models were successfully made to overcome the impact from the differences in instrumentation and scale. Not only could real-time, in-process release be achieved, but also consistency and quality of data could be improved by minimizing or eliminating sample handling issues for off-line sample analysis. These NIR methods for secondary drying might also be used to optimize the drying process cycle time and study the effect of agitation rate, jacket temperature, and drying gas sweep rate on drying cycle time.