Development of a methodology to estimate error in the on-line measurements of blend uniformity in a continuous powder mixing process

In this paper, a multi-point fiber optic based NIR system was implemented to monitor API concentration at the discharge of a continuous mixer. The sample size being interrogated by NIR was determined by measuring the velocity of the powder on the chute, which allowed selection of the number of scans to be averaged. A methodology was developed that allows quantification of the error associated with the in-line measurements. Comparison of in-line and off-line measurements was made at equivalent sample sizes. Mathematical model fitting for the in-line as well as off-line data revealed that the contribution of the analytical method error was negligible. A baseline RSD of 0.02 in the in-line measurements persists because of the inherent non-uniform nature of powder material. These results are useful towards achieving Real-Time-Release (RTR) of continuously manufactured drug product.

Graphical abstractThe sample size being interrogated by NIR in this system is proportional to the velocity of the powder on the chute, scanning time and number of scans to be averaged. A methodology was developed that allows quantification of the error associated with the in-line measurements. Comparison of in-line (NIR) and off-line (UV) measurements was made at equivalent sample sizes.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► On-line and off-line measurements of RSD were compared at equivalent sample sizes. ► The methodology provides a direct relationship between PAT and laboratory data.