Continuous blending monitored and feedback controlled by machine vision-based PAT tool.

In a continuous powder blending process machine vision is utilized as a Process Analytical Technology (PAT) tool. While near-infrared (NIR) and Raman spectroscopy are reliable methods in this field, measurements become challenging when concentrations below 2 w/w% are quantified. However, an active pharmaceutical ingredient (API) with an intense color might be quantified in even lower quantities by images recorded with a digital camera. Riboflavin (RI) was used as a model API with orange color, its Limit of Detection was found to be 0.015 w/w% and the Limit of Quantification was 0.046 w/w% using a calibration based on the pixel value of images. A calibration for in-line measurement of RI concentration was prepared in the range of 0.2-0.45 w/w%, validation with UV/VIS spectrometry showed great accuracy with a relative error of 2.53 %. The developed method was then utilized for a residence time distribution (RTD) measurement in order to characterize the dynamics of the blending process. Lastly, the technique was applied in real-time feedback control of a continuous powder blending process. Machine vision based direct or indirect API concentration determination is a promising and fast method with a great potential for monitoring and control of continuous pharmaceutical processes.