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

https://doi.org/10.1016/j.jpba.2021.113902Get rights and content
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Highlights

  • Machine vision is utilized for the in-line measurement of colored drug content.

  • Digital camera-based PAT tool for continuous blending process.

  • Low Limit of Detection and Limit of Quantification.

  • Accurate drug content measurement in the 0.2−0.5 w/w% range.

  • Machine vision system can be used for feedback control of the blending process.

Abstract

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.

Keywords

Continuous blending
Machine vision
PAT
API content measurement
Feedback control
Colored API

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