Different modes of dynamic image analysis in monitoring of pharmaceutical dry milling process

This article focuses on the process analytical technology (PAT) of pharmaceutical dry milling. The first objective is to compare different modes of dynamic image analysis namely, on-line, in-line and at-line for monitoring powder milling. The second objective is to introduce time evolving size and shape analysis (TESSA). Thus, a conical mill was equipped with a dynamic image analysis system which consisted of a xenon flash light and charge-coupled device (CCD) camera. Different pharmaceutical excipients and granulates were chosen as models. The results from the on-line, in-line and the at-line measurement modes showed similar size distributions for the various materials studied, however differences were observed that were mainly attributed to sampling and dispersion. A high correlation of 0.975 (p < 0.001) was observed between on-line d50 and at-line d50 when compared to 0.917 (p < 0.001) between in-line d50 and at-line d50. The concept of TESSA was found to be useful in detecting changes in milling conditions including the successful detection of a damaged screen when intentionally introduced in the milling process. This monitoring approach of particle size and shape has potential to reduce product variability, facilitates process development, and ultimately helps in establishing quality by design concept for the manufacture of solid dosage forms.