In-line particle size measurement based on image analysis in a fully continuous granule manufacturing line for rapid process understanding and development

The present paper serves as a demonstration how an in-line PAT tool can be used for rapid and efficient process development in a fully continuous powder to granule line consisting of an interconnected twin-screw wet granulator, vibrational fluid bed dryer, and a regranulating mill. A new method was investigated for the periodic in-line particle size measurement of high mass flow materials to obtain real-time particle size data of the regranulated product.

The system utilises a vibratory feeder with periodically altered feeding intensity in order to temporarily reduce the mass flow of the material passing in front of the camera. This results in the drastic reduction of particle overlapping in the images, making image analysis a viable tool for the in-line particle size measurement of high mass-flow materials. To evaluate the performance of the imaging system, the effect of several milling settings and the liquid-to-solid ratio was investigated on the product’s particle size in the span of a few hours.

The particle sizes measured with the in-line system were in accordance with the expected trends as well as with the results of the off-line reference particle size measurements. Based on the results, the in-line imaging system can serve as a PAT tool to obtain valuable real-time information for rapid process development or quality assurance.

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Materials: The continuous granulation experiments were conducted using the placebo blend of α-lactose-monohydrate (Granulac® 70, Meggle Pharma, Wasserburg, Germany) and corn starch with a particle size between 15 and 100 µm (Roquette Pharma, Lestrem, France). The resulting premix had a bimodal distribution with a particle size of 121.5 µm (Dv50). The 27 w/w% solution of Polyvinylpyrrolidone (PVP) K30 (BASF, Ludwigshafen, Germany) in purified water was used as granulation liquid.

The comparison of the various particle sizing equipment was carried out using microcrystalline cellulose (MCC) pellets, which were produced in-house. The pellets were sifted using 300 and 500 µm mesh sieves (Retsch GmbH, Haan, Germany).

Article information: Lajos Madarász, Ákos Köte, Bence Hambalkó, Kristóf Csorba, Viktor Kovács, László Lengyel, György Marosi, Attila Farkas, Zsombor Kristóf Nagy, András Domokos, In-line particle size measurement based on image analysis in a fully continuous granule manufacturing line for rapid process understanding and development, International Journal of Pharmaceutics, 2021. https://doi.org/10.1016/j.ijpharm.2021.121280.