A novel approach to determine the granule density of milled ribbons using multi-stage air classification combined with dynamic image analysis
Determination of the granule density as a critical quality attribute during roller compaction/dry granulation provides an important parameter for further successful processing of the compacted materials. In this study, a novel approach was developed to determine the granule density using the principle of multi-stage air classifying. A roller compactor was utilized to produce ribbons and granules, composed of varying amounts of different excipients.
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Highlights
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Granule density via air classifying in combination with dynamic image analysis
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A material independent prediction model for the granule density was implemented
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Air classifying combined with dynamic image analysis can be used as effective PAT
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The dry granules were separated using an inhouse built multi-stage air classifier and analyzed via dynamic image analysis in terms of particle size distribution and shape, resulting in a material independent prediction model for the density of granules based on their separation behavior. Overall, the present study introduced a novel, continuous, non-destructive, and material independent method that provides the suitability to monitor the granule density with high accuracy, that can be used as potential process analytical technology for implementation into the roller compaction/dry granulation process.
Article Information: Tim D. Lillotte, Paul Bebernik, Karl G. Wagner. Powder Technology, 2020. https://doi.org/10.1016/j.powtec.2020.12.023.
Materials: Seven raw materials were used to produce dry granules. Microcrystalline cellulose (Vivapur® 101 and Vivapur® 105), α-lactose monohydrate (GranuLac® 200), dibasic calcium phosphate (DI-CAFOS® A150), isomaltose (GalenIQ® 800), D-Mannitol (Mannitol 35) and magnesium stearate (Ligamed®) were obtained from J. Rettenmaier & Sohne GmbH & Co. KG, Rosenberg, Germany, Meggle Group GmbH, Wasserburg, Germany, Chemische Fabrik Budenheim KG, Budenheim, Germany, BENEO GmbH, Mannheim, Germany, Roquette, Lestrem, France and Peter Greven GmbH & Co.KG, Bad Münstereifel, Germany. All materials are widely used in the pharmaceutical industry for the manufacturing and development of solid dosage forms. Raw material properties (d10, d50, d90, bulk density, tapped density, compressibility index) can be found in supplementary data.