191x Filetype PPTX File size 0.18 MB Source: pharmahub.org
Scale-up Approach with Dimensional Numbers • The effect of process parameter (i.e., impeller speed, liquid addition rate) on the process and thus on granule characteristics are evaluated based on mechanistic understanding. • Use dimensional numbers as variables rather than individual process parameters. This will decrease the number of variables need to be varied, thus the number of experiments ( includes explicitly includes liquid addition rate, implicitly includes impeller speed and liquid addition mode). • Determine the design space at the smallest scale for the given formulation based on dimensional numbers and validate the design space for larger scales with less experiments compared to DOE approach. 100 Mechanical Crumb Dispersion 10-1 1 Intermediate f Nucleation Steady Growth p e 10-2 td Rapid S Growth 0.1 10-3 Drop Controlled Caking Induction 10-4 0.01 0.1 1 0 0.2 0.4 0.6 0.8 1 1.2 1.4 2 S a max Design of Scale-up Experiments Optimum conditions from Duquesne University Wet Granulation experiments: Liquid content :5 % Liquid addition rate :15 ml/min Impeller Speed :500 rpm Wet massing time :30 sec The liquid percentage is kept same as the smallest scale experiments. The sensitivity to liquid amount is tested around the optimum liquid level that was obtained at small scale. 3 Design of Scale-up Experiments • Ratio of fill height to granulator diameter at all scales should be kept constant. Granulator size 4 l 10 l 75 l Granulation Batch Size (kg) 0.6 1 9.72 Diameter of the granulator 17 24.6 52.5 bowl (cm) Fill height / Diameter 0.27 0.15 0.15 4 Design of Scale-up Experiments • The spraying time and the dimensionless spray flux need to be kept constant. 4 l = 0.11 For constant spraying time, the values for larger scales with single nozzle are calculated assuming 100 m drop size: 10 l = 0.15 and 0.18 (Close to small scale) 75 l = 0.34 and 0.50 (Too high compare to small scale, therefore higher amounts of lumps should be expected. Can be lowered by using two nozzles) 5 Design of Scale-up Experiments • Impeller speed was scaled according to constant tip speed and constant Froude number (Fr) rules (provided that the impeller speed is above the critical Froude number for constant tip speed rule. Constant Fr: Constant tip speed: N D N D 2 1 N: Impeller speed 2 1 N D D: Impeller diameter N D 1 2 1 2 4 l 10 l 75 l eed tip sp . 340 rpm t s on c eed sp 500 rpm . tip 195 rpm t ons c c o ns t. Fr 420 rpm c ons t. F 290 rpm 6 r
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