(265b) Continuous Operation of Zig-Zag® Blender for Pharmaceutical Applications | AIChE

(265b) Continuous Operation of Zig-Zag® Blender for Pharmaceutical Applications


Pernenkil, L. - Presenter, Massachusetts Institute of Technology
Cooney, C. L. - Presenter, Massachusetts Institute of Technology
Chirkot, T. - Presenter, Patterson Kelley and Company

Continuous blending of powders offers many advantages in terms of reduced capital investment, increased capital productivity, ease of process control and scale-up by number. In order to implement continuous blending in pharmaceutical manufacturing, a number of research questions need to be addressed. The question of the quality of mixture achieved with the FDA-set standard of mixture quality. Understanding the effects of operational parameters on blender performance is also important in optimizing blender operation. A zig-zag® blender was used to blend caffeine (as the active pharmaceutical ingredient) and lactose (as the Excipient) in a two component blending process. The total mass flow rate through the blender was fixed at 50 kg/hr and the angle of incline was fixed at 0. The external shell of the blender rotational speed was changed from 25 (0.25 m/s) to 50 (0.5 m/s) RPM while the intensifier bar rotation rate inside the drum section of the zig-zag® blender was changed from 1500 (8.5 m/s) to 3000 (17 m/s) RPM. Two Schenck Accurate continuous feeders were used to feed Caffeine and Lactose. The caffeine concentration in the feed was changed from 1 to 3 %. The blender performance was measured using variance reduction ratio (VRR) as the performance metric. VRR is defined as the input variance in the caffeine concentration coming from the feeder to the variance of the concentration observed at the outlet. A target VRR was defined based on half the FDA set limit of 6 % as the target relative standard deviation (RSD) in caffeine concentration that the blender is supposed to achieve at the outlet. Caffeine concentration was measured using Light Induced Fluorescence and dissolution assay using an UV spectrophotometer. Both the methods of analysis showed that the target VRR was achieved for 3% caffeine mixture ratio at higher intensifier bar speeds. The effect of intensifier bar rotation speed was the highest on VRR and was attributed to the fluidization mixing that the fast rotating tip brings about in the powder leading to better mixing while the shell rotation speed showed a non-linear effect and was attributed to its simultaneous effect on residence time and dynamic angle of repose. This work showed that continuous blending can conform to the target RSD set by FDA and that characterizing the effect of factors and relating them to the physics of the blending process is possible.


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