Continuous Mixing Technology: Characterization of a Vertical Mixer Using Residence Time Distribution

Lee, Kai T.; Kimber, James A.; Cogoni, Giuseppe; Brandon, Jenna K.; Wilsdon, David; Verrier, Hugh; Grieb, Sally; Blackwood, Daniel O.; Jain, Ashwinkumar C.; Doshi, Pankaj

doi:10.1016/j.xphs.2021.01.035

Cited by 9 publications

(4 citation statements)

References 19 publications

(26 reference statements)

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“…Note that the residence time distribution for a given particle during a PCMM process could be anywhere from a few seconds to up to 10−20 min. 9,28 These results confirmed our first hypothesis�during the CMT operation, APIs existing as hydrates may undergo dehydration. The vigorous mixing, coupled with the continuous nitrogen purge, seems to have facilitated dehydration.…”

Section: Discussionsupporting

confidence: 83%

“…The rapid dehydration in this time scale is of importance considering the practical residence time of particles during continuous mixing and points toward the need of monitoring the solid form during CM operations. Note that the residence time distribution for a given particle during a PCMM process could be anywhere from a few seconds to up to 10–20 min. , These results confirmed our first hypothesisduring the CMT operation, APIs existing as hydrates may undergo dehydration. The vigorous mixing, coupled with the continuous nitrogen purge, seems to have facilitated dehydration.…”

Section: Discussionsupporting

confidence: 82%

“…The PCMM system consists of (i) gravimetric feeders, (ii) an in-line powder mixer [referred to as continuous mixing technology (CMT)], (iii) a rotary tablet press, (iv) an in-line near-infrared system (for continuous process monitoring), and (v) tablet metal detector and deduster . The CMT features two rotating impellers stacked on top of each other in a cylindrical vessel with a conical section at the bottom . Powder material flows vertically through the CMT, wherein the top impeller breaks up agglomerates, and subsequently, the bottom impeller ensures mixing .…”

Section: Introductionmentioning

confidence: 99%

“…2 The CMT features two rotating impellers stacked on top of each other in a cylindrical vessel with a conical section at the bottom. 9 Powder material flows vertically through the CMT, wherein the top impeller breaks up agglomerates, and subsequently, the bottom impeller ensures mixing. 10 This ensures homogeneous mixing of the active ingredient and excipients under an atmosphere of nitrogen.…”

Section: Introductionmentioning

confidence: 99%

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Drug Phase Transformation and Water Redistribution during Continuous Tablet Manufacturing: A Case Study of Carbamazepine Dihydrate

et al. 2023

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In recent years, continuous tablet manufacturing technology has been used to obtain regulatory approval of several new drug products. While a significant fraction of active pharmaceutical ingredients exists as hydrates (wherein water is incorporated stoichiometrically in the crystal lattice), the impact of processing conditions and formulation composition on the dehydration behavior of hydrates during continuous manufacturing has not been investigated. Using powder X-ray diffractometry, we monitored the dehydration kinetics of carbamazepine dihydrate in formulations containing dibasic calcium phosphate, anhydrous (DCPA), mannitol, or microcrystalline cellulose. The combined effect of nitrogen flow and vigorous mixing during the continuous mixing stage of tablet manufacture facilitated API dehydration. Dehydration was rapid and most pronounced in the presence of DCPA. The dehydration product, amorphous anhydrous carbamazepine, sorbed a significant fraction of the water released by dehydration. Thus, the dehydration process resulted in a redistribution of water in the powder blend. The unintended formation of an amorphous dehydrated phase, which tends to be much more reactive than its crystalline counterparts, is of concern and warrants further investigation.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 82%