Wet nanomilling of naproxen using a novel stabilization mechanism via zirconium complexation

Maar, Scott; Damm, Cornelia; Peukert, Wolfgang

doi:10.1016/j.apt.2022.103723

Cited by 3 publications

(1 citation statement)

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“…When a brittle–ductile transition occurs, the grinding limit appears because below that size the relaxation mechanism changes from brittle fracture to ductile (plastic) flow [ 64 , 72 , 73 ]. Our estimate of the grinding limit, typically reported as a cumulant size, for drugs is in the range of 30–90 nm, based on previous studies [ 8 , 74 ]. In the current study, a transition particle size x * of 195 ± 20 nm (10.2% RSD) was estimated.…”

Section: Resultsmentioning

confidence: 99%

A Novel PBM for Nanomilling of Drugs in a Recirculating Wet Stirred Media Mill: Impacts of Batch Size, Flow Rate, and Back-Mixing

Heidari,

Muanpaopong,

Guner

et al. 2024

Pharmaceutics

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We examined the evolution of fenofibrate (FNB, drug) particle size distribution (PSD) during the production of nanosuspensions via wet stirred media milling (WSMM) with a cell-based population balance model (PBM). Our objective was to elucidate the potential impacts of batch size, suspension volumetric flow rate, and imperfect mixing in a recirculating WSMM. Various specific breakage rate functions were fitted to experimental PSD data at baseline conditions assuming perfect mixing. Then, the best function was used to simulate the PSD evolution at various batch sizes and flow rates to validate the model. A novel function, which is a product of power–law and logistic functions, fitted the evolution the best, signifying the existence of a transition particle size commensurate with a grinding limit. Although larger batches yielded coarser and wider PSDs, the suspensions had identical PSDs when milled for the same effective milling time. The flow rate had an insignificant influence on the PSD. Furthermore, the imperfect mixing in the mill chamber was simulated by considering more than one cell and different back-mixing flow ratios. The effects were weak and restricted to the first few turnovers. These insights contribute to our understanding of recirculating WSMM, providing valuable guidance for process development.

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