2021
DOI: 10.1021/acs.oprd.1c00209
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Abstract: This study compares the use of wet milling and indirect ultrasound for promoting nucleation and controlling the particle size during the continuous crystallization of a hard-to-nucleate active pharmaceutical ingredient (API). Both an immersion and an external wet mill installed on a recirculation loop were investigated. It was found that all methodologies significantly improved the nucleation kinetics, and the effects of key process parameters (e.g., mill speed, temperature, and ultrasound intensity) on partic… Show more

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Cited by 8 publications
(9 citation statements)
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“…Gassing crystallization hence poses a suitable alternative to the conventional method of seeding for controlling the crystallization process and can principally be operated in inert atmosphere by gassing with an inert gas. One advantage compared to other nucleation methods like sonication , or wet milling is the simple application without extensive additional equipment and less energy input to the system, by introducing the inert gas already present in the system into the solution. Here it should be noted that the choice of inert gas may affect the crystallization process, as studies by Ceyhan et al and Huang et al suggest, explained by the combined effects of dissolved gas on solubility and crystallization kinetics and changing properties of the gas–liquid interface.…”
Section: Introductionmentioning
confidence: 99%
“…Gassing crystallization hence poses a suitable alternative to the conventional method of seeding for controlling the crystallization process and can principally be operated in inert atmosphere by gassing with an inert gas. One advantage compared to other nucleation methods like sonication , or wet milling is the simple application without extensive additional equipment and less energy input to the system, by introducing the inert gas already present in the system into the solution. Here it should be noted that the choice of inert gas may affect the crystallization process, as studies by Ceyhan et al and Huang et al suggest, explained by the combined effects of dissolved gas on solubility and crystallization kinetics and changing properties of the gas–liquid interface.…”
Section: Introductionmentioning
confidence: 99%
“…Another problematic scenario is a wide MSZW, which makes it hard to control crystallization generating particles out of spec. External intervention such as sonication and milling can be used to induce nucleation . As pointed out in the previous literature, it can be very challenging to achieve desired physicochemical properties for the compounds in practice; the motivation of the current work is to review and summarize relevant strategies useful to meet these challenges.…”
Section: Key Process Parameters To Obtain Large Particle Sizesmentioning
confidence: 99%
“…39,40 It has been integrated into batch crystallizers to provide in situ breakage that promotes crystallization, 38,39,41,42 size reduction, and particle morphology control (e.g., alter the shape of a high-aspect-ratio crystal). 32,38,40,42,43 For example, Meng et al demonstrated a milling−dissolution−annealing approach to control the particle size distribution, where the wet mill configuration and milling speed were used to modify the mean particle size. 41 The breakage mechanism could also be used as a process intensification tool to help MSMPR crystallization overcome its complexity in process design and development.…”
Section: ■ Introductionmentioning
confidence: 99%