Continuous precipitation of L‐asparagine monohydrate in a micromixer: Estimation of nucleation and growth kinetics

Abstract

An experimental setup based on a static micromixer is used to determine nucleation and growth kinetics of L-asparagine monohydrate precipitated via antisolvent addition. Mixing in static micromixers was characterized previously using competitive-parallel reactions and computational fluid dynamics (Lindenberg et al., Chem Eng Sci. 2008;63:4135-4149). In this work, the mixer setup is used to determine nucleation and growth kinetics of L-asparagine at high supersaturations, i.e., true kinetics which are not affected by transport limitations. The method is based on measuring the particle size distribution obtained at different residence times. A population balance equation model of the process is used for the design of a continuous precipitation process. Finally, an analysis of the characteristic time scales of nucleation, growth, and mixing shows that, under the conditions in this study, mixing is much faster than precipitation and that the two processes can be decoupled. V V C 2010 American Institute of Chemical Engineers AIChE J, 57: 942-950, 2011

Determination of Nucleation and Growth Mechanisms of the B Polymorph of L‐Histidine by Induction Time Measurement

“…Up to now, numerous techniques for determination of the nucleation are available, and growth rates for the crystallization process have been proposed in the literature, e.g., methods using combined particle (crystal) counting and process time measurements [7,8], mixed-suspension mixedproduct removal (MSMPR) experiments in combination with particle size distribution (PSD) measurements [9,10], induction time measurements [11][12][13], and metastable zone experiments [14,15]. The most commonly applied method is induction time measurement [11][12][13].…”

Reactive Crystallization of Copper Selenide at Very High Supersaturation: A Challenge to Classical Crystallization Theory for Sparingly Soluble Salts

“…The geometry of the Y-mixer promotes rapid mixing down to the molecular scale, which is required before nucleation starts. The Y-mixer has been used successfully in previous studies [11,15,16] for measurement of nucleation rates of sparingly soluble salts.…”

“…There is currently no information on the nucleation kinetics of this system (or other extremely sparingly soluble systems). Therefore, an attempt was made to measure the nucleation kinetics experimentally, using the methods of Roelands et al [10] and Lindenberg and Mazzotti [11] as described in Garside et al [12]. The measured nucleation rates were then applied to calculate the kinetic constant A and the associated thermodynamic parameter B, fitting the plotted data to Eq.…”

Controlled seeding from multiple micromixers for tailoring the product size distribution in a semi-continuous crystallizer design

“…Lindenberg and Mazzotti [42] have modeled the precipitation of L-asparagine monohydrate in a Y-mixer assuming plug flow through the mixer. However, the intense mixing at the inlet in the DIJ chamber behaves more like a MSMPR [43].…”