(493a) Numerical Study on Mixing and Crystallization in an Impinging Jet Mixer

Numerical study on mixing
and crystallization in an impinging jet mixer

Jingcai Cheng¹, Chao Yang^1,2*, Zai-Sha Mao¹, Minghui
Xie³

¹Key
Laboratory of Green Process and Engineering, Chinese Academy of Sciences,
Beijing 100190, China

²University
of Chinese Academy of Sciences, Beijing 100049, China

³ Zhejiang Greatwall Mixers Co., Ltd, Wenzhou, Zhejiang 325019, China

*Corresponding authors. Tel: +86-10-62554558;
E-mail: chaoyang@ipe.ac.cn (C. Yang)

Abstract

Impinging jet mixers utilize high intensity micromixing
of fluids to achieve a homogenous distribution of high supersaturation before
the onset of nucleation. It
is recognized as one of the most reliable approaches to produce high quality
final product with desired size, narrow and unimodal particle
size distribution (PSD),
superior crystallinity and high purity [1].
Jet mixing is a relatively new field to the researchers in continuous
pharmaceutical manufacturing and some very recent studies have combined the jet
mixing crystallization with other processes such as cooling crystallization [2] or
other apparatuses such as stirred vessels and tubular reactors [3]. Experimental
works on mixing and crystallization in submerged [2] and non-submerged [1,4] jet mixers have been reported. Simulative works on precipitation and
antisolvent crystallization in confined (submerged mode) impinging jets were
reported [5-7]. Jet mixers operated in non-submerged mode could provide better
micromixing at lower Reynolds numbers possibly because of elimination of the entrainment
of the surrounding liquid [4].
However, no corresponding simulation work was reported. Various operating
conditions together with the crystallizer configuration
influence directly on the mixing condition, thus
the properties of crystal products, including crystal size distribution (CSD)
and also the polymorphic or pseudo-polymorphic form. Determination of optimal sets of operating conditions for desired
products by bench-scale experiments is time consuming and costly, and the
recipe for producing the desirable product might not be optimal after scale-up,
as the mixing effects and the spatial distribution of supersaturation can vary
vastly with the scale [8,9].
Thus, modelling is a good tool for obtaining desired
operating conditions, configurations and scale-up rules for mixing-sensitive
crystallization.

Very recently, we developed a coupled two-phase
flow-micromixing-PBE (population balance equation) model, where the micromixing
was described by the finite-mode PDF (probability density function) and the PBE
was solved by the generalized high-resolution finite-volume central-scheme [10]. A solver in the framework
of OpenFOAM (Open source field
operation
and manipulation) was developed, and applied successfully to
simulate the antisolvent crystallization (methanol-lovastatin-water) in an
impinging jet mixer operated in the submerged mode.

In this work, micromixing and mixing-sensitive
crystallization in both submerged and non-submerged jet mixers are
systematically investigated from the computational point of view. For the non-submerged
mode of jet mixing, a coupled three-phase flow-micromixing-PBE model is
developed for the first time, where the interface between the air and the
mixture of solution and crystal is captured by the volume of fluid (VOF) approach,
and the ¡°mixture phase¡± of the solution and crystal is described by the
two-phase CFD-micromixing-PBE model. The direct
quadrature method of moments combining with the interaction by exchange with the mean (DQMOM-IEM) micromixing model is adopted [11]. The DOMOM-IEM predictions are known in
good agreement with the full-PDF methods, and
it has
been widely adopted in recent years to simulate the effect of micromixing on chemical
reaction or precipitation[5, 6].

Corresponding solvers in the OpenFOAM are developed. We first simulate
the two-step Bourne reaction between 1-naphthol and diazosulfanilic acid,
operated both in submerged and non-submerged modes. Predicted results
(selectivity X) are compared with published data [4]. Then the antisolvent crystallization of
lovastatin in the impinging jet mixer operated both in
submerged and non-submerged modes is simulated. Predicted results of PSD are
compared with published experimental data. The influence of the configuration
and operating conditions such as inlet velocity, inlet concentration and
impinging angle on the micromixing characteristics and the product quality is
investigated. Also, the impinging jets operated in both modes are well compared
and analyzed. The present systematic investigation of micromixing and
crystallization in impinging jets will help in designing and scaling up jet
mixers and other processes combing jet mixing with stirred vessels or
tubular reactors.

Acknowledgements: Financial supports from National Natural Science
Foundation of China (21476236, 91434126), National Key Research and Development
Program (2016YFB0301702) and the Jiangsu National Synergetic Innovation Center
for Advanced Materials are gratefully acknowledged.

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