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.

Reference

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