Continuous lactose recovery from acid whey by mixed suspension mixed product removal (MSMPR) crystallizer in the presence of impurities

Darmali, Christine; Mansouri, Shahnaz; Yazdanpanah, Nima; Nagy, Zoltán K.; Woo, Meng Wai

doi:10.1016/j.cep.2021.108752

Cited by 2 publications

(3 citation statements)

References 57 publications

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“…Peristaltic pumps are often used to transfer the API solutions into crystallizers [15,28,29]. However, they require relatively long lines (>50 cm), which often clogged during operation, even when using tubing with an ID of only 1.42 mm.…”

Section: Choosing a Suitable Transfer Pump For The Addition Of The Mf...mentioning

confidence: 99%

Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer

Hansen

Kleinebudde

2022

Pharmaceutics

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Quasi-emulsion solvent diffusion (QESD) crystallizations can improve the micromeritic properties of drugs and excipients. A solution is dispersed in a miscible antisolvent as a transient emulsion. Using this technique, substances that normally crystallize in the form of e.g., needles, agglomerate into spherical, hollow particles. A disadvantage of QESD crystallizations is that the particle size of the agglomerates decreases with an increased solvent fraction of the mother liquor. Therefore, in batch production, many consecutive runs have to be performed, which is a time- and material-intensive process. The aim of this study was to convert a previously used lab-scale batch crystallizer into a mixed-suspension, mixed-product removal (MSMPR) crystallizer, since the batch size could be simply increased by increasing the run time of the system. The mean residence time (MRT) and solvent fraction in the system was predicted and verified using actual measurement curves. The experiments showed that >50 g QESD metformin hydrochloride could be crystallized in a single run, without observing a large shift in the particle size, while maintaining good flowability. Observations regarding the effect of the MRT on the particle size distribution could be verified for the production on a larger scale than previously described.

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Section: Choosing a Suitable Transfer Pump For The Addition Of The Mf...mentioning

confidence: 99%

Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer

Hansen

Kleinebudde

2022

Pharmaceutics

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“…A narrow PSD is relatively important in the crystallization process as it will later affect the downstream processes and hence, the product quality. For instance, a broad PSD will be challenging in the filtration process, resulting in the inefficiency of washing and agglomeration tendency …”

Section: Introductionmentioning

confidence: 99%

“…For instance, a broad PSD will be challenging in the filtration process, resulting in the inefficiency of washing and agglomeration tendency. 44 To answer these questions, batch crystallization of lactose was undertaken using the oscillatory DBC technique in this study. The MSZW was first measured at different initial supersaturated concentrations and cooling rates to explore the inherent operating space for lactose crystallization.…”

Section: Introductionmentioning

confidence: 99%

Strategy for Non-Seeded Crystallization of Slow-to-Crystallize Compounds with an Oscillatory Dynamic Baffled Crystallizer: A Case Study with α-Lactose Monohydrate

Darmali

Liu

Mansouri

et al. 2022

Org. Process Res. Dev.

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This study aims to evaluate a suitable operating strategy to produce slow-to-crystallize particles in the oscillatory dynamic baffled crystallizer (DBC) by taking a lactose compound as a case study. Metastable zone width (MSZW) determination experiments were conducted with three different supersaturated concentrations (0.6, 0.73, and 0.9 kg/kg solvent) at fast cooling (0.2 °C/min) and slow cooling (0.05 °C/min). A narrower MSZW was attained in the DBC than that in a stirred tank crystallizer due to the intensive mixing created by the oscillatory flow. The results showed that the DBC conditions evaluated at a higher initial supersaturation would allow fast cooling to approach the behavior of slow cooling. Such convergent behavior was observed in terms of the particle size distribution (PSD) and the resultant apparent MSZW. Despite the slightly lower yield attained with fast cooling, the significantly shorter required crystallization time would effectively allow higher production throughput than slow cooling. A high mixing intensity in the DBC showed that lactose crystallization was prone to secondary nucleation, which produced a broad PSD. A direct nucleation control (DNC) strategy was further adopted to push the boundary of the fast cooling−high initial supersaturation crystallization strategy. While the DNC strategy led to a narrower PSD and a similar high yield as the slow cooling−high initial supersaturation, the overall particle size was unexpectedly shifted to a relatively smaller range. These findings can be used as a basis to improve the lactose crystallization process by further investigating the secondary nucleation threshold of lactose in a DBC to attain larger crystals.

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Continuous lactose recovery from acid whey by mixed suspension mixed product removal (MSMPR) crystallizer in the presence of impurities

Cited by 2 publications

References 57 publications

Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer

Increasing the Batch Size of a QESD Crystallization by Using a MSMPR Crystallizer

Strategy for Non-Seeded Crystallization of Slow-to-Crystallize Compounds with an Oscillatory Dynamic Baffled Crystallizer: A Case Study with α-Lactose Monohydrate

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