Selective anomer crystallization from aqueous solution: Monitoring lactose recovery under mutarotation limitation via ATR-FTIR and theoretical rate analysis

Lactose is typically produced via cooling crystallization either from whey(-permeate) (edible-grade) or from aqueous solution (pharmaceutical-grade). While in solution, lactose is present in 2 anomeric forms, α- and β-lactose. During cooling crystallization under standard process conditions, only α-lactose crystallizes, depleting the solution of α-anomer. In practice, mutarotation kinetics are often assumed to be much faster than crystallization. However, some literature reports limitation of crystallization by mutarotation.

In the present research, we investigate the influence of operating conditions on mutarotation in lactose crystallization and explore the existence of an operation regimen where mutarotation can be disregarded in the crystallization process. Therefore, we study crystallization from aqueous lactose solutions by inline monitoring of concentrations of α- and β-lactose via attenuated total reflection Fourier-transform spectroscopy (ATR-FTIR). By implementing a linear cooling profile of 9 K/h to a minimum temperature of 10°C, we measured a remarkable increase in β/α-ratio, reaching a maximum of 2.19. This ratio exceeds the equilibrium level by 36%.

However, when the same cooling profile was applied to a minimum temperature of 25°C, the deviation was significantly lower, with a maximum β/α-ratio of 1.72, representing only an 8% deviation from equilibrium.We also performed a theoretical assessment of the influence of process parameters on crystallization kinetics. We conclude that mutarotation needs to be taken into consideration for efficient crystallization control if the crystal surface area and supersaturation are sufficiently high.

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Materials

Pharmaceutical-grade α-lactose monohydrate (purity ≥ 99%, ≥ 96% α-lactose) from Sigma Aldrich Inc., U.S.A., and β-lactose from Acros Organics B.V.B.A. (≥80% β-lactose) were used for all calibration experiments. For crystallization experiments coarse pharmaceutical-grade α-lactose monohydrate (purity ≥99.9%) was supplied by Meggle GmbH & Co. KG (Wasserburg, Germany) with the tradename SpheroLac 100. The anomer content in the lactose was determined using polarimetry. A detailed description of the method can be found in the appendix.”

Ramona Bier, Cornelia Eder, Simon A. Schiele, Heiko Briesen, Selective anomer crystallization from aqueous solution: Monitoring lactose recovery under mutarotation limitation via ATR-FTIR and theoretical rate analysis, Journal of Dairy Science, 2023, ISSN 0022-0302, https://doi.org/10.3168/jds.2023-23487

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