Ternary solid–liquid phase diagram prediction and batch cooling crystallization applications for mannitol in synthetic and fermentation systems

• Solid-liquid equilibrium (SLE) modeling of mannitol for various ternary mixtures. • Studies with synthetic mixtures and lactic acid bacteria (LAB) fermentation broth. • Batch cooling crystallization of mannitol at various temperatures and compositions. • Analysis of mannitol crystals obtained from LAB fermentation broth. • Analysis methods used: NMR, HPLC, DSC, electrical conductivity, PXRD, and color. The production of mannitol using bio-based methods and its selective crystallization from fermentation broth depends on the synthesis route and the presence of relevant by-products and impurities. Raw materials such as glucose and glycerol can be fermented using Yarrowia lipolytica yeast strains to produce mannitol, with erythritol as the main by-product. However, variations in the ratio of mannitol to erythritol, influenced by feedstock quality, yeast strain, and process conditions, affect the conditions for selective mannitol crystallization as the purification step. In this study, the ternary phase diagram predicted via the UNIFAC-Larsen model with available readjusted parameters was used to evaluate crystallization routes, required temperature ranges, and maximum theoretical yield for selective mannitol crystallization from aqueous solutions containing different ratios of mannitol to erythritol. Based on this data, controlled batch cooling crystallization of mannitol was conducted, targeting 40 wt% theoretical yield from synthetic solutions with a mannitol:erythritol ratio of 1:1. The β-mannitol polymorph was identified in the crystalline product with a ratio of impurity mass fraction in crystals to feed of 0.2–0.45 at a cooling rate of 2 °C /h for different solution concentrations. In addition, cooling crystallization showed high selectivity toward mannitol produced by lactic acid bacteria using a mixture of fructose and glucose as a substrate. Nevertheless, a post-washing step is required to reduce the yellowness of the product and traces of impurities attributed to residual fermentation broth attached to the surface of the crystals.