Lactulose is a synthetic disaccharide composed of one galactose and one fructose molecule. It is used primarily as a sweetener in different products and as a functional food ingredient. It has been demonstrated to be a laxative, a prebiotic, hepatic encephalopathy and a prebiotic food additive [59, 74, 75]. Due to the increasing use of lactulose by the food and pharmaceutical industries, the interest in developing feasible industrial processes for the production of lactulose has prompted.

Lactulose can be produced either via semi-synthetic isomerization of lactose under alkaline conditions or by enzymatic isomerization and transgalactosylation reaction of lactose. Currently, lactulose is mainly produced via chemical isomerization. This process involves the presence of catalysts such as sodium hydroxide and boric acid. These catalysts help maximize the level of isomerization, minimize byproduct formation, and are environmentally safe and inexpensive. Large amounts of catalysts are needed to obtain high lactulose yields, which results in costly separation and purification steps [76]. Current research focuses on the development of catalysts that are environmental-friendly and lead to a minimum amount of byproduct formation [75].

Whey permeate is the main source for the industrial production of lactulose by chemical isomerization. The process involves isomerization of the glucose residue in the lactose molecule into fructose at alkaline pH values, which forms lactulose. This step is followed by a rapid degradation which leads to the formation of undesired byproducts including colored compounds which are difficult to remove from the lactulose solution [77]. Catalysts can be removed by chromatography or nanofiltration. Furthermore, isomerization leads to various breakdown products, such as galactose, epi-lactose, tagatose and fructose which must be separated to increase the lactulose yield and purity [78]. Depending on the catalyst used, yields vary from < 1% to 87%, with boric acid yielding 75% and calcium carbonate yielding only 20% [79].

The production via enzymatic isomerization is promising, as no chemical catalysts are needed. Lactose is hydrolyzed into glucose and galactose by the use of P-galactosidases. The galactosyl group, in the presence of fructose, is transferred to fructose, and lactulose is formed via rapid transgalactosylation [75]. Major challenges are the improvement of lactulose yield, purity, safety and process cost reduction. The yield of lactulose produced via enzymatic reaction depends on the origin of beta-galactosidase used, and are reported to be nearly 30% for enzyme isolated from Aspergillus oryzae [80].

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