MXPA99008049A - A process for the crystallization of lactitol - Google Patents

Abstract

The present invention relates to a process for the production of structurally pure lactitol crystal forms selected from the group consisting of lactitol anhydride, lactitol monohydrate, lactitol dihydrate and lactitol trihydrate. The crystallization is performed by cooling a lactitol solution from a temperature at or slightly below the highest temperature of the stability area of the respective crystalline lactitol form to a temperature at or slightly above the lowest temperature of the stability area of said crystalline lactitol form, said stability areas being defined, respectively, within the temperature limits of 100°C and 0°C by the intersections of the solubility lines shown in Fig. 1, and by maintaining the supersaturation of said lactitol solution at a level of 1 to 8%(w/w) above the solubility line of the respective lactitol form crystallizing in said area.

Description

A PROCESS FOR THE CRYSTALLIZATION OF LACTITOL The present invention relates to a process for the production of crystalline forms of structurally pure lactitol. Especially, the invention comprises a process for the crystallization of lactitol from an aqueous lactitol solution as any of the crystalline lactitol forms chosen from the group consisting of lactitol anhydride, lactitol monohydrate, lactitol dihydrate and lactitol trihydrate.

Lactitol is a crude sweetener that can be used as a total or partial replacement of sucrose, however, its energy content is only half that of sucrose, and does not cause increased blood glucose content; in addition, he is kind to the teeth (see Developments in Sweeteners, Ed. Grenby, T.H., volume 3, 1987, page 65-81).

The preparation of lactitol from lactose has been known for a long time. Industrially, lactitol is prepared analogously with the preparation of sorbitol from glucose by hydrogenation in the presence of a nickel catalyst Raney. The preparation is described, for example, in Wolfrom, M.L., et al., J. Am. Chem.

Soc, 60, (1938) page 571-573.

It is reported that crystalline lactitol occurs in the anhydrous form (anhydride) as well as in the form of a monohydrate or dihydrate. Lactitol also crystallizes as a trihydrate. There seem to be more than one crystalline form distinct from at least the anhydride and the monohydrate. In crystallization, however, the most stable form generally crystallizes predominantly.

The crystalline lactitol monohydrate as well as the di- and trihydrate and the anhydride can be used as sweetening agents that look like sugar. For example, crystalline lactitol monohydrate can be used in dietetic products, confectionery, bakery products, cereals, desserts, hams, beverages, chocolate, mascar gum and ice cream. Lactitol crystals can also be used in the production of cosmetic products and in the manufacture of pharmaceuticals, such as toothpaste.

According to the aforementioned Wolfrom, et al. The lactitol anhydride article can be crystallized by adding ethanol to an evaporated lactitol solution at a high concentration. After a long crystallization time the crystals of lactitol anhydride which melt between 144 and 146 ° C were obtained.

The lactitol anhydride can also be crystallized from an aqueous solution as described in WO 92/16542, incorporated herein by reference. The process comprises cooling or evaporating a supersaturated lactitol solution at a temperature above 70 ° C to provide lactitol anhydride having a melting range of 149-152 ° C.

Anhydrous lactitol hydrate powders at a moisture content of less than 3% have been prepared by drying a solution of crystalline lactitol and hydrate at the same time. The hygroscopicity of these powders is used in the drying of wet mixtures (European Patent Application 0231643).

The crystallization of lactitol dihydrate is presumably mentioned for the first time by Senderens, J.B., Compt. Rend. 170, (1920), page 47-50. The lactitol solution obtained by the hydrogenation was slowly evaporated at room temperature so that the crystallization starts. The melting point of the resulting product was 78 ° C, and Senderens mistakenly considered it a monohydrate. However, it seems obvious from Wolfrom, ML, et al., J. Am. Chem. Soc. 74 (1952) page 1105 that the product obtained by Senderens was a dihydrate having a moisture content of 9.5%, determined by a Karl Fisher method, and a melting point between 76 and 78 ° C.

An attempt to prepare lactitol moñohydrate by crystallization was made in 1979, see van Velthuijsen, J.A., J. Agrie. Food Chem., 27 (1979) page 680. The product, however, was an impure hydrate structure containing 4.5% of other sugars.

Another attempt to crystallize lactitol monohydrate was made in 1981 as presented in European Patent 0 039 981. The inventors believed that they had obtained pure lactitol monohydrate with a melting point of 121-123 ° C. However, the crystallization was carried out at a constant temperature of 45 ° C or 20 ° C which, in fact, resulted in the precipitation of a mixture of lactitol structures and water. This product was then treated to provide crystals that melt between 110 ° C and 125 ° C. The temperature range indicates that the products were partially hydrolyzed forms of lactitol hydrate. The present applicant has found that it is not possible to produce structurally pure lactitol monohydrate by the processes described in said European patent.

EP 0 039 981 presents a process for the production of lactitol dihydrate by planting an aqueous lactitol solution with lactitol dihydrate and crystallizing at a constant temperature of between 10 and 25 ° C. The obtained dihydrates have a melting range of 78-83 ° C. According to said patent a lactitol solution provides monohydrate at 25 ° C if it is plated with monohydrate but dihydrate if it is plated with dihydrate. The foregoing is contrary to the discoveries of the present inventors. According to J. Kivikoski, et al., In Carbohydrate Investigation, 233 (1992) 53-59, the pure crystalline lactitol dihydrate is melted at 70-72 ° C, which indicates that the dihydrate product of the EP patent does not it was structurally pure lactitol dihydrate.

The preparation of lactitol trihydrate is described, for example, in Patent Application EP 0 381 483. The process comprises the crystallization of an aqueous lactitol solution or "solvent containing at a temperature of 0-30 ° C. According to the Examples, it uses a very high concentration of lactitol and obviously, in addition to lactitol trihydrate, a mixture of dihydrate and trihydrate may have been precipitated.The melting range of the product was 52-56 ° C. The structure of lactitol trihydrate has been presented in Carbohydrate Research, 233 (1992), 189-195.

In the crystallization process according to the invention presented in EP 0456636, the crystallization temperatures are in the range of 80 to 30 ° C and the crystallization is carried out as a cooling crystallization or as an evaporative crystallization. In the examples of said patent EP 0456636 the lactitol monohydrate of the cooling crystallization was recovered at about 40 ° C. since the faster cooling at the end of the crystallization and since the crystals present in the solution were pure lactitol monohydrate crystals, the product was pure lactitol monohydrate regardless of the fact that the temperature was lowered as much as 40 ° C or less.

The crystallization tests of said patent EP 0456636 showed that if the crystallization of lactitol monohydrate would occur in a controlled manner to obtain a desired crystal size without a wide distribution of crystal sizes, crystallization should be carried out in such a way that the supersaturation of the mother liquor remained below 1.3 (preferably 1.2) with respect to lactitol throughout the crystallization.

According to the application JP 13220/89 the lactitol monohydrate can be produced by crystallization at a temperature of 20-70 ° C to obtain a crystalline product that melts at 102-105 ° C.

The prior description of the prior art clearly shows that the crystallization of lactitol is a complicated matter, wherein a crystalline product obtained can be either a pure crystalline compound in the form of a pure anhydride, monohydrate, dihydrate or trihydrate, but the crystals also they may comprise mixtures of various lactitol structures and water. since the literature is full of contradictory statements regarding what ranges of temperatures and crystallization conditions provide that crystalline form, it is clear that the person skilled in the art would benefit from having an accurate tool to monitor the conditions in which crystallize one or the other of the pure crystalline forms.

Said precision tool for monitoring the crystallization of lactitol between 100 and 0 ° C is provided by the present invention, as defined in the appended claims.

The present invention provides the person skilled in the art with a means to solve the problem of knowing when a specific crystalline lactitol form can be easily and certainly crystallized from a lactitol solution. It provides a tool for the expert to monitor the temperature at any concentration in order to maintain supersaturation at an appropriate level above the solubility graph of the desired lactitol crystal form.

The specific temperature range for any of the crystalline forms is, according to the invention, provided by the intersections between the respective solubility lines of the adjacent crystalline forms and the solubility line of the desired crystalline form. The process of the invention allows those skilled in the art to be confident that the product produced will be structurally pure lactitol crystals of any specific form. The solubility plot presented for the first time also shows the restricted area, where the lactitol monohydrate is the stable crystalline form.

A specific feature of the present invention is that it provides a method for the crystallization of crystalline lactitol forms in a pure crystalline form apart from the others at a given temperature range chosen between 100 ° C and 0 ° C.

Thus, the present invention provides a process for the crystallization of lactitol from an aqueous lactitol solution having a lactitol purity of not less than 80% (on DS content), preferably 90% or higher. Crystallization provides structurally pure crystalline lactitol forms selected from the group consisting of anhydride, monohydrate, dihydrate and trihydrate upon cooling said lactitol solution of a temperature at or slightly below the highest temperature of the stability area of the lactitol form. crystalline corresponding to a temperature at or slightly above the lower temperature of the stability area of said crystalline form of lactitol, said stability areas are respectively defined within the temperature limits of 100 ° C and 0 ° C by the intersections of the solubility lines defined by the following equations (1) to (4): Anhydride: s /% = 59.6 + 0.3003 t / ° C Equation 1 Monohydrate: s /% = 50.2 + 0.4346 t / ° C Equation 2 Dihydrate: s /% = 39.7 + 0.6332 t / ° C Equation 3 Trihydrate 's /% = 33.4 + 1.1482 t / ° C Equation 4 s is the percentage of solubility of each respective lactitol form (weight / weight) calculated from the mass of lactitol and water as follows: weight of lactitol / (Weight of lactitol + weight of water) x 100%; t is the temperature in ° C; and by maintaining the supersaturation of said lactitol solution at a level of 1 up to 8% (weight / weight) above the solubility line of the respective lactitol form that crystallizes in said area.

Supersaturation is preferably maintained at the desired level of about 1 to 8% above the solubility equation by monitoring the temperature and lactitol concentration of the solution. Supersaturation is preferably maintained at 7% (w / w) or less. A supersaturation of only 1% will provide a very pure crystal, but the rate of crystallization is usually too slow for commercial purposes at such low supersaturation.

According to a preferred specimen, supersaturation is maintained at the desired level by monitoring the lactitol content of the lactitol solution and adjusting the temperature accordingly. The lactitol content can be monitored by measuring the refractometric index of the lactitol solution.

To ensure that the desired crystal form occurs from the start of crystallization and to increase the rate of crystallization, the lactitol solution is preferably seeded at the start of crystallization with small crystals of the crystalline lactitol form which is will crystallize in the respective stability area.

If desired, cooling the crystallization can be preceded by crystallization by evaporation to increase the production of the desired crystalline form. The temperature of the evaporation crystallization should preferably be kept well within the stability area of the crystalline lactitol form, more preferably about half of said stability area, while maintaining the supersaturation at 8% (w / w) ) or less.

The present invention also provides crystallization of structurally pure crystalline lactitol anhydride by cooling a lactitol solution having a lactitol purity of not less than 80% (on the DS content), preferably 90% or greater from a temperature at or slightly below 100 ° C to a temperature of or slightly above 69 ° C and by maintaining the supersaturation of said lactitol solution at a level of 1 to 8% (w / w) above the line of stability defined by the equation: s /% = 59.6 + 3003 t / ° C Equation 1 where: s is the respective solubility percentage of lactitol anhydride (weight / weight) calculated from the mass of lactitol and water as follows: Lactitol weight / (Lactitol weight + water weight) x 100%; t is the temperature in ° C; The resulting lactitol anhydride crystals are preferably recovered at a temperature above 66 ° C and dried to provide pure crystalline lactitol anhydride having a melting range of 146-152 ° C and a moisture content of 0-0.5. %.

The present invention also provides a process for the crystallization of structurally pure crystalline lactitol monohydrate by cooling a lactitol solution having a lactitol purity of not less than 80% (on the DS content), preferably 90% or higher from a temperature at or slightly below 69 ° C to a temperature at or slightly above 53 ° C and by maintaining the supersaturation of said lactitol solution at a level of 1 to 8% (w / w) above of the stability line defined by the equation: s /% = 50.2 + ~ 0.4346 t / ° C Equation 2 s is the percentage of solubility of respective lactitol monohydrate (weight / weight) calculated from the mass of lactitol and water as follows: weight of lactitol / (Weight of lactitol + weight of water) x 100%; t is the temperature in ° C; After crystallization the resulting crystals in any stability area should preferably be recovered at a temperature close to the lowest temperature of said stability area. For example, when lactitol monohydrate having a stability area of 69-53 ° C is produced, the crystals are preferably removed above 50 ° C. The above is done to make it easier to be sure that the recovered crystals are in fact monohydrate, without having to take extra precautions.

However, a person skilled in the art knows that in a crystallization process the crystal growth will preferably continue around the crystals already present in the solution. Therefore, in a cooling crystallization such as that described in EP 0 456 636 the monohydrate crystals will continue to grow below 53 ° C due to the mass of the pure monohydrate crystals in the solution. The crystallization at this stage should, however, not be prolonged and the cooling should be rapid.

The resulting lactitol monohydrate crystals are preferably dried to provide pure crystalline lactitol monohydrate with a melting range of 90-100 ° C and a moisture content of 4.9-5.1%.

The present invention also provides a process for the crystallization of structurally pure crystalline lactitol dihydrate by cooling a lactitol solution having a lactitol purity of not less than 80% (on the content DS), preferably 90% or greater from a temperature at or slightly below the 53 ° C to a temperature at or slightly above 12 ° C and maintaining the supersaturation of said lactitol solution at a level of 1 to 8% (w / w) above the stability line defined by the equation: s /% = 39.7 + 0.6332 t / ° C Equation 3 s is the percentage of solubility of the respective lactitol dihydrate (weight / weight) calculated from the mass of lactitol and water as follows: weight of lactitol / (Weight of lactitol + weight of water) x 100%; t is the temperature in ° C; The resulting lactitol dihydrate crystals are preferably recovered at a temperature above 12 ° C and dried to provide pure crystalline lactitol dihydrate with a melting range of 72 to 75 ° C and a moisture content of 9.4- 9-6%.

The present invention also provides a process for the crystallization of structurally pure crystalline lactitol trihydrate by cooling a lactitol solution having a lactitol purity of not less than 80% (on the DS content), preferably 90% or higher from a temperature at or slightly below 12 ° C to a temperature at or slightly above 0 ° C and by maintaining the supersaturation of said lactitol solution at a level of 1 to 8% (w / w) above of the stability line defined by the equation: s /% = 33.4 + - 1.1482 t / ° C Equation 4 s is the respective solubility percentage of lactitol trihydrate (weight / weight) calculated from the mass of lactitol and water as follows : weight of lactitol / (Weight of lactitol + weight of water) x 100%; t is the temperature in ° C; The resulting lactitol trihydrate crystals are preferably recovered at a temperature slightly above 0 ° C, and dried to provide pure crystalline lactitol trihydrate with a melting range of 38-45 ° C and a moisture content of 13.4-13.8%.

The water content of the crystals is preferably measured by the Karl Fisher method. The melting range is preferably measured by a melting point microscope.

An accurate determination of the melting range of lactitol crystals can not be carried out very successfully by introducing gently pressed glass samples into several capillary tubes and melting the open ends of the tubes before measuring. The measurements are carried out with a conventional melting point apparatus at different constant temperatures using a capillary tube by measurement until finding the extreme points of the melting range.

When determining the melting point, it must be taken into account that, for example, the melted lactitol monohydrate has a high viscosity in its melting temperature, so it takes time (up to 2 minutes) before the test is expanded uniformly on the walls of the capillary tube.

Due to its excellent technical and physiological properties, pure lactitol monohydrate is particularly suitable as a substitute for sugar, diabetic, dietetic or kindly products with teeth. When combining lactitol monohydrate with other raw or intense sweeteners, such as saccharin, Aspartame, Acesulfane K, Alitane, Sucralose, Stevioside or xylitol, a product that largely resembles sugar and yet has a higher energy content low and who is also kind with teeth can be prepared. This product can be used instead of sugar, for example, in sugar products, confectionery, hams, confectionery, tabletop sweeteners, cereals, desserts, chocolate, beverages, chewing gum and ice cream, as well as in products Pharmaceuticals and cosmetics, as is toothpaste.

Crystalline anhydrous lactitol is also suitable as a substitute for sugar in food products and sweeteners. Anhydrous lactitol can also be combined with other sweeteners such as saccharin and xylitol. Anhydrous lactitol is particularly suitable for the production of chocolate.

Lactitol dihydrate can also be used as a sweetener in food products, mainly in the same form as lactitol monohydrate and anhydrous lactitol. Due to its higher water content, lactitol dihydrate is slightly less hygroscopic than lactitol monohydrate. However, its lower melting point makes it useful in some applications, while lactitol monohydrate or lactitol anhydride may be more appropriate for some other uses.

The melting point of lactitol trihydrate is still lower than that of lactitol dihydrate, which reduces the uses for this sweetener. However, when low-melting non-hygroscopic crystalline lactitol is needed, then the trihydrate may well be the right choice.

The present invention provides a tool to know when any form of specific lactitol will crystallize from a given lactitol solution at a specific temperature range. It gives the expert the areas of stability that make it possible for the expert to produce pure crystals of the desired lactitol species. It provides a tool for the expert to monitor the temperature at any given concentration in order to maintain supersaturation at an appropriate level above the solubility graph of any form of lactitol hydrate or anhydride.

Determination of the solubility and stability of lactitol crystals in water was made as follows: Solubility Test 1 Materials and Methods Lactitol, which was used in the tests, was high grade lactitol monohydrate Lactitol MC (lot 21769) manufactured by Xyrofin OY, Finland according to patent EP 0456636. This monohydrate was also used as seed crystals. When the lactitol dihydrate was studied at 45 ° C and 55 ° C, the lactitol dihydrate produced in the applicant's research laboratory on December 20, 1994 (crystallization number 3) was used at the same time for the solution and as crystals of sow The water content of the lactitol dihydrate was 9.42% by weight by a Karl Fisher coulometric method. The water, which was used, was distilled water.

For the determination of solubility a solution with a supersaturation of 5 g / 199 g of solution was made. At 35 ° C the supersaturation was 10 g / 100 g. Also at the temperature of 5 ° C, 10 ° C and 15 ° C the supersaturation was 10 g / 100 g, because the supersaturation must be greater than the solubility of the monohydrate, which was used for the seeding. The solutions were made by dissolving the monohydrate in water at a temperature above the solubility temperature. The solutions that were used at 65 ° C and 75 ° C were made by evaporation with a vacuum rotary flask evaporator. The concentrations were determined by refractometry indexes (Rl). The weights of the solutions are shown in Table 1. At the temperatures of 5 ° C, 10 ° C and 15 ° C the solutions were made in a covered 2 liter container. The other solutions were made in 200 ml or 250 ml measuring bottles.

When the lactitol had dissolved, the solution was cooled to the temperature of the test. The solution was seeded with gently crushed monohydrate crystals (2 tests with dihydrate crystals). The weights of the sown crystals are illustrated in Table 1. In the measuring bottles the solutions were stirred with a magnetic stirrer and in the vessel covered with a motor-driven mixer.

TABLE 1 The weights of the components of the solutions h evaporated according to the Rl dih dihydrate The crystallization of lactitol and the equilibrium of the solution were monitored by measuring the refractometric index (Rl) of the mother liquid. Before taking a sample, the crystals are allowed to rest on the bottom of the container, so that the measurement of the Rl is as accurate as possible. The rest of the crystals was light due to the high viscosities of the lactitol solutions. A) Yes, the Rl of the mother liquor was measured from a suspension of crystals and solution. At the end point of the measurement the waiting time was not longer than the mother liquid was clearly separated and after the RI of the mother liquid was measured. The Ris were measured below 55 ° C with a refractometer from Index Instruments GPR-11-37 and above 55 ° C with a Zeiß refractometer, both were calibrated.

The equilibrium of the solution was usually monitored for 7 ... 14 days, but only for 3 days, when the dihydrate was used as seed crystals. At the end of the measurement the temperature of the solution was measured with a mercury thermometer, which had a measuring range of 0 ... 150 ° C and reading accuracy of 0.2 ° C. The accuracy of this thermometer was checked against a calibrated thermometer.

After the crystalline suspension had reached equilibrium, the crystals were separated by centrifugation for 15 minutes at 5000 rpm using a coarse cloth. A part of the crystals were dried at 60 ° C in a drying cabinet overnight. The water contents of both were dried and the dried crystals were analyzed by the Karl Fisher method or by a Karl Fisher coulometric method. In addition, casting behaviors were analyzed.

Results The final solubilities at the temperatures studied are shown in Table 2 and 3 in addition to the crystalline forms. The crystalline form was concluded from the water contents of the crystals without drying and from the melting ranges. The water contents are illustrated in Tables 4 and 5 and the fusion behaviors in Table 6.

Table 2 The equilibrium solubilities of lactitol and the crystalline forms of lactitol, when lactitol monohydrate was used as seed crystals.

Table 3 The equilibrium solubilities of lactitol and crystalline forms of lactitol, when lactitol dihydrate was used as seed crystals.

Table 4 Water contents of crystals as% by weight, when lactitol monohydrate was used as seed crystals. Temperature, ° C Water content,% 5.1 14.31 10.2 9.97 15.0 10.18 25.6 9.70 35.0 10.24 44.8 5.57 55.0 5.24 65.0 5.23 74.8 0.48 Table 5 Water contents of crystals as% by weight, when lactitol dihydrate was used as seed crystals.

Table 6 The melting point (m.p.) of the solubility test samples.

Test temperature, ° C m.p. ° C 5.1 _ 59.1-60.5 10.2 75-80 15.0 72.2-72.5 25.6 - 35.0 - 74.6-75.8 44.8 94.5-95.8 55.0 97.5-100.6 65.0 95.3-97.2 74.8 152-153.1 The solubility data in Table 2 were combined with some previous solubility measurement data. The curves of the solubility points were made as linear couplings, when% by weight was used as a unit of concentration. The solubilities of the hydrate forms in the crystallization areas were found to be almost linear. The couplings were made with the help of the Excel 5.0® spreadsheet program. The solubility equations of the different hydrate forms are illustrated in Equations from (I) to (IV): Anhydride: s /% = 59.55 + 0.3003 t / ° C Equation 1 Monohydrate: s /% = 50.21 + 0.4346 t / ° C Equation 2 Dihydrate: s /% = 39.67 + 0.6332 t / ° C Equation 3 Trihydrate s /% = 33.41 + 1.1482 t / ° C Equation 4 The coupling of the trihydrate can not be considered quite accurate because only three measuring points were used for coupling, an exact point, an uncertain point and a calculation point.

Conclusions The solubility points and the curve couplings are illustrated in a graph in Figure 1. It has been found that the curve couplings correspond well with the solubility points. From the intersections of the solubility curves it is possible to conclude the stability areas of the different forms of lactitol. The areas of stability of the different forms of lactitol are found to be: trihydrate: temperature < 12 ° C (not exact) dihydrate: 12 ° C < temperature < 53 ° C monohydrate: 53 ° C < temperature < 690C * anhydrous: temperature > 69 ° C when using seeded crystals, the amount of crystals sown and the speed of crystallization have an effect on the crystallization temperature areas, especially at the lower limits of the stability areas.

The following illustrative examples serve only to illustrate the work of the invention and should not be considered as boundary lines thereof.

Example 1 Cooling crystallization; lactitol monohydrate. A crystallization is carried out for pure lactitol monohydrate, starting from a filtered and deionized lactitol solution. The lactitol solution is prepared from a solution of hydrogenated lactose by the conventional technique.

The crystallization is carried out according to the following steps: A lactitol solution having a purity of about 98% lactitol in the dry matter is evaporated at 82% by weight at a temperature above 70 ° C and transferred in a conventional horizontal cylindrical batch-operated crystallizer provided with a mixer and a water recycling coating whose temperature is controlled by a microprocessor. The crystallization is carried out by controlling the cooling rate so that the supersaturation of the mother liquor does not exceed 8%.

In the crystallizer, the temperature of the solution is adjusted to 69 ° C, after which the solution is sown with crushed lactitol crystals of rnonohydrate. The size of the sown crystals is 0.02-0.05 mm, and the amount thereof is 0.004% by weight of the lactitol in the batch. After sowing, the dough is cooled in 10 hours to 53 ° C at a constant cooling rate, while the supersaturation is monitored by measuring the refractometric index (Rl). Supersaturation is maintained at no more than 5-7% above Equation number 2: s /% = 50.2 + 0.4346 f / ° C.

The crystals were separated from the mother liquor at a temperature above 50 ° C with a conventional basket centrifuge wherein the crystals were also washed using about 5% water per amount obtained from the crystalline product. The centrifuged crystals are dried with a drum dryer using the conventional technique. The production of lactitol monohydrate is about 40% by weight on the lactitol in the batch.

The resulting lactitol monohydrate crystals have a melting point of 94-98 ° C and a water content (Karl Fisher) of 5.0%.

The crystallization example 1 is intended to illustrate the practicability of the process according to the invention, but crystallization can also be carried out by modifying it in a manner as required by the normal effective production operation. Thus, crystallization can also be carried out without adding seeded crystals, that is, by allowing the solution to form seeds spontaneously. In addition, the crystallization can be carried out in combination with an evaporation crystallization as demonstrated in Example 2. Crystallization can also be carried out in a continuous operation as long as the temperature is maintained in the range of 69-53 ° C and the supersaturation of the mother liquor is kept below 8% (weight / weight).

Example 2 Crystallization of Cooling combined with evaporation crystallization. The crystallization of lactitol monohydrate is carried out by starting from a lactitol solution prepared by the hydrogenation as in Example 1. The solution is crystallized by evaporation for about 4 hours at 59 to 63 ° C, after which the crystallization mass is subjected to crystallization by cooling from about 63 ° C to 53 ° C as described in Example 1.

For the evaporative crystallization the lactitol solution is concentrated in a conventional evaporation crystallizer at a pressure of about 180 mbar at a dry substance content of about 81% by weight. The solution is seeded with lightly crushed lactitol monohydrate crystals. After sowing, more feed solution is supplied to the crystallizer, and the evaporation is continued at 59 to 63 ° C for about 4 hours. The resulting crystals are separated at 50.5 ° C and dried as described in Example 1.

The crystallization is carried out by controlling the evaporation and cooling to maintain the supersaturation of the mother liquor at not less than 8%.

The production of lactitol monohydrate is about 60% by weight on the lactitol in the batch. Lactitol monohydrate has a melting point of 94-98 ° C and a water content of 5.0%.

Example 3 Cooling crystallization; Anhydrous lactitol Nail lactitol solution containing about 98% lactitol on the dried solids is evaporated at a concentration of about 91% by weight at a temperature of about 95 ° C, and is transferred into an operated cooling crystallizer in conventional horizontal cylindrical batch provided with a mixer and a recycling water coating whose temperature is controlled by means of a microprocessor.

The cooling of the syrup starts at a rate of 10 ° C / 15 hours under agitation and then some crystals are formed. The cooling is continued until a temperature of 75 ° C after which the crystals are centrifuged, washed rapidly with water and dried with a fluidization dryer at about 65 ° C. The dried crystals are obtained at a production of around 30%. The melting point of the crystals is around 149 ° C to 152 ° C, the water content is 0.2%.

The crystallization can also be done in several steps, in which case a better production is obtained.

During cooling the supersaturation is monitored by measuring the Rl to ensure that the supersaturation does not fall below the solubility equation (Equation 1) for anhydrous lactitol. Supersaturation is maintained at no more than about 6-8% (w / w) above said equation.

Example 4 Cooling crystallization; Lactitol dihydrate The lactitol dihydrate is crystallized from lactitol syrup in 98.5% purity hydrogenated by cooling. Seeds of crushed lactitol dihydrate crystals are added at 50 ° C and cooling is continued up to 15 ° C. The crystals are centrifuged to provide a production of 52% and a crystal size of 0.9 mm. The crystals were dried at a temperature of about 50 ° C.

The crystals of lactitol dihydrate formed have a melting point of 70-72 ° C and a water content of 9.5%.

The supersaturation of the initial solution as well as the supersaturation during the cooling is monitored by measuring the Rl to ensure that the supersaturation does not fall below the solubility equation (Equation 3) for the lactitol dihydrate. Supersaturation was maintained at no more than about 6-8% (w / w) above said equation.

Example 5 Crystallization of Cooling; Lactitol trihydrate The lactitol trihydrate was crystallized from a lactitol solution having a purity of 98% by weight. Labeled crushed lactitol trihydrate crystal seeds are added to ° C and the cooling is continued until 0 ° C. The crystals are centrifuged to provide a 30% yield. The crystals were dried over MgSO4 and found to melt at 40-43 ° C. The water content is 13.6%.

The concentration of the initial lactitol solution as well as that of the solution during cooling is monitored by measuring the Rl to ensure that the supersaturation does not fall below the solubility equation (Equation 4) for lactitol trihydrate . Supersaturation is maintained at no more than about 6-8% (w / w) above said equation.

To increase the production, the cooling crystallization described above is repeated in several steps while the supersaturation is monitored.

Claims (14)

1. CLAIMS: 1. A process for the crystallization of lactitol from an aqueous lactitol solution having a lactitol purity of not less than 80% (on DS content), preferably 90% or greater, comprising the crystallization of forms of structurally pure crystalline lactitol chosen from the group consisting of anhydride, monohydrate, dihydrate and trihydrate upon cooling said lactitol solution of a temperature at or slightly below the highest temperature of the stability area of the crystalline lactitol form corresponding to a temperature at or slightly above the lower temperature of the stability area of said crystalline form of lactitol, said stability areas are respectively defined within the temperature limits of 100 ° C and 0 ° C through the intersections of the solubility lines defined by the following equations (1) to (4): Anhydride: s /% = 59.6 + 0.3003 t / ° C Equation 1 Monohydrate: s /% = 50.2 + 0.4346 t / ° C Equation 2 Dihydrate: s /% = 39.7 + 0.6332 t / ° C Equation 3 Trihydrate s /% = 33.4 + 1.1482 t / ° C Equation 4 s "is the percentage of solubility of each respective lactitol form (weight / weight) calculated from the mass of lactitol and water as follows: weight of lactitol / (Weight of lactitol + weight of water) x 100%; t is the temperature in ° C; and by maintaining the supersaturation of said lactitol solution at a level of 1 up to 8% (weight / weight) above the solubility line of the respective lactitol form that crystallizes in said area.
2. 2 A process according to Claim 1 wherein said supersaturation is maintained at the desired level by monitoring the percentage of lactitol in said lactitol solution and adjusting the temperature accordingly.
3. 3. A process according to Claim 2 wherein said lactitol content is monitored by measuring the refractometric index of said lactitol solution.
4. 4. A process according to Claim 1 wherein said lactitol solution is seeded at the start of crystallization with small crystals of the crystalline lactitol form to be crystallized in the respective stability area.
5. 5. A process according to Claim 1 wherein said cooling crystallization is preceded by a crystallization of evaporation at a temperature well within the stability area of the crystalline form of lactitol, while the supersaturation is maintained at 1 to 8% (weight / weight) or less.
6. 6. A process according to Claim 1 wherein crystals resulting from crystallization in any stability area are recovered at a temperature close to the lowest temperature and said stability area and dried.
7. 7. A process according to any of the preceding claims of the 1 to 6 comprising the crystallization of structurally pure crystalline lactitol anhydride by cooling said lactitol solution from a temperature at or slightly below 100 ° C to a temperature of or slightly above 69 ° C and at maintain supersaturation of said lactitol solution at a level of 1 to 8% (weight / weight) above the stability line defined by the equation: s /% = 59.6 + 3003 t / ° C Equation 1 where: s is the respective solubility percentage of lactitol anhydride (weight / weight) calculated of the lactitol mass and water as follows: weight of lactitol / (Weight of lactitol + weight of water) x 100%; t is the temperature in ° C;
8. 8. A process according to Claim 7 which comprises recovering the resulting lactitol anhydride crystals at a temperature above 69 ° C and drying them to provide pure crystalline lactitol anhydride having a melting range of 146-152 ° C. and a moisture content of 0-0.5%.
9. 9. A process according to any of the preceding claims of the 1 to 6 that includes crystallization of structurally pure crystalline lactitol monohydrate by cooling said lactitol solution from a temperature at or slightly below 69 ° C to a temperature at or slightly above 53 ° C and by maintaining the supersaturation of said lactitol solution at a level of 1 to 8% (weight / weight) above the stability line defined by the equation: s /% = 50.2 + 0.4346 t / ° C Equation 2 s is the percentage of solubility of respective lactitol monohydrate (weight / weight) calculated from the mass of lactitol and water as follows: weight of lactitol / (Weight of lactitol + weight of water) x 100%; is the temperature in ° C;
10. 10. A process according to claim 9 which comprises recovering the resulting lactitol monohydrate crystals at a temperature above 50 ° C and drying them to provide pure crystalline lactitol monohydrate having a melting range of 90-100 ° C and a moisture content of 4.9-5.1%.
11. 11. A process according to any of the preceding claims from 1 to 6 comprising the crystallization of structurally pure crystalline lactitol dihydrate by cooling said lactitol solution from a temperature at or slightly below 53 ° C to a temperature at or slightly above 12 ° C and by maintaining the supersaturation of said lactitol solution at a level of 1 to 8% (w / w) above the stability line defined by the equation: s /% = 39.7 + 0.6332 t / ° C Equation 3 s is the percentage of solubility of the respective lactitol dihydrate (weight / weight) calculated from the mass of lactitol and water as follows: weight of lactitol / (Weight of lactitol + weight of water) x 100%; t is the temperature in ° C;
12. 12. A process according to claim 11 comprising recovering the resulting lactitol dihydrate crystals at a temperature above 12 ° C and drying to provide pure crystalline lactitol dihydrate with a melting range of 72 to 75 ° C. and a moisture content of 9.4-9-6%.
13. A process according to any of the preceding claims from 1 to 6 comprising the crystallization of structurally pure crystalline lactitol trihydrate by cooling said lactitol solution from a temperature at or slightly below 12 ° C to a temperature at or slightly above 0 ° C and by maintaining the supersaturation of said lactitol solution at a level of 1 to 8% (w / w) above the stability line defined by the equation: s /% = 33.4 + 1.1482 t / ° C Equation 4 s is the respective solubility percentage of lactitol trihydrate (weight / weight) calculated from the mass of lactitol and water as follows: weight of lactitol / (Lactitol weight + water weight) x 100 %; t is the temperature in ° C;
14. 14. A process according to Claim 13 which comprises recovering the resulting lactitol trihydrate crystals at a temperature slightly above 0 ° C, and drying to provide pure crystalline lactitol trihydrate with a melting range of 38-45. ° C and a moisture content of 13.4-13.8%. EXTRACT OF THE INVENTION LaT present invention relates to a process for the production of structurally pure crystalline lactitol forms chosen from the group consisting of lactitol anhydride, lactitol monohydrate, lactitol dihydrate and lactitol trihydrate. The crystallization is carried out by cooling a lactitol solution from a temperature at or slightly below the highest temperature of the stability area of the respective crystalline lactitol form at a temperature at or slightly above the lowest temperature of the crystallization area. stability of said form of crystalline lactitol, said stability areas are defined, respectively, within the temperature limits of 100 ° C to 0 ° C by the intersections of the lines of solubility illustrated in Figure 1 and by maintaining the supersaturation of said lactitol solution at a level of 1 to 8 & (w / w) on the solubility line of the respective lactitol form that crystallizes in said area.