WO2009140345A2

WO2009140345A2 - Buffer rinsed sucralose crystals

Info

Publication number: WO2009140345A2
Application number: PCT/US2009/043727
Authority: WO
Inventors: Warren L. Nehmer; Alexandria L. Bailey
Original assignee: Tate & Lyle Technology Ltd
Priority date: 2008-05-15
Filing date: 2009-05-13
Publication date: 2009-11-19
Also published as: AR071804A1; WO2009140345A3; TW201004971A

Abstract

A method of improving the stability of sucralose crystals includes washing the sucralose crystals with a solution of a buffer in a solvent, and subsequently drying the sucralose crystals. The method may be used in a sucralose manufacturing process, for example to help overcome sucralose stability problems resulting from long exposure of sucralose solutions to high temperatures.

Description

BUFFER RINSED SUCRALOSE CRYSTALS

BACKGROUND OF THE INVENTION

Sucralose (4,l',6'-trichloro-4,l¹,6'-trideoxy-galactosucrose), a high intensity sweetener made from sucrose, can be used in many food and beverage applications. Sucralose, unlike many artificial sweeteners, can be used in cooking and baking with no loss of sweetening power.

Sucralose may be made according to the procedures described in U.S. Pat. Nos. : 4,362,869; 4,380,476; 4,801,700; 4,950,746; 5,470,969 and 5,498,709, all of which are incorporated herein by reference. In all of these procedures, one of the final steps in the synthesis is a deacylation, typically deacylation of a sucralose-6- acylate such as sucralose-6-acetate or -benzoate, followed by crystallization of the sucralose. Laboratory scale methods for crystallizing sucralose have been described in U.S. Pat. Nos. : 4,343,934; 5,141,860; 4,977,254; 4,783,526; 4,380,476; 5,298,611; 4,362,869; 4,801,700 and 4,980,463, all of which are incorporated herein by reference. As is described in many of these patents, the deacylation of the sucralose precursor may be performed in methanol with a catalytic amount of sodium methoxide. After completion of deacylation the resulting sucralose solution is contacted with an ion exchange resin to convert the residual sodium methoxide to methanol. The ion exchange resin is then removed and the volatile solvents and reaction byproducts are removed by co-distillation with water, which results in a solvent switch to water. The mixture is decolorized by contacting with activated carbon. The carbon is removed to provide a decolorized sucralose solution suitable for crystallizing sucralose. The sucralose solution is concentrated to about 55 weight percent sucralose (at about 5O⁰C). The crystallization may be performed by reducing the temperature to about 22⁰C, and adding about 2 wt% of sucralose seed crystals. The resulting crystalline sucralose is separated from the mother liquor by centrifugation and then dried. The mother liquor that is separated from the crystals is added to the next batch just prior to decolorization. During the above process, especially over extended periods of time, impurities can accumulate that reduce the shelf life of the resulting sucralose crystals.

United States Patent No. 6,646,121 teaches methods of improving the storage stability of sucralose crystals by adding buffering agents such as sodium acetate to the mother liquor during crystallization, to control pH. Even with such steps, however, the mother liquor may still undergo some degree of degradation, and sucralose crystals recovered from degraded sucralose mother liquor typically show poor storage stability. This poor stability is manifested as an accelerated buildup of HCI resulting from sucralose hydrolysis, and also by color formation. Thus, sucralose stability problems are not completely solved in all cases by including buffers during crystallization, and methods of further improving the stability of sucralose crystals are still sought. SUMMARY OF THE INVENTION

In one aspect, the invention provides a method of improving the stability of sucralose crystals that includes washing the sucralose crystals with a solution of a buffer in a solvent and subsequently drying the sucralose crystals.

In another aspect, the invention provides a method of producing crystalline sucralose. The method includes the steps of: deacylating a sucralose-6-acylate to produce sucralose; recovering the sucralose as sucralose crystals; washing the sucralose crystals with a solution of a buffer in a solvent; and subsequently drying the sucralose crystals to form the crystalline sucralose. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows plots of pH drop as a function of time during accelerated storage testing of sucralose samples that had been post-degraded by rinsing with a degraded sucralose solution.

Figure 2 shows plots of pH drop as a function of time during accelerated storage testing of sucralose samples that had been crystallized from a degraded sucralose solution.

DETAILED DESCRIPTION OF THE INVENTION

The inventors have found that the storage stability of sucralose crystals may be improved by simply washing the crystals with a dilute buffer solution and subsequently drying the crystals to form the final product. As used herein, the term "buffer" refers to a salt of a weak acid. Sucralose crystals of good stability may be produced even from degraded mother liquor if they are subsequently rinsed with such a buffer solution. Similarly, although un-degraded sucralose crystals (referred to herein as "neat" crystals) of good stability that have subsequently been contacted with a degraded sucralose solution show very poor stability, good stability can be largely or even completely restored by rinsing the crystals with a dilute buffer solution according to the invention. Buffer Solutions

Suitable buffer solutions for use according to the invention may include solutions of salts of weak acids. Typically, the salts will be alkali metal salts. The weak acids may include phosphoric acid, carbonic acid, and carboxylic acids. Exemplary carboxylic acids include formic, acetic, propionic, maleic, fumaric, and benzoic acid. Suitable specific compounds include: sodium citrate or potassium citrate; sodium phosphate or potassium phosphate; amino acid bases such as arginine and lysine; sodium tartrate or potassium tartrate; sodium adipate or potassium adipate; sodium malate or potassium malate; sodium phosphate monobasic; and sodium phosphate dibasic. Also suitable are sodium or potassium ascorbate, caprylate, gluconate, lactate, and sorbate.

The buffer solution may be of any concentration that is effective to increase the stability of the sucralose crystals, and preferably will be low enough that it does not compromise the flavor or other properties of the sucralose. The concentration by weight will typically be at least about five (5) ppm, more typically at least about twenty-five (25) ppm, and most often will be at least about fifty (50) ppm. In some cases, the concentration is at least about one hundred (100) ppm. The concentration will typically be at most about ten thousand (10000) ppm, more typically at most about one thousand (1000) ppm, and generally will be at most about five hundred (500) ppm.

In some embodiments the buffer solution may contain only a solvent and the buffer salt itself, and in many embodiments the solvent will consist of water. However, the solvent may instead be any organic solvent suitable for food contact, or a mixture of one or more such solvents with water. Suitable exemplary organic solvents include ethyl acetate and ethanol. The buffer solution may also contain sucralose in any amount. In some embodiments, the buffer solution may be saturated or supersaturated with sucralose to minimize yield loss when the solution is used to wash the sucralose crystals.

It is notable that, even when sucralose is crystallized from a degraded sucralose solution, merely rinsing the crystals with a buffer solution according to the invention significantly increases stability. This is surprising, since the skilled artisan might have expected that crystals formed from a degraded solution would contain impurities throughout, and that any rinsing treatment would only reach the surface of such crystals and would thus not be expected to significantly improve stability. Nonetheless, the inventors have found that such a treatment is indeed very effective, as shown in the Examples. EXAMPLES

Degraded sucralose crystals were prepared in two different ways. In the first method, crystals were formed from a solution prepared from neat sucralose crystals, which solution had been purposely degraded by being held at high temperature for an extended time before forming crystals from it. Crystals formed from such a degraded solution are referred to herein as "degraded-as-formed" crystals. The second method involved purposely rinsing otherwise un-degraded (i.e., neat) sucralose crystals with a degraded sucralose solution. Crystals prepared in this manner are referred to herein as "post-degraded" crystals. Detailed descriptions of these procedures will now be given.

Preparation of Deqraded-As-Formed Sucralose Crystals

A control sample of commercial (neat) sucralose crystals was obtained from Tate & LyIe Technology Limited of Mclntosh, AL. A portion of the control sample was used to prepare a degraded sucralose solution from which degraded-as-formed crystals were prepared, all as follows. A 60% sucralose solution was prepared using 1,800 grams of the control neat sucralose crystals dissolved into 1,200 grams of deionized water. The resulting slurry was then heated to 7O⁰C to fully dissolve the sucralose crystals and then held at 7O⁰C to increase the concentration of degradation products and to lower the pH of the solution to a target pH of 2.5. This took approximately 24 hours, after which the solution was placed in a jacketed reactor. The temperature of the solution was equilibrated to 50⁰C and 1 gram of the control neat sucralose crystals was added to seed crystallization. The mixture was then cooled to 10⁰C and held at that temperature overnight. The resulting crystals were vacuum filtered and dried overnight in a vacuum oven at 35⁰C. A portion of the crystals was then ground to a smaller particle size using a mortar and pestle and further dried overnight on butcher paper. The final moisture content of the sample was less than 0.08% as determined by Karl Fischer titration.

Preparation of Post-Degraded Sucralose Crystals

A degraded sucralose solution was prepared by dissolving neat sucralose in deionized water to make a 60% solution. The solution was heated to 7O⁰C in order to get the sucralose to fully dissolve. The initial solution pH was approximately 5.8 and contained a minimal amouηt of degradation products. The solution was held at 7O⁰C for about 24 hours to increase the amount of degradation products and to decrease the pH of the solution to a target pH of 2.5. The solution was then slowly cooled to room temperature to form a supersaturated degraded sucralose solution. Approximately 500 grams of neat sucralose crystals was slurried into 1 liter of the supersaturated degraded sucralose solution at ambient temperature. The solution was stirred for 60 minutes and then filtered. The resulting cake was collected along with the filtrate. More of the supersaturated, degraded sucralose s rinsing solution was added to the filtrate until the volume was once again 1 liter. The resulting cake was then re-slurried into the 1 liter combined filtrate and rinse solution, stirred for 30 minutes and filtered. This process was repeated once more so that the sucralose crystals were rinsed a total of three times with the degraded solution. The final sucralose cake was then dried overnight in a vacuum oven heldo at 35⁰C. The sample was then ground to a smaller particle size using a mortar and pestle and further dried overnight on butcher paper in a fume hood. The final moisture content of the sample was less than 0.08% as determined by Karl Fischer titration.

Preparation of Buffer Rinse Solutions s A series of 50% neat sucralose solutions was prepared at sodium acetate concentrations of 0, 25, 50 and 100 ppm. In each case, this was done by adding 1,500 grams of neat sucralose to 1.5 liters of deionized water, along with the required amount of sodium acetate (if any). The mixture was heated to 50⁰C to fully dissolve the sucralose, and then cooled overnight to room temperature to form the0 sodium acetate/supersaturated sucralose rinse solution.

Treatment of Sucralose Crystals With Rinse Solutions

The degraded-as-formed sucralose crystals and the post-degraded sucralose crystals were each rinsed with each of the four rinse solutions (i.e., 0, 25, 50 and 100 ppm sodium acetate/supersaturated sucralose) according to the followings procedure.

Approximately 100 grams of the degraded sucralose crystals was slurried into 500 ml_ of the rinse solution. The mixture was stirred for 60 minutes and then filtered. The resulting filter cake was collected along with the filtrate. More of the rinse solution was added to the filtrate to bring the volume back to 1 liter, and the0 filter cake was re-slurried into that solution, stirred for 30 minutes and filtered. This process was repeated once more so that the initial sucralose crystals were rinsed a total of three times. The final sucralose filter cake was then dried overnight in a vacuum oven held at 35⁰C. The crystals were then ground to a smaller particle size using a mortar and pestle and further dried overnight on butcher paper in a fumes hood. The final moisture content of the sample was less than 0.08% as determined by Karl Fischer titration. Accelerated Storage Stability

Accelerated storage stability of the sucralose samples was assessed as follows. A sample of 20 ± 0.01 grams of each of the sucralose samples was put into an 8-oz. plastic screw top bottle and labeled as the Day 0 sample. Five separate

5 samples of 25 ± 0.01 grams of the sucralose samples are weighed into 6-oz. WHIRLPAK® polyethylene bags, available from Nasco of Fort Atkinson, WI. The 6-oz. WHIRLPAK® bags with the sucralose samples were then sealed twice using a bench-top heat sealer. Each bag was then placed into a larger WHIRLPAK® bag that was then sealed three times. The bags were labeled with the sample name and dayo of removal from oven. A large paper clip was pierced through the large WHIRLPAK® bag between the second and third seal and was used to hang the samples in the oven. The samples were then placed in a 50⁰C oven so that they did not touch the sides, bottom or other samples. Samples were removed from the oven after 3, 4, 5, 6 and 7 days of storage at 50⁰C. All of the samples were tested to evaluate color,s pH, moisture content, sucralose assay, amount of hydrolysis product, product consistency and odor.

The color of each sucralose sample was determined by measuring the yellowness index (YI) and the whiteness index (WI) values using a Hunter Color module, available from Hunter Associates Laboratory, Inc. of Reston, VA. Theo yellowness index value indicates how yellow a sample is, with higher YI denoting more yellow. The whiteness index value reports how color saturated a sample is. As the color of the sample increases further from white, the WI value decreases.

The pH of the sucralose sample was measured as follows. Water was pH-adjusted to a value of between 5.8 and 6.2, using deionized water, 0.1N 5 hydrochloric acid and 0.1N sodium hydroxide. The pH of the adjusted water was recorded. A sample of 5 ± 0.001 grams of dry sucralose was weighed into a 150 mL glass beaker. Then 50 mL of the pH-adjusted water was added to the sample. A magnetic stir bar was placed into the beaker and the beaker was covered with a watch glass. The mixture was stirred slowly for 3 minutes to assure that the0 sucralose was fully dissolved. The pH of the solution was then determined, and the drop in pH between the adjusted water and the solution was calculated and recorded. Samples having a pH drop of greater than 1.0 pH unit were considered to have failed the stability test.

Karl Fischer moisture determination was measured according to SER 2394.s Approximately 4 grams of sucralose was weighed out into a glass spoon. A Karl Fischer moisture titrator was calibrated and then pre-titrated for any excess moisture present. The sample was then added to the titrator and was completely dissolved in anhydrous Karl Fischer grade methanol, after which it was automatically titrated using 0.2mg/ml_ Karl Fischer reagent.

The odor and consistency of the samples were determined 24 hours after they were taken out of the oven and put into the sample container. Since this test typically produces samples that on Day 0 are free-flowing and have no chlorine odor, the descriptions of subsequent day samples noted herein are reported by comparison with the Day 0 samples.

Sucralose Assay Sucralose concentration was quantified using a reverse phase high performance liquid chromatograph with a differential refractive index detector, using an acetonitrile/water (15:85) mobile phase.

Sucralose Decomposition - Hydrolysis Product

The level of sucralose decomposition was assessed via determination of the decomposition product 4-chlorogalactose (4CG) by High Pressure Anion Exchange with Pulsed Amperometric Detection (HPAE-PAD). The analysis was performed using a Dionex GP50 gradient pump and ED40 electrochemical detector equipped with a gold electrode, coupled to a Dionex Carbopac PAl column set and using a sodium hydroxide and sodium acetate eluent. Test results for sucralose samples are shown in the following tables, where

NaAc indicates sodium acetate and a negative number indicates a drop in pH. When the pH drop of a given sample was more than -1.00, the sample was judged to be no longer acceptable. Table 1 shows data for the post-degraded samples and the neat (control) sample, and Table 2 shows the data for the degraded-as-formed samples. Figure 1 plots pH drop as a function of time for the post-degraded samples, and Figure 2 plots the pH drop for the degraded-as-formed samples.

As the data in the Tables and Figures reveal, degraded-as-formed sucralose crystals (Run 7) had extremely poor stability. Rinsing these crystals with the 0 ppm NaAc (i.e., no buffer) sucralose solution (Run 8) had little effect on the stability of the crystals, but stability improved significantly with the 25 ppm rinse (Run 9) and continued to improve with the 50 ppm and 100 ppm rinses (Runs 10 and 11, respectively).

The post-degraded sample (Run 2) also had very poor stability, showing a precipitous pH drop during the test. Its stability was nearly as bad as that of the degraded-as-formed crystals of Run 7. However, rinsing this sucralose sample with the 0 ppm NaAc sucralose solution (Run 3) produced a significant improvement, and the improvement continued steadily as increasing concentrations of NaAc were used until, at 100 ppm NaAc (Run 6), the stability was virtually indistinguishable from that of the control sample (Run 1).

As disclosed in U.S. Pat. No. 6,646,121, the addition of sodium acetate during sucralose crystallization may reduce deterioration of the sucralose and thereby reduce stability problems with the resulting crystals. The effectiveness of this method appeared to depend upon preventing the formation of decomposition products, and it was not believed that good product could be produced if decomposition had already occurred. The inventors have now found, however, that even if low-stability sucralose crystals are produced (e.g., from a degraded sucralose solution), their instability can be largely reversed by rinsing with a solution containing a buffer. This is wholly unexpected and of great practical benefit, since it allows the recovery of sucralose of excellent quality from solutions that had previously been considered unusable due to having suffered significant degradation.

Although the invention is illustrated and described herein with reference to specific embodiments, the invention is not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims without departing from the invention.

Claims

What is Claimed:

1. A method of improving the stability of sucralose crystals, comprising washing the sucralose crystals with a solution of a buffer in a solvent and subsequently drying the sucralose crystals.

2. The method of claim 1, wherein the solution comprises from 5 ppm to 10000 ppm of the buffer.

3. The method of claim 1 or 2, wherein the solution comprises at least 25 ppm of the buffer.

4. The method of any preceding claim, wherein the solution comprises at least 50 ppm of the buffer.

5. The method of any preceding claim, wherein the solvent is water.

6. The method of any one of claims 1-4, wherein the solvent is ethanol or ethyl acetate.

7. The method of any preceding claim, wherein the buffer is a salt of a carboxylic acid.

8. The method of claim 7, wherein the carboxylic acid is acetic acid.

9. The method of any preceding claim, wherein the solution of the buffer further comprises sucralose.

10. The method of any preceding claim, wherein the solution of the buffer is saturated or supersaturated with sucralose.

11. Sucralose crystals prepared by the method of any preceding claim.

12. A method of producing crystalline sucralose, comprising the steps of: deacylating a sucralose-6-acylate to produce sucralose; recovering the sucralose as sucralose crystals; washing the sucralose crystals with a solution of a buffer in a solvent; and subsequently drying the sucralose crystals to form said crystalline sucralose.

13. The method of claim 12, wherein the solution comprises from 5 ppm to 10000 ppm of the buffer.

14. The method of claim 12 or 13, wherein the solution comprises at least 25 ppm of the buffer.

15. The method of claim 12 or 13, wherein the solution comprises at least 50 ppm of the buffer.

16. The method of any one of claims 12-15, wherein the solvent is water.

17. The method of any one of claims 12-16, wherein the buffer is a salt of a carboxylic acid.

18. The method of claim 17, wherein the carboxylic acid is acetic acid.

19. The method of any one of claims 12-18, wherein the solution of the buffer further comprises sucralose.

20. Crystalline sucralose prepared by the method of any one of claims 12- 19.