PROPYL GALLATE-CONTAINING VITAMIN PREPARATIONS

Abstract

The present invention relates to a pulverulent vitamin formulation in which the vitamin essentially has a particle size of less than 0.7 m and which comprises an effective amount of propyl gallate, and also to processes for producing this formulation, and to formulations obtainable by these processes and to the use thereof as animal feed, food, food supplement, personal care product or pharmaceutical composition. The formulations of the invention have improved stability compared to the prior art.

Claims

1.-23. (canceled)

24. A pulverulent vitamin formulation in which the vitamin essentially has a particle size of less than 0.7 m, wherein said formulation comprises an effective amount of propyl gallate.

25. The pulverulent vitamin formulation according to claim 24, wherein the effective amount used is 3.5% to 9.5% by weight of propyl gallate based on the total amount of the formulation, where the weight ratio of propyl gallate to vitamin in the production is between 0.21 and 2.63.

26. The pulverulent vitamin formulation according to claim 24, wherein the vitamin is selected from the group consisting of vitamins D, E, K or Q or derivatives thereof.

27. The pulverulent vitamin formulation according to claim 24, wherein the formulation comprises butylhydroxytoluene or synthetic and/or natural tocopherol.

28. The pulverulent vitamin formulation according to claim 27, wherein the tocopherol is natural tocopherol.

29. The pulverulent vitamin formulation according to claim 27, wherein propyl gallate and tocopherol are present in the formulation in a ratio of 9:1 to 1:2.

30. The pulverulent vitamin formulation according to claim 27, wherein propyl gallate and butylhydroxytoluene are present in the formulation in a ratio of 8:1 to 1:4.

31. The pulverulent vitamin formulation according to claim 24, wherein the quotient therein of active vitamin (A2/A1) in relation to a comparative sample that comprises, rather than propyl gallate, the same amount of ethoxyquin (B2/B1), after 4 weeks in a stress test, is at least 0.75, where the proportion of active vitamin is ascertained by weighing 100 mg in each case of the formulation produced and 4 g of a mixture of 50% by weight of fine lime (<1000 m), 20% by weight of wheat bran (<1000 m), 20% by weight of 50% silica-supported choline chloride (<1000 m) and 10% by weight of trace element mixture (100-500 m), said trace element mixture consisting of 46.78% by weight of FeSO.sub.4x7H.sub.2O (100-500 m), 37.43% by weight of CuSO.sub.4x5H.sub.2O (100-500 m), 11.79% by weight of ZnO (<500 m), 3.61% by weight of MnO and 0.39% by weight of CoCO.sub.3 into 50 mL glass containers, mixing the ingredients and storing them in a climate-controlled chamber at 40 C. and 70% humidity for 4 weeks, with determination of the vitamin content (A1) and (B1) prior to commencement of the storage and of the vitamin content (A2) and (B2) on conclusion of the storage, calculating the proportion of active vitamin from the quotient A2/A1 and B2/B1.

32. A process for producing finely divided, pulverulent vitamin formulations in which the vitamin essentially has a particle size of less than 0.7 m, comprising the steps of a1) dissolving the vitamins in a volatile, water-miscible organic solvent or in a mixture of water and a water-miscible organic solvent at temperatures between 50 C. and 200 C., optionally under elevated pressure, within a period of less than 10 seconds, a2) rapidly mixing the solution obtained after a) with an aqueous or colloidally dispersed solution of a colloid at temperatures between 0 C. and 50 C., with precipitation of the vitamin in colloidally dispersed form, a3) converting the dispersion formed to a dry powder by removing the majority of solvent and then drying, or a2) dissolving the vitamins in a volatile, water-immiscible organic solvent at temperatures of 30 to 150 C., optionally under elevated pressure, b2) mixing the solution obtained after a) with an aqueous or colloidally dispersed solution of a colloid, forming an emulsion, c2) removing the organic solvent from the emulsion and converting the suspension/dispersion formed to a dry powder by removing the water and then drying, or a3) converting the vitamin to a liquid by heating above its melting point or dissolving it in an oil or incubating it at room temperature, b3) mixing the melt obtained after a3) with an aqueous or colloidally dispersed solution of a colloid, forming an emulsion, c3) converting the dispersion formed to a dry powder by removing the water and then drying, wherein the process is conducted in the presence of an effective amount of propyl gallate.

33. The process according to claim 32 for producing finely divided, pulverulent vitamin formulations in which the vitamin essentially has a particle size of less than 0.7 m, comprising the steps of a1) dissolving the vitamins in a volatile, water-miscible organic solvent or in a mixture of water and a water-miscible organic solvent at temperatures between 50 C. and 200 C., optionally under elevated pressure, within a period of less than 10 seconds, b1) rapidly mixing the solution obtained after a1) with an aqueous or colloidally dispersed solution of a colloid at temperatures between 0 C. and 50 C., with precipitation of the vitamin in colloidally dispersed form, c1) converting the dispersion formed to a dry powder by removing the majority of solvent and then drying, or a2) dissolving the vitamins in a volatile, water-immiscible organic solvent at temperatures of 30 to 150 C., optionally under elevated pressure, b2) mixing the solution obtained after a2) with an aqueous or colloidally dispersed solution of a colloid, forming an emulsion, c2) removing the organic solvent from the emulsion and converting the dispersion formed to a dry powder by removing the water and then drying, or a3) converting the vitamin to a liquid by heating above its melting point or dissolving it in an oil or incubating it at room temperature, b3) mixing the melt obtained after a3) with an aqueous or colloidally dispersed solution of a colloid, forming an emulsion, c3) converting the dispersion formed to a dry powder by removing the water and then drying, wherein the effective amount used is 3.5% to 9.5% by weight of propyl gallate based on the total amount of the formulation, where the weight ratio of propyl gallate to vitamin in the production is between 0.21 and 2.63.

34. The process according to claim 32, wherein the propyl gallate is added to the organic solvent-containing vitamin phase and/or to the colloid-containing aqueous solution and/or to the dispersion formed.

35. The process according to claim 32, wherein the process is conducted at a pH of pH 4.5 to pH 8.5.

36. The process according to claim 35, wherein, after addition of the propyl gallate to the colloid-containing aqueous solution, said solution is adjusted to a pH of 6.5 to 8.5.

37. The process according to claim 32, wherein tocopherol is added to the organic solvent-containing vitamin phase.

38. The process according to claim 37, wherein the tocopherol is natural tocopherol.

39. The process according to claim 37, wherein propyl gallate and tocopherol are used in a ratio of 9:1 to 1:2.

40. The process according to claim 32, wherein butylhydroxytoluene is added to the dispersion formed.

41. The process according to claim 40, wherein propyl gallate and butylhydroxytoluene are used in a ratio of 8:1 to 1:4.

42. The process according to claim 32, wherein the vitamin is selected from the group consisting of vitamins D, E, K or Q or derivatives thereof.

43. The process according to claim 32, wherein the colloid is selected from the group consisting of plant gums, modified plant gums, gelatin, modified gelatin, modified starch, lignosulfonate, chitosan, carrageenan, casein, caseinate, whey protein, zein, modified cellulose, pectin, modified pectin, plant proteins and modified plant proteins or mixtures thereof.

44. A pulverulent vitamin formulation produced by a process according to claim 32.

45. An animal feed, food, food supplement, personal care product or pharmaceutical composition comprising the pulverulent vitamin formulation according to claim 24.

Description

EXAMPLES

Example 1 (Example 7 from Table 1)

[0081] 30 g of citranaxanthin were suspended in 240 g of isopropanol together with 1.1 g of ascorbyl palmitate and, with setting of the pressure-limiting valve to 30 bar, mixed continuously with 390 g of isopropanol in a mixing chamber A. At a metering rate of 6 L/h on the suspension side and of 9 L/h on the solvent side, a mixing temperature of 170 C. was established in the mixing chamber A. After a residence time of 0.3 second, the molecularly disperse solution was mixed in mixing chamber B with a solution of 32 g of gelatin, 71.4 g of sucrose and 50 g of glucose syrup in 4000 g of water at a throughput rate of 100 L/h. After the solvent had been removed under reduced pressure in a distillation apparatus, an active ingredient dispersion was obtained, to which 8 g of sunflower oil and 8 g of propyl gallate were added. The propyl gallate was predissolved here in 200 mL of water and adjusted to pH 7 with NaOH. Subsequently, the dispersion was converted to a stable, water-soluble dry powder by spray drying. After dissolution in water, by photon correlation spectroscopy (PCS), a particle size of 386 nm (standard deviation 142.5, polydispersity index PDI 0.185, D(95): 660 nm) was measured (Malvern Zetasizer Nano ZSP).

[0082] Stability Test for Citranaxanthin

[0083] The stability of the particles thus produced was tested in a stress test. For this purpose, specimens each of 100 mg of the particles produced and 4 g of premix mixture were weighed into 50 mL glass bottles. The premix mixture consisted of 50% by weight of fine lime (particle size <1000 m), 20% by weight of wheat bran (particle size <1000 m), 20% by weight of 50% silica-supported choline chloride (particle size <1000 m) and 10% by weight of trace element mixture (particle size 100-500 m), and the trace element mixture of 46.78% by weight of FeSO.sub.4x7H.sub.2O (100-500 m), 37.43% by weight of CuSO.sub.4x5H.sub.2O (100-500 m), 11.79% by weight of ZnO (<500 m), 3.61% by weight of MnO and 0.39% by weight of CoCO.sub.3. After addition of all ingredients, the specimens were carefully mixed by hand. These specimens were stored in a climate-controlled chamber at 40 C. and 70% air humidity for 4 weeks. Prior to commencement of the storage and after completion of the storage, the citranaxanthin content of the specimens was determined. The ratio of the citranaxanthin contents after and prior to storage was used to calculate the retention.

[0084] The retention values of the examples are compiled in the table which follows.

TABLE-US-00001 TABLE 1 Retention Active ingredient Active Antioxidant Site of content after 4- ingredient Antioxidant [% by wt.] antioxidant addition week test [%] 1 Citranaxanthin 0 Dispersion 7.9 2 Citranaxanthin Ethoxyquin 4 added in solid 52.6 form to the dispersion, no pH adjustment 3 Citranaxanthin BHA 4 Molten BHA was 8.2 stirred into the dispersion at 10 000 rpm by Ultraturrax for 2 minutes and this was then introduced 5x via the microfluidizer at 1000 bar 4 Citranaxanthin Na ascorbate 4 added in solid 2.4 form to the dispersion, no pH adjustment 5 Citranaxanthin Methylhydroquinone 4 added in solid 10.2 form to the dispersion, no pH adjustment 6 Citranaxanthin Vitamin E TPGS 4 Added to the 2.2 dispersion as a 10% solution without pH adjustment 7 Citranaxanthin Propyl gallate 4 Dissolved in 47.8 water pH 7 (4% by weight solution) and added to the dispersion 8 Citranaxanthin Lauryl gallate 4 Addition to 15.9 the active ingredient phase, no pH adjustment 9 Citranaxanthin Green tea extract 4 Dissolved 19.4 in water pH 7 and added to the dispersion 10 Citranaxanthin Rosmarinic acid 4 Added to the 14 dispersion as a 10% solution without pH adjustment

[0085] The higher the retention, the better the stability of the particles or preparation thereof.

Example 2

[0086] Effect of pH on Propyl Gallate Activity

[0087] The experiments show that an optimal pH range for the propyl gallate addition is in the range from pH 4.5 up to and including pH 8.5. Even short residence times at pH values greater than 8.5 or predissolution of the propyl gallate at such pH values were sufficient to significantly restrict the activity of propyl gallate.

TABLE-US-00002 TABLE 2a Effect of pH in the propyl gallate-containing dispersion on citranaxanthin stability. Propyl Site of Retention (active gallate propyl constituent after 4 Active [% by gallate pH of sprayed weeks in the test) ingredient wt.] addition dispersion [%] Citranaxanthin 4 Dispersion 4.5 42.2 Citranaxanthin 4 Dispersion 6 39.1 Citranaxanthin 4 Dispersion 7 47.8 Citranaxanthin 4 Dispersion 8 49.4 Citranaxanthin 4 Dispersion 9 28.2 Citranaxanthin 4 Dispersion 10 36.4 Citranaxanthin 4 Dispersion 11 14.7

[0088] This result is also confirmed when the propyl gallate is added not to the vitamin-comprising dispersion, but the propyl gallate is already added to the protective colloid phase (table 2b). A very good result is found when the propyl gallate is added to the protective colloid phase, this is adjusted from a pH of 5 to 7 to a pH of 7 with NaOH, and the pH is raised to 8 to 8.5 with NaOH only 15 to 30 minutes prior to the precipitation.

TABLE-US-00003 TABLE 2b Effect of pH in the propyl gallate-containing protective colloid phase on citranaxanthin stability. Propyl Site of Retention Active gallate propyl ingredient content Active [% by gallate pH of the after 4-week test ingredient wt.] addition colloid phase [%] Citranaxanthin 4 Colloid Preadjustment 44.1 phase to 7; then adjustment to pH 8.5 at maximum Citranaxanthin 4 Colloid 8.5-9.5 13.4 phase

[0089] The mode of addition of the propyl gallate (in solid form or dissolved in water pH 7) to the vitamin-comprising dispersion, by contrast, has no effect on citranaxanthin stability (table 2c).

TABLE-US-00004 TABLE 2c Study of the mode of addition of propyl gallate on retention Propyl Site of Retention Active gallate propyl ingredient content Active [% by gallate Mode of after 4-week test ingredient wt.] addition addition of PG [%] Citranaxanthin 4 Dispersion Dissolved in 47.8 water pH 7 Citranaxanthin 4 Dispersion Dissolved in 46 water pH 7 Citranaxanthin 4 Dispersion Dissolved in 49.4 water pH 7 Citranaxanthin 4 Dispersion Addition in 47.2 solid form without pre- dissolution Citranaxanthin 4 Dispersion Addition in 44.9 solid form without pre- dissolution

Example 3

[0090] Effect of Propyl Gallate Concentration on Active Ingredient Stability

[0091] a). Increasing the propyl gallate concentration increases the stability of the citranaxanthin active ingredient. However, surprisingly, in the case of an increase in the propyl gallate in the formulation to 10% by weight, a significant decline in stability is observed. A very good stabilizing effect was observed at 4% to 9% by weight of propyl gallate in the formulation, preferably 7% to 9% by weight, with an optimum at 8% to 9% by weight (table 3a).

TABLE-US-00005 TABLE 3a Effect of propyl gallate concentration on active ingredient stability of citranaxanthin Propyl Site of propyl Retention Active gallate gallate Active ingredient content ingredient [% by wt.] addition after 4-week test [%] Citranaxanthin 0 Dispersion 7.9 Citranaxanthin 2 Dispersion 20.2 Citranaxanthin 3 Dispersion 26.7 Citranaxanthin 4 Dispersion 47.8 Citranaxanthin 5 Dispersion 45.7 Citranaxanthin 6 Dispersion 45.9 Citranaxanthin 7 Dispersion 49.5 Citranaxanthin 8 Dispersion 55.9 Citranaxanthin 8.5 Dispersion 51.9 Citranaxanthin 9 Dispersion 57.4 Citranaxanthin 10 Dispersion 19.6

[0092] The positive effect of propyl gallate, and also the concentration optimum, can also be confirmed for other carotenoids. (Tables 3b-e).

[0093] b). 30 g of canthaxanthin were suspended in 240 g of isopropanol together with 1.1 g of ascorbyl palmitate and, with setting of the pressure-limiting valve to 30 bar, mixed continuously with 390 g of isopropanol in a mixing chamber A. At a metering rate of 6 L/h on the suspension side and of 9 L/h on the solvent side, a mixing temperature of 170 C. was established in the mixing chamber A. After a residence time of 0.3 second, the molecularly disperse solution was mixed in mixing chamber B with a solution of 32 g of gelatin and 121.4 g of sucrose in 4000 g of water at a throughput rate of 100 L/h. After removal of the solvent under reduced pressure in a distillation apparatus, an active ingredient dispersion was obtained, to which 8 g of sunflower oil and the amounts of propyl gallate specified in table 3b in each case were added. The propyl gallate was predissolved here in 200 mL of water and adjusted to pH 7 with NaOH. Subsequently, the dispersion was converted to a stable, water-soluble dry powder by spray drying. After dissolution in water, by PCS, a particle size of 290 nm (standard deviation 140, polydispersity index PDI 0.193, D(95): 594 nm) was measured (Malvern Zetasizer Nano ZSP).

TABLE-US-00006 TABLE 3b Effect of propyl gallate concentration on active ingredient stability of canthaxanthin Propyl Site of propyl Retention Active gallate gallate Active ingredient content ingredient [%] addition after 4-week premix test [%] Canthaxanthin 4 Dispersion 61.2 Canthaxanthin 6 Dispersion 77.9 Canthaxanthin 8 Dispersion 83.3 Canthaxanthin 9 Dispersion 82.4 Canthaxanthin 10 Dispersion 69.8 Canthaxanthin 12 Dispersion 47.2

[0094] c). 30 g of C30 ester were suspended in 240 g of isopropanol together with 1.1 g of ascorbyl palmitate and, with setting of the pressure-limiting valve to 30 bar, mixed continuously with 390 g of isopropanol in a mixing chamber A. At a metering rate of 6 L/h on the suspension side and of 9 L/h on the solvent side, a mixing temperature of 170C was established in the mixing chamber A. After a residence time of 0.3 second, the molecularly disperse solution was mixed in mixing chamber B with a solution of 32 g of gelatin and 121.4 g of sucrose in 4000 g of water at a throughput rate of 100 L/h. After the solvent had been removed under reduced pressure in a distillation apparatus, an active ingredient dispersion was obtained, to which 8 g of sunflower oil and the amounts of propyl gallate specified in table 3c in each case in % by weight were added. The propyl gallate was predissolved here in 200 mL of water and adjusted to pH 7 with NaOH. Subsequently, the dispersion was converted to a stable, water-soluble dry powder by spray drying. After dissolution in water, by PCS, a particle size of 280 nm (standard deviation 120, polydispersity index PDI 0.181) was measured (Malvern Zetasizer Nano ZSP).

TABLE-US-00007 TABLE 3c Effect of propyl gallate concentration on active ingredient stability of C30 ester Propyl Site of propyl Retention Active gallate gallate Active ingredient content ingredient [% by wt.] addition after 4-week premix test [%] C30 ester 0 Dispersion 6.7 C30 ester 2 Dispersion 13.83 C30 ester 4 Dispersion 42.7 C30 ester 6 Dispersion 57.7 C30 ester 8 Dispersion 64.1 C30 ester 10 Dispersion 58.5 C30 ester 12 Dispersion 54.3

[0095] d). 30 g of -carotene were suspended in 240 g of isopropanol together with 1.1 g of ascorbyl palmitate and, with setting of the pressure-limiting valve to 30 bar, mixed continuously with 390 g of isopropanol in a mixing chamber A. At a metering rate of 6 L/h on the suspension side and of 9 L/h on the solvent side, a mixing temperature of 170 C. was established in the mixing chamber A. After a residence time of 0.3 second, the molecularly disperse solution was mixed in mixing chamber B with a solution of 32 g of gelatin, 71.4 g of sucrose and 50 g of glucose syrup in 4000 g of water at a throughput rate of 100 L/h. After the solvent had been removed under reduced pressure in a distillation apparatus, an active ingredient dispersion was obtained, to which 8 g of sunflower oil and 8 g of propyl gallate were added. The propyl gallate was predissolved here in 200 mL of water and adjusted to pH 7 with NaOH. Subsequently, the dispersion was converted to a stable, water-soluble dry powder by spray drying. After dissolution in water, by PCS, a particle size of 262 nm (standard deviation 182, polydispersity index PDI 0.268) was measured (Malvern Zetasizer Nano ZSP).

TABLE-US-00008 TABLE 3d Comparison of the stabilities of ethoxyquin and propyl gallate on -carotene. Retention Active Site of ingredient Active Antioxidant antioxidant content after 4- ingredient Antioxidant [% by wt.] addition week test [%] -carotene Ethoxyquin 4 Dispersion 22.2 -carotene Propyl gallate 4 Dispersion 30.3

[0096] e). 30 g of C30 ester were suspended in 240 g of isopropanol together with 1.1 g of ascorbyl palmitate and, with setting of the pressure-limiting valve to 30 bar, mixed continuously with 390 g of isopropanol in a mixing chamber A. At a metering rate of 6 L/h on the suspension side and of 9 L/h on the solvent side, a mixing temperature of 170 C. was established in the mixing chamber A. After a residence time of 0.3 second, the molecularly disperse solution was mixed in mixing chamber B with a solution of 32 g of gelatin and 121.4 g of sucrose in 4000 g of water at a throughput rate of 100 L/h. After the solvent had been removed under reduced pressure in a distillation apparatus, an active ingredient dispersion was obtained, to which 8 g of sunflower oil and the amounts of propyl gallate specified in table 3e in each case in % by weight were added. The propyl gallate was predissolved here in 200 mL of water and adjusted to pH 7 with NaOH. Subsequently, the dispersion was converted to a stable, water-soluble dry powder by spray drying. After dissolution in water, by PCS, a particle size of 373 nm (standard deviation 165, polydispersity index PDI 0.203, D(95): 683 nm) was measured (Malvern Zetasizer Nano ZSP).

TABLE-US-00009 TABLE 3e Comparison of the stabilities of ethoxyquin and propyl gallate on C-30 ester. Retention Antiox- Active idant Site of ingredient Active [% by antioxidant content after 4- ingredient Antioxidant wt.] addition week test [%] C30 ester Ethoxyquin 4 Dispersion 28.6 C30 ester Propyl gallate 4 Dispersion 33.4 C30 ester Propyl gallate 4 Dispersion (pH 39.8 adjustment before spraying from pH 8.5 to pH 6.8 with H.sub.2SO.sub.4) C30 ester Propyl gallate 6 Dispersion 44.4 C30 ester Propyl gallate 8 Dispersion 43.4

Example 4

[0097] Effect of Mixed Tocopherol and D,L -Tocopherol on Stabilities

[0098] Owing to their poor water solubility, the tocopherols originating from synthetic and natural sources are dissolved in the phase comprising the active ingredient. If solely natural or synthetic tocopherol is added on its own in each case, there is no difference in their protective effect as antioxidant and in their stabilization of the carotenoids or retinoids.

TABLE-US-00010 TABLE 4a Effect of the synthetic and natural tocopherols on stability Retention Antiox- Active idant Site of ingredient Active [% by antioxidant content after 4- ingredient Antioxidant wt.] addition week test [%] Canthaxanthin Mixed 4 Active 48.7 tocopherol ingredient phase Canthaxanthin D,L- 4 Active 45.7 Tocopherol ingredient phase

[0099] The situation is different when propyl gallate is additionally added as antioxidant to the tocopherols. In this case, the stabilization in the premix test for the combination of mixed tocopherol/propyl gallate is much more marked than for the combination of D,L alpha-tocopherol with propyl gallate (table 4b).

TABLE-US-00011 TABLE 4b Effect of the combination of synthetic or natural tocopherols with propyl gallate on the stabilities of vitamins. Retention Active ingredient Active Antioxidant content after ingredient Antioxidant [% by wt.] 4-week test Canthaxanthin Mixed tocopherol 4 78.1 (in active ingredient phase) + Propyl gallate 4 (in protective colloid phase) Canthaxanthin D,L- Tocopherol 4 57.2 (in active ingredient phase) + Propyl gallate 4 (in protective colloid phase) C30 ester Mixed tocopherol 4 57.5 (in active ingredient phase) + Propyl gallate 4 (in protective colloid phase) C30 ester D,L- Tocopherol 4 29.2 (in active ingredient phase) + Propyl gallate 4 (in protective colloid phase) Citranaxanthin Mixed tocopherol 4 67.5 (in active ingredient phase) + Propyl gallate 4 (in protective colloid phase) Citranaxanthin D,L- Tocopherol 4 21.3 (in active ingredient phase) + Propyl gallate 4 (in protective colloid phase)

Example 5

[0100] a). Synergistic Effect Between Propyl Gallate and Tocopherol

[0101] For the combination of propyl gallate with tocopherol, it has been found that, for this system, the total concentration of antioxidant in the formulation can be reduced without losing stability. If the stabilities for the formulation comprising 4% propyl gallate (61.2%) and that comprising 4% mixed tocopherol (48.7%) are compared with one another, for this system, the propyl gallate is clearly the better antioxidant. If, by contrast, 4% propyl gallate is mixed with 4% mixed tocopherol and the stability thereof (80.3%) is compared with that comprising 8% propyl gallate (83.3%), a synergistic effect that would not have been expected from the individual values is apparent. This becomes even more noticeable when, with constant propyl gallate content, the concentration of mixed tocopherol is reduced from 4% to 2%. For this system, a stability of 80.6% is measured, whereas, for a system comprising 6% propyl gallate, only a stability of 71.3% is obtained. This shows dearly that only a particular concentration of mixed tocopherol is required to obtain a significant rise in stability with reduced antioxidant content in the formulation.

TABLE-US-00012 TABLE 5a Combination of mixed tocopherol with propyl gallate. Retention Canthaxanthin Mixed after 4- Active Propyl gallate tocopherol week test ingredient [% by wt.] [% by wt.] [%] Canthaxanthin 4 0 61.2 Canthaxanthin 6 0 71.3 Canthaxanthin 8 0 83.3 Canthaxanthin 0 4 48.7 Canthaxanthin 4 4 80.3 Canthaxanthin 4 2 80.8

[0102] 2% by weight of mixed tocopherol in combination with 4% by weight of propyl gallate almost reaches the stability value for 4% by weight of mixed tocopherol in combination with 4% by weight of propyl gallate. If, however, the proportion of mixed tocopherol is reduced to 1% by weight, again in combination with 4% by weight of propyl gallate, the stability values begin to fall (table 5b).

TABLE-US-00013 TABLE 5b Combination of mixed tocopherol with propyl gallate. Retention Canthaxanthin Mixed after 4- Active Propyl gallate tocopherol week test ingredient [% by wt.] [% by wt.] [%] Canthaxanthin 4 (in protective 2 (in active 76 colloid phase pH 7) ingredient phase) Canthaxanthin 4 (in protective 4 (in active 80.6 colloid phase pH 7) ingredient phase) Canthaxanthin 4 (in protective 1 (in active 72.8 colloid phase pH 7) ingredient phase)

TABLE-US-00014 TABLE 5c Combination of mixed tocopherol with propyl gallate Retention Canthaxanthin Mixed after 4- Active Propyl gallate tocopherol week test ingredient [% by wt.] [% by wt.] [%] C30 ester 4 0 42.7 C30 ester 0 4 11 C30 ester 4 4 61.7 Citranaxanthin 4 0 39.1 Citranaxanthin 0 4 10.8 Citranaxanthin 4 4 66.5

[0103] Experimental Method for the Addition of 4% by Weight of Propyl Gallate and 4% by Weight of Tocopherol

[0104] 30 g of citranaxanthin were suspended in 240 g of isopropanol together with 1.1 g of ascorbyl palmitate and 9 g of mixed tocopherol and, with setting of the pressure-limiting valve to 30 bar, mixed continuously with 390 g of isopropanol in a mixing chamber A. At a metering rate of 6 L/h on the suspension side and of 9 L/h on the solvent side, a mixing temperature of 170C was established in the mixing chamber A. After a residence time of 0.3 second, the molecularly disperse solution was mixed in mixing chamber B with a solution, adjusted to pH 9, of 32 g of gelatin, 71.4 g of sucrose, 50 g of glucose syrup and 9 g of propyl gallate in 4100 g of water at a throughput rate of 100 L/h. After the solvent had been removed under reduced pressure in a distillation apparatus, an active ingredient dispersion was obtained, to which 9 g of sunflower oil were added. Subsequently, the dispersion was converted to a stable, water-soluble dry powder by spray drying. After dissolution in water, by PCS, a particle size of 280 nm (standard deviation 142.5, polydispersity index PDI 0.185) was measured (Malvern Zetasizer Nano ZSP).

[0105] b). Synergistic Effect Between Propyl Gallate and BHT

TABLE-US-00015 TABLE 5d Combination of BHT with propyl gallate. Retention Citranaxanthin after 4- Active Propyl gallate BHT week test ingredient [% by wt.] [% by wt.] [%] Citranaxanthin 4 0 61.2 Citranaxanthin 4 4 82.3 Citranaxanthin 0 4 56.1 Citranaxanthin 0 4 65.5 Citranaxanthin 0 4 67.9 Citranaxanthin 4% by wt. of ethoxyquin 79.3

[0106] Experimental Method for the Addition of 4% by Weight of Propyl Gallate and 4% by Weight of Butylhydroxytoluene

[0107] 30 g of citranaxanthin are suspended in 240 g of isopropanol together with 1.1 g of ascorbyl palmitate and, with setting of the pressure-limiting valve to 30 bar, mixed continuously with 390 g of isopropanol in a mixing chamber A. At a metering rate of 6 L/h on the suspension side and of 9 L/h on the solvent side, a mixing temperature of 170 C. is established in the mixing chamber A. After a residence time of 0.3 second, the molecularly disperse solution is mixed in mixing chamber B with a solution, adjusted to pH 9, of 32 g of gelatin, 71.4 g of sucrose, 50 g of glucose syrup and 9 g of propyl gallate in 4100 g of water at a throughput rate of 100 L/h. After the solvent has been removed under reduced pressure in a distillation apparatus, an active ingredient dispersion is obtained, to which 9 g of sunflower oil and 9 g of BHT dissolved therein are added.

[0108] Subsequently, the dispersion was converted to a stable, water-soluble dry powder by spray drying. After dissolution in water, by PCS, a particle size of 290 nm (standard deviation 140, polydispersity index PDI 0.180) was measured (Malvern Zetasizer Nano ZSP).