VITAMIN FORMULATION

Abstract

The present patent application relates to solid particles comprising at least one fatsoluble vitamin, which are more stable when compressed into tablets.

Claims

1. Solid particles comprising (i) at least 20 wt-%, based on the total weight of the solid particles, of least one fat soluble vitamin, (ii) at least one emulsifier, and (iii) at least one non-reducing sugar.

2. Solid particles according to claim 1 comprising 5-55 weight-% (wt-%), based on the total weight of the solid particle, of at least one non-reducing sugar (preferably trehalose).

3. Solid particles according to claim 1 comprising 10-50 weight-% (wt-%), based on the total weight of the solid particle, of at least one non-reducing sugar.

4. Solid particles according to claim 1, wherein the fat soluble vitamin is chosen from the group of vitamin A and its derivatives (such as vitamin A acetate or vitamin A palmitate).

5. Solid particles according to claim 1 comprising 20-75 wt-%, based on the total weight of the solid particle, of at least one fat-soluble vitamin.

6. Solid particles according to claim 1 comprising 25-70 wt-%, based on the total weight of the solid particle, of at least one fat-soluble vitamin.

7. Solid particles according to claim 1 comprising 20-70 wt-%, based on the total weight of the solid particles, of at least one emulsifier.

8. Solid particles according to claim 1, wherein the at least emulsifier is chosen from the group consisting of modified (food) starches, ascorbyl palmitate, pectin, alginate, carrageenan, furcellaran, dextrin derivatives, celluloses and cellulose derivatives (e.g. cellulose acetate, methyl cellulose, hydroxypropyl methyl cellulose), lignosulfonate, polysaccharide gums (such as gum acacia (=gum arabic), modified gum acacia, TIC gum, flaxseed gum, ghatti gum, tamarind gum and arabinogalactan), gelatine (bovine, fish, pork, poultry), plant proteins (such as are for example peas, soybeans, castor beans, cotton, potatoes, sweet potatoes, manioc, rapeseed, sunflowers, sesame, linseed, safflower, lentils, nuts, wheat, rice, maize, barley, rye, oats, lupin and sorghum), animal proteins including milk or whey proteins, lecithin, polyglycerol ester of fatty acids, monoglycerides of fatty acids, diglycerides of fatty acids, sorbitan ester, and sugar ester (as well as derivatives thereof).

9. Use of the solid particles according to claim 1 in the production of compressed tablets.

10. Compressed tablets comprising at least one solid particle according to claim 1.

Description

EXAMPLES

Example 1: Food Modified Starch and Trehalose

[0069] 370.6 g of deionized water were heated up to 60 C.-65 C. in a vessel. 316.75 g of food modified starch and 121.2 g of trehalose were added and the mixture was brought into solution while stirring at 60-65 C. The obtained solution was cooled to 50-55 C. and degassed for 1 hour. Thereupon, 190.82 g of an oil mixture (180.78 g vitamin A acetate, 5.02 g BHT and 5.02 g dl-alpha-tocopherol) were added to the matrix system and emulsified. The temperature of the process was always kept below 65 C. After emulsification the inner phase of the emulsion had an average particle size of about 272 nm (Dv(0.1)=100 nm, Dv(0.5)=272 nm, Dv(0.9)=559 nm), measurement realized by laser diffraction (Malvern 3000). After emulsification the moisture of the emulsion, determined by a halogen moisture analyzer (Mettler Toledo, Type HR73-P), was checked and adapted if necessary. Afterwards 150 g of the emulsion were sprayed into a spray pan containing 1500 g of corn starch using a rotating spray nozzle. The obtained particles were sieved off (150 to 600 m) from the excess of corn starch and dried at room temperature using a stream off air. The final product particle size after drying was in average 246 m (Dv(0.1)=198 m, Dv(0.5)=246 m, Dv(0.9)=303 m) measured by laser diffraction (Malvern 3000). Solid particles with the composition as listed in table 1 have been obtained.

TABLE-US-00001 TABLE 1 Composition [wt %] Vit. A Ac. 2.8 Mio I.U/g 27.00 dl-alpha-Tocopherol 0.75 BHT 0.75 Food modified starch 47.31 Trehalose 18.19 Corn Starch 4.00 Water 2.00 Total 100.00

Example: 2 Food Modified Starch and Trehalose

[0070] 381 g of deionized water were heated up to 60 C.-65 C. in a vessel. 316.75 g of food modified starch and 122.2 g of trehalose were added and the mixture was brought into solution while stirring at 60-65 C. The obtained solution was cooled to 50-55 C. and degassed for 1 hour. Thereupon, 190.78 g of vitamin A acetate were added to the matrix system and emulsified. The temperature of the process was always kept below 65 C. After emulsification the inner phase of the emulsion had an average particle size of about 333 nm (Dv(0.1)=175 nm, Dv(0.5)=333 nm, Dv(0.9)=558 nm), measurement realized by laser diffraction (Malvern 3000). After emulsification the moisture of the emulsion, determined by a halogen moisture analyzer (Mettler Toledo, Type HR73-P), was checked and adapted if necessary. Afterwards 150 g of the emulsion were sprayed into a spray pan containing 1500 g of corn starch using a rotating spray nozzle. The obtained particles were sieved off (150 to 600 m) from the excess of corn starch and dried at room temperature using a stream off air. The final product particle size after drying was in average 180 m (Dv(0.1)=180 m, Dv(0.5)=240 m, Dv(0.9)=321 m) measured by laser diffraction (Malvern 3000).

[0071] Solid particles with the composition as listed in table 21 have been obtained.

TABLE-US-00002 TABLE 2 Composition [wt %] Vit. A Ac. 2.8 Mio I.U/g 27.00 Food modified starch 48.31 Trehalose 18.19 Corn Starch 4.00 Water 2.00 Total 100.00

Example 3: Food Modified Starch and Sucrose

[0072] 370.6 g of deionized water were heated up to 60 C.-65 C. in a vessel. 317.4 g of food modified starch and 122.1 g of sucrose were added and the mixture was brought into solution while stirring at 60-65 C. The obtained solution was cooled to 50-55 C. and degassed for 1 hour. Thereupon, 197.3 g of an oil mixture (186.9 g vitamin A acetate, 10.4 g BHT) were added to the matrix system and emulsified. The temperature of the process was always kept below 65 C. After emulsification the inner phase of the emulsion had an average particle size of about 276 nm (Dv(0.1)=112 nm, Dv(0.5)=276 nm, Dv(0.9)=516 nm), measurement realized by laser diffraction (Malvern 3000). After emulsification the moisture of the emulsion, determined by a halogen moisture analyzer (Mettler Toledo, Type HR73-P), was checked and adapted if necessary. Afterwards 150 g of the emulsion were sprayed into a spray pan containing 1500 g of corn starch using a rotating spray nozzle. The obtained particles were sieved off (150 to 600 m) from the excess of corn starch and dried at room temperature using a stream off air. The final product particle size after drying was in average 272 m (Dv(0.1)=197 m, Dv(0.5)=272 m, Dv(0.9)=377 m) measured by laser diffraction (Malvern 3000).

[0073] Solid particles with the composition as listed in Table 3 have been obtained

TABLE-US-00003 TABLE 3 Composition [wt %] Vit. A Ac. 2.8 Mio I.U/g 27.00 BHT 1.50 Food modified starch 45.86 Sucrose 17.64 Corn Starch 5.00 Water 3.00 Total 100.00

Example 4: Gum Acacia and Trehalose

[0074] 381 g of deionized water were heated up to 60 C.-65 C. in a vessel. 143.78 g of food modified starch and 287.56 g of trehalose were added and the mixture was brought into solution while stirring at 60-65 C. The obtained solution was cooled to 50-55 C. and degassed for 1 hour. Thereupon, 187.68 g of an oil mixture (177.80 g vitamin A acetate, 4.94 g BHT and 4.94 g dl-alpha-tocopherol) were added to the matrix system and emulsified. The temperature of the process was always kept below 65 C. After emulsification the inner phase of the emulsion had an average particle size of about 493 nm (Dv(0.1)=215 nm, Dv(0.5)=493 nm, Dv(0.9)=987 nm), measurement realized by laser diffraction (Malvern 3000). After emulsification the moisture of the emulsion, determined by a halogen moisture analyzer (Mettler Toledo, Type HR73-P), was checked and adapted if necessary. Afterwards 150 g of the emulsion were sprayed into a spray pan containing 1500 g of cornstarch using a rotating spray nozzle. The obtained particles were sieved off (150 to 600 m) from the excess of corn starch and dried at room temperature using a stream off air. The final product particle size after drying was in average 234 m (Dv(0.1)=189 m, Dv(0.5)=234 m, Dv(0.9)=293 m) measured by laser diffraction (Malvern 3000).

[0075] Solid particles with the composition as listed in Table 4 have been obtained.

TABLE-US-00004 TABLE 4 Composition [wt %] Vit. A Ac. 2.8 Mio I.U/g 27.00 dl-alpha-Tocopherol 0.75 BHT 0.75 Gum acacia 21.83 Trehalose 43.67 Corn Starch 4.00 Water 2.00 Total 100.00

Example 5: Stability in Stress Tablets

[0076] 100 g of powder consisting of 27 g of vitamin A acetate particles (as obtained in Example 1), 33.24 g microcrystalline cellulose, 49.86 g calcium phosphate and 0.2 g of magnesium stearate was mixed during 10 min. This end preparation was then compressed with a pressure of 35 KN. The tablets (common disk-shaped; 0.2 g) were stored at room temperature in a closed brown-glass bottle and the vitamin A acetate content determined after 1, 7 and 35 days of storage.

[0077] For the purpose to show the superior property of the particles according to the present invention, comparative examples were also carried, wherein instead of trehalose or sucrose other sugars, which are no non-reducing sugars, have been used. These comparative solid particles were prepare as described in Example 1.

[0078] The impact of the use of trehalose is far better than other types of plasticizer. This can be seen on the FIGS. 1, 2, and 3. (in tables 5-7, the solid particles are listed. The concentration of the ingredients is the same as in Example 1).

TABLE-US-00005 TABLE 5 Compressed tablets as on FIG. 1: Graph Composition of the solid particles 1 Vitamin A acetate Food Maltodextrin12 BHT/toco modified starch 2 Vitamin A acetate Food trehalose BHT/toco modified starch 3 Vitamin A acetate Food sucrose BHT/toco modified starch

TABLE-US-00006 TABLE 6 Compressed tablets as on FIG. 2: Graph Composition of the solid particles 1 Vitamin A acetate Food Maltodextrin BHT/toco modified starches 20-23 2 Vitamin A acetate Food Maltodextrin BHT/toco modified starches 12 3 Vitamin A acetate Food trehalose BHT/toco modified starch

TABLE-US-00007 TABLE 7 Compressed tablets as on FIG. 3: Graph Composition of the solid particles 1 Vitamin A acetate Gum acacia Maltodextrin BHT/toco 20-23 2 Vitamin A acetate Gum acacia Maltodextrin BHT/toco 12 3 Vitamin A acetate Gum acacia trehalose BHT/toco