Composition for controlled release of physiologically active substances and process for its preparation

1. A rumen-resistant composition in the form of microgranules, each microgranule containing:

i) a core comprising:

a) one or more physiologically active substances selected from the group consisting of amino acids, vitamins, enzymes, proteins, carbohydrates, probiotic microorganisms, prebiotic foods, mineral salts, choline derivatives of choline and organic acids;

b) a matrix comprising substances selected from the group consisting of binding substances, inert substances and extrusion adjuvants; and

c) a disintegrant agent selected from the group consisting of amides in dry form, vegetal lecithins, ethoxylated oils, monoglycerides, diglycerides of fatty acids, agar agar in dry form, effervescent mixtures of bicarbonate of an alkali metal and a polycarboxylic acid, effervescent mixtures of bicarbonate of ammonium and a polycarboxylic acid, cellulose in dry form, and methacrylate copolymers; and

ii) at least two coating layers of the core, each having a different composition;

wherein a first coating layer proximal to the core comprises (i) a hydrophobic substance selected from the group consisting of: fats, hydrogenated oils, monoglycerides of fatty acids, diglycerides of fatty acids, fatty acid esters, and fatty acid alcohols, and (ii) at least one pollutant substance selected from the group of emulsifying substances, fatty acids, and methacrylate copolymers;

wherein a second coating layer, arranged on the outside of the first layer, comprises (i) at least one pollutant substance selected from the group of emulsifying substances, fatty acids, and methacrylate copolymers, and (ii) a hydrophobic substance selected from the group consisting of microcrystalline waxes, paraffin waxes, vegetal waxes and edible synthetic waxes.

2. The composition according to claim 1 , wherein said emulsifying substance is selected from the group consisting of soy lecithin, sunflower lecithin, ethoxylated castor oil, alkaline metal alginates, magnesium alginates, and a combination thereof.

3. The composition according to claim 1 , wherein said polluting fatty acid is selected from the group consisting of palmitic acid, oleic acid, linoleic acid, linolenic acid, stearic acid, and a combination thereof.

4. The composition according to claim 1 , wherein said methacrylate copolymer is polymethyl methacrylate (PMMA).

5. The composition according to claim 1 , wherein said microgranule comprises at least two coating layers; and each coating layer comprises an amount of polluting substance between 0.01% and 40% by weight with respect to the weight of the coating layer.

6. The composition according to claim 5 , wherein each coating layer comprises an amount of emulsifying substance between 0.1% and 6% by weight with respect to the weight of the coating layer.

7. The composition according to claim 5 , wherein each coating layer comprises an amount of polluting fatty acid between 10% and 35%.

8. The composition according to claim 1 , wherein one or each coating layer comprises palmitic acid, oleic acid, linoleic acid, linolenic acid, stearic acid or a combination thereof.

9. The composition according to claim 1 , wherein one or each coating layer comprises soy or sunflower lecithin.

10. The composition according to claim 1 , wherein one or each coating layer comprises ethoxylated castor oil.

11. The composition according to claim 1 , wherein one or each coating layer comprises sodium or magnesium alginate.

12. The composition according to claim 1 , wherein one or each coating layer comprises polymethyl methacrylate (PMMA).

13. The composition according to claim 1 , wherein the two coating layers comprise different amounts of pollutants.

14. The composition according to claim 1 , wherein said two coating layers comprise different amounts of emulsifying substances, fatty acids, or methacrylate copolymers.

15. The composition according to claim 1 ,

wherein the first coating layer comprises (i) one or more hydrogenated vegetable oil in an amount that is about 50% to about 90% by weight with respect to the weight of the first coating layer, and (ii) a fatty acid and/or an emulsifying agent in an amount that is about 5% to about 50% by weight with respect to the weight of the second coating layer.

16. The composition according to claim 1 , wherein in each microgranule the total weight of the coating layers is between 10% and 50% of the microgranule weight.

17. The composition according to claim 1 , wherein said core comprises a disintegrant agent in an amount by weight between 1.5% and 6.5%.

18. The composition according to claim 1 , wherein said core has a cylindrical shape, the height of which is comprised between 0.5 mm and 2 mm or a spheroidal shape, the diameter of which is comprised between 0.5 mm and 2 mm.

19. A premixture for animal feedstuff comprising the composition according claim 1 .

20. A feedstuff comprising the premixture according to claim 19 .

21. A process for the preparation of a composition according to claim 1 , comprising the steps of:

obtaining microgranules by extruding a mixture comprising:

a) one or more physiologically active substances selected from the group consisting of amino acids, vitamins, enzymes, proteins, carbohydrates, probiotic microorganisms, prebiotic foods, mineral salts, choline derivatives of choline and organic acids;

b) one or more matrix substances selected from the group consisting of binding substances, inert substances, and extrusion adjuvants; and

c) a disintegrant agent selected from the group consisting of amides in dry form, vegetal lecithins, ethoxylated oils, monoglycerides, diglycerides of fatty acids, agar agar in dry form, effervescent mixtures of bicarbonate of an alkali metal and a polycarboxylic acid, effervescent mixtures of bicarbonate of ammonium and a polycarboxylic acid, cellulose in dry form, and methacrylate copolymers;

optionally subjecting the microgranule to spheronization;

forming at least two coating layers on the microgranules, each having a different composition,

wherein a first coating layer proximal to the microgranule comprises (i) a hydrophobic substance selected from the group consisting of: fats, hydrogenated oils, monoglycerides of fatty acids, diglycerides of fatty acids, fatty acid esters, and fatty acid alcohols, and (ii) at least one pollutant substance selected from the group of emulsifying substances, fatty acids, and methacrylate copolymers;

wherein a second coating layer, arranged on the outside of the first layer, comprises (i) at least one pollutant substance selected from the group of emulsifying substances, fatty acids, and methacrylate copolymers, and (ii) a hydrophobic substance selected from the group consisting of microcrystalline waxes, paraffin waxes, vegetal waxes and edible synthetic waxes.