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EP-4739282-A1 - SOLID PREPARATIONS OF BETA-CAROTENE

EP4739282A1EP 4739282 A1EP4739282 A1EP 4739282A1EP-4739282-A1

Abstract

The present invention relates to solid preparations of β-carotene in the form of beadlets, comprising a) a beadlet core containing a.1 20 to 40%, by weight of β-carotene as a component a.1; a.2 30 to 75% by weight of isomalt as a component a.2; a.3 5 to 55% by weight of at least one protective colloid from the group of polysaccharides and modified polysaccharides as a component a.3, where the relative amount of each component refers to the total dry weight of beadlet core, and b) optionally a coating. The present invention also relates to solid oral dosage form containing a solid preparation as described herein and one or more excipients.

Inventors

  • HIRSCHBERG, Cosima
  • FELDTHUSEN JENSEN, JESPER
  • WIEBE, Julia
  • KOEPSEL, CHRISTIAN

Assignees

  • BASF SE

Dates

Publication Date
20260513
Application Date
20240703

Claims (15)

  1. 1. A solid preparation of p-carotene in the form of beadlets, comprising a) a beadlet core containing a.1 20 to 40%, by weight of p-carotene as a component a.1 ; a.2 30 to 75% by weight of isomalt as a component a.2; a.3 5 to 55% by weight of at least one protective colloid from the group of polysaccharides and modified polysaccharides as a component a.3, where the relative amount of each component refers to the total dry weight of beadlet core, and b) optionally a coating.
  2. 2. The solid preparation according to claim 1, where the beadlet core contains. a.1 20 to 35% by weight, in particular 25 to 30% by weight of p-carotene as a component a.1 ; a.2 40 to 60% by weight, in particular 40 to 50% by weight of isomalt as a component a.2; a.3 10 to 35% by weight, in particular 15 to 35% by weight of at least one protective colloid from the group of polysaccharides and modified polysaccharides as a component a.3.
  3. 3. The solid preparation according to any one of the preceding claims, wherein the weight ratio of isomalt to the component a.3 is in the range of 1.4: 1 to 3.0: 1 , in particular in the range of 1.45:1 to 2.5:1 , especially in the range of 1:48:1 to 2.2:1.
  4. 4. The solid preparation according to any one of the preceding claims, wherein the component a.3 is selected from modified starches and gums, such as acacia gum.
  5. 5. The solid preparation according to claim 4, wherein the modified starches are selected from alkyl succinate modified starch and alkenyl succinate modified starch.
  6. 6. The solid preparation according to claim 5, wherein the alkyl succinate modified starch and alkenyl succinate have a weight average molecular weight in the range of 5,000 to 1 ,000,000 g/mol as determined by gel permeation chromatography and/or a degree of substitution in the range of 1 to 3% with respect to the glucose units of the starch.
  7. 7. The solid preparation according to any one of the preceding claims, wherein the beadlets have a medium diameter in the range of 50 to 1000 pm, in particular in the range of 100 to 500 pm, especially in the range of 180-350 pm, as determined by sieving according to European Pharmacopeia (Ph. Eur.).
  8. 8. The solid preparation according to any one of the preceding claims, wherein the coating is essentially formed by one or more coating agents selected from powdering agents, anticaking agents, flow aids and combinations thereof.
  9. 9. The solid preparation according to claim 8, wherein the coating agent is selected from native starches, earth alkali phosphate, silica based flow aids earth alkali carbonates and combinations thereof.
  10. 10. The solid preparation according to any one of the preceding claims, wherein the total amount of the coating agent is in the range of 5 to 30% by weight, in particular 8 to 25% by weight, based on the dry weight of the beadlet.
  11. 11. A solid oral dosage form containing a solid preparation according to any one of the preceding claims and one or more excipients.
  12. 12. The solid oral dosage form of claim 11 which is a tablet obtained by compaction of a mixture of the solid preparation and the one or more excipients.
  13. 13. The solid oral dosage form of claim 12 which is a tablet, in particular a multivitamin mineral tablet.
  14. 14. The use of isomalt in the solid preparation of p-carotene as defined in any one of claims 1 to 10 for increasing the chemical stability of p-carotene in said the solid preparation and/or in solid dosage forms containing said solid preparation.
  15. 15. The use according to claim 14, wherein said solid composition has been compacted to multivitamin mineral tablets having a p-carotene retention over time (timespan months, 40°C, 75 RH (relative humidity) of 80% or more after 3 months.

Description

SOLID PREPARATIONS OF BETA-CAROTENE The present invention relates to solid preparations of p-carotene in the form of beadlets which contain a high amount of p-carotene. P-Carotene is an organic, strongly colored red-orange pigment. Dietary p-carotene is a provitamin A compound, converting in the body to retinol (vitamin A). p-Carotene is frequently used as a vitamin A source in vitamin supplements and for coloring food. B-Carotene is insoluble in water and its solubility in fats and oils is found to be only low, as well. This limited solubility and the great sensitivity of B-carotene to oxidation stand in the way of direct use of the relatively coarse particle products obtained by chemical synthesis. Moreover, the bioavailability of coarse-particle B-carotene is quite poor and not suitable for the use in vitamin supplements. Apart from that, coarse particle B-carotene provide only poor coloring results. These problems can in principle be overcome by solid powder preparations in which the B-carotene is present in finely divided form and the fine particles of B-carotene are embedded in a solid matrix containing one or more water-soluble carbohydrates and/or protective colloids as main matrix components and are thus protected against degradation. Beadlets are a special form of powder preparations. They have typically a core which contains an active, e. g. B-carotene and matrix materials and optionally a covering or coating, which reduces the sticking of the particles. Beadlets are usually obtained by providing a dispersion of the respective active, here B-carotene, in water and/or a volatile organic solvent, grinding it to the desired particle size if necessary and then spray-drying suspension together with the matrix material. Beadlets have typically a medium particle size (d50) in the range of 50 pm to 1000 pm, in particular 100 to 500 pm as determined by sieving according to European Pharmacopeia (Ph. Eur.). WO 2006/032399 describes dry powders of carotenoids, such as B-carotene, which contain a combination of isomalt and a protective colloid as a matrix material. The powders of WO 2006/032399 provide an improved stability to the B-carotene against degradation, in particular oxidative degradation, when the powder is formulated in a solid dosage form, such as a tablet, in comparison to powders wherein the isomalt was replaced by another carbohydrate, such as sucrose, or by a sugar alcohol, such as mannitol. However, the stabilization of B-carotene provided by the powders of WO 2006/032399 in solid dosage forms, in particular in solid dosage forms obtained by compacting mixture of the powder with one or more excipients such as tablets, is not entirely satisfactory. In particular, when the powder is incorporated into a solid dosage form, in particular into solid dosage forms obtained by compacting mixture of the powder with one or more excipients such as tablets. The stability problem becomes even more prominent, when the content of the B-carotene in the beadlet core is higher than 15% by weight, in particular at least 20% by weight. It was surprisingly found that the stability of B-carotene in solid dosage forms such as tablets can be further improved by providing beadlets containing a combination of isomalt and at least one protective colloid from the group of polysaccharides and modified polysaccharides with balanced relative amounts of isomalt and the at least one protective colloid. In particular, it was found that a high isomalt content of 30 to 75% by weight, in particular 40 to 60% by weight, especially 40 to 50% protects the encapsulated betacarotene to a higher degree than a higher content of protective colloid. Therefore, the present invention relates to solid preparations of p-carotene in the form of beadlets, comprising a) a beadlet core, which contains a.1) 20 to 40% by weight, in particular 20 to 35% by weight, especially 25 to 30% by weight of p-carotene as a component a.1 ; a.2) 30 to 75% by weight, in particular 40 to 60% by weight, especially 40 to 50% by weight of isomalt as a component a.2; a.3) 5 to 50% by weight, in particular 10 to 35% by weight, especially 25 to 35% by weight of at least one protective colloid from the group of polysaccharides and modified polysaccharides as a component a.3, where the relative amount of each component refers to the total dry weight of beadlet core, and optionally b) a beadlet coating. The solid preparations of the present invention provide superior stability to B-carotene, in particular, when the solid preparations are used in solid dosage forms, especially in solid dosage forms which are obtained by compaction of the solid preparation in mixture with one or more excipients. The solid dosage forms can be easily prepared by well-known techniques for preparing beadlet formulations and are easily to handle. Therefore, a further aspect of the present invention relates to solid oral dosage forms containing a solid preparation according to present inventio