PHARMACEUTICAL OR NUTRACEUTICAL COMPOSITION WITH SUSTAINED RELEASE CHARACTERISTIC AND WITH RESISTANCE AGAINST THE INFLUENCE OF ETHANOL

• US 20150190348A1
• Filed: 10/18/2012
• Published: 07/09/2015
• Est. Priority Date: 08/27/2012
• Status: Active Grant

• Current Assignee: Evonik Operations GmbH (Rag-Stiftung)
• Original Assignee: Evonik Industries AG (Rag-Stiftung)
• Inventors: Shah, Harsh, Patil, Preeti, Shetty, Smitha, Haksar, Priyanka Bansilal, Joshi, Shraddha Sanjeev
• Granted Patent: US 10,842,752 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/2826 Sugars or sugar alcohols, e.g. sucrose; Derivatives thereof
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/286 Polysaccharides, e.g. gums; Cyclodextrin
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5036 Polysaccharides, e.g. gums, alginate; Cyclodextrin
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings

Abstract

A pharmaceutical or nutraceutical composition with a core, an inner coating layer, and an outercoating layer, wherein a pharmaceutical or a nutraceutical active ingredient is contained in the core, one or more salts of alginic acid is contained in the inner coating layer, and one or more water-insoluble polymers or copolymers is contained in the outer coating layer. In the composition, the ratio of the amount of the one or more salts of alginic acid in the inner coating layer is at least 2.5:1 by weight to the amount of the one or more water-insoluble polymers or copolymers in the outer coating layer.

Claims

1. A pharmaceutical or nutraceutical composition, comprising

a) a core, comprising a pharmaceutical or a nutraceutical active ingredient

b) an inner coating layer comprising a salt of alginic acid and

c) an outer coating layer comprising a water-insoluble polymers polymer or copolymers copolymer,

wherein the ratio by weight of the amount of the salt of alginic acid in the inner coating layer to the amount of the water-insoluble polymer or copolymer in the outer coating layer is at least 2.5:

1.

2. The pharmaceutical or nutraceutical composition according to claim 1, wherein the total amount of the inner coating layer is in the range of 10 to 100% by weight in relation to the weight of the core.

3. The pharmaceutical or nutraceutical composition according to claim 1, wherein, except for the inner coating layer and the outer coating layer, no further controlling layers are present which control the release the pharmaceutical or a nutraceutical active ingredient.

4. The pharmaceutical or nutraceutical composition according to claim 1, wherein the salt of alginic acid in the inner coating layer have has a viscosity of 30 to 720 cP of a 1% aqueous solution based on weight/weight.

5. The pharmaceutical or nutraceutical composition according to claim 1, wherein the inner coating layer comprises up to 70% by weight of a pharmaceutical or nutraceutically acceptable excipient.

6. The pharmaceutical or nutraceutical composition according to claim 1, wherein the release of the pharmaceutical or nutraceutical active ingredient, in % under in-vitro conditions at pH 1.2 for 2 hours in simulated gastric fluid according to USP and subsequent buffer pH 6.8 without the addition of ethanol, does not differ by more than plus/minus 20% as an absolute percentage in the same media with the addition of 40% v/v ethanol.

7. The pharmaceutical or nutraceutical composition according to claim 1, wherein the release, in % of the pharmaceutical or nutraceutical active ingredient under in-vitro conditions at pH 1.2 for 2 hours in simulated gastric fluid according to USP and subsequent buffer pH 6.8 without the addition of calcium ions, does not differ by more than plus/minus 20% as an absolute percentage in the same media with the addition of 1.25 mM calcium ions.

8. The pharmaceutical or nutraceutical composition according to claim 1, wherein the release of the pharmaceutical or nutraceutical active ingredient under in-vitro conditions after 2 hours at pH 1.2 in simulated gastric fluid and subsequent change of the medium to buffered medium of pH 6.8 according to USP is 30 to 100% in a total time from 4 to 16 hours.

9. The pharmaceutical or nutraceutical composition according to claim 1, wherein the core or the inner coating layer or the outer coating layer comprise at least one pharmaceutical or nutraceutically acceptable excipients selected from the group consisting of an antioxidant, a brightener, a binding agent, a flavoring agent, a flow aid, a fragrance, a glidant, a penetration-promoting agent, a pigment, a plasticizer, a polymer, different from the salt of alginic acid and different from the water-insoluble polymer or a cellulosic polymer, a pore-forming agent and a stabilizer.

10. The pharmaceutical or nutraceutical composition according to claim 1, wherein the water-insoluble polymer belongs to the group of (meth)acrylate copolymers.

11. The pharmaceutical or nutraceutical composition according to claim 1, wherein the water-insoluble copolymer is a copolymer comprising free-radical polymerized units of more than 95 up to 100% by weight C₁- to C₄-alkyl esters of acrylic or of methacrylic acid and less than 5% by weight of acrylic or methacrylic acid.

12. The pharmaceutical or nutraceutical composition according to claim 1, wherein the water-insoluble polymer belongs to the group of vinyl polymers or copolymers or to the group of water-insoluble celluloses.

13. The pharmaceutical or nutraceutical composition according to claim 1, wherein the pharmaceutical or nutraceutical composition is gastric resistant and is a coated tablet, a coated minitablet, a coated pellet, a coated granule, a sachet, a capsule filled with coated pellets or with powder or with granules, or a coated capsule.

14. A process for producing the pharmaceutical or nutraceutical composition according to claim 1, comprising

forming the core comprising the active ingredient by direct compression, compression of dry, wet or sintered granules, by extrusion and subsequent rounding off, by wet or dry granulation, by direct pelleting or by binding powders onto active ingredient-free beads or neutral cores or active ingredient-containing particles and

applying the inner coating layer and the outer coating layer in the form of an aqueous dispersion or an organic solution in a spray process or by fluidized bed spray granulation.

15. A sustained release pharmaceutical or nutraceutical composition with resistance against the influence of ethanol and with resistance against the influence of calcium ions, comprising the pharmaceutical or nutraceutical composition according to claim 1.