Gastric resistant pharmaceutical or nutraceutical composition with resistance against the influence of ethanol

• US 10,639,283 B2
• Filed: 10/18/2012
• Issued: 05/05/2020
• Est. Priority Date: 08/27/2012
• Status: Expired due to Fees

• Current Assignee: Evonik Operations GmbH (Rag-Stiftung)
• Original Assignee: Evonik Operations GmbH (Rag-Stiftung)
• Inventors: Haksar, Priyanka Bansilal, Joshi, Shraddha Sanjeev, Shah, Harsh, Patil, Preeti, Shetty, Smitha
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): Singh, Randeep
• Application Number:
  US14/416,500
• Publication Number:
  US 20150209298A1
• Time in Patent Office: 2,756 Days
• Field of Search: None
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 9/2846 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 9/5047 Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5089 Processes

Abstract

A pharmaceutical or nutraceutical composition with a core, an inner layer, and an outercoating layer, wherein a pharmaceutical or a nutraceutical active ingredient is contained in the core, at least 30% by weight of a salt of alginic acid is contained in the inner layer, and at least 30% by weight of a polymer or copolymer with anionic side groups is contained 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 at least 30% by weight of a salt of alginic acid selected from the group consisting of sodium alginate, potassium alginate, magnesium alginate and lithium alginate and a mixture thereof and up to 60% by weight of a glidant and wherein said inner coating layer does not comprise ammonium alginate, and

c) an outer coating layer comprising at least 30% by weight of a polymer or a copolymer comprising anionic side groups,

wherein the anionic polymer or copolymer in the outer coating layer is selected from the group consisting of (meth)acrylate copolymers or hydroxypropylmethyl cellulose acetate succinate

which is gastric resistant, and resistant against the influence of ethanol and the influence of calcium ions.

2. The pharmaceutical or nutraceutical composition according to claim 1, wherein the amount of the inner coating layer is equal or higher than the amount of the outer coating layer.

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 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, which is gastric resistant, and wherein the inner and/or the outer coating layer comprises up to 60% 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 is not more than 10% under in-vitro conditions at pH 1.2 for 2 hours in a buffered medium according to USP with and without the addition of 40% v/v ethanol.

7. The pharmaceutical or nutraceutical composition according to claim 1, wherein the release of the pharmaceutical or nutraceutical active ingredient is not more than 10% under in-vitro conditions at pH 1.2 for 2 hours in a buffered medium according to USP with and without 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 is at least 75% under in-vitro conditions at pH 6.8 or at pH 7.5 for 45 min in a buffered medium according to USP.

9. The pharmaceutical or nutraceutical composition according to claim 1, wherein the release of the pharmaceutical or nutraceutical active ingredient is at least 60% under in-vitro conditions at pH 5.5 for 90 min in a buffered medium according to USP.

10. The pharmaceutical or nutraceutical composition according to claim 1, wherein the polymer or copolymer comprising anionic side groups in the outer coating layer comprises 25 to 95 by weight free-radical polymerized C₁- to C₁₈-alkyl esters of acrylic or of methacrylic acid and 75 to 5% by weight (meth)acrylate monomers comprising an anionic group.

11. The pharmaceutical or nutraceutical composition according to claim 1, which 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.

12. 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, 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.

13. The pharmaceutical or nutraceutical composition according to claim 1, wherein said outer coating layer comprises at least 30% by weight of a polymer or a copolymer comprising anionic carboxyl side groups.

14. The pharmaceutical or nutraceutical composition according to claim 1, wherein

the composition is a coated pellet or coated granule with a size of from 50 to 1000 μ

m, having from 2 to 50 mg of the salt of alginic acid per square centimeter, or

the composition is a coated tablet, a coated minitablet, or a coated capsule with a size of greater than 1 and up to 25 mm, having from 0.5 to 10 mg of the salt of alginic acid per square centimeter.

15. The pharmaceutical or nutraceutical composition according to claim 1, wherein the release of the pharmaceutical or nutraceutical active ingredient is not more than 10% under in-vitro conditions at pH 1.2 for 2 hours in a buffered medium according to USP with and without the addition of 40% v/v ethanol, and with and without the addition of 1.25 mM calcium-ions.

16. The pharmaceutical or nutraceutical composition according to claim 14, wherein the release of the pharmaceutical or nutraceutical active ingredient is not more than 10% under in-vitro conditions at pH 1.2 for 2 hours in a buffered medium according to USP with and without the addition of 40% v/v ethanol, and with and without the addition of 1.25 mM calcium-ions.

17. A process for controlled release of a pharmaceutical or nutraceutical to a patient in need thereof comprising orally administering to a patient in need there of the pharmaceutical or nutraceutical composition according to claim 1.