Active ingredient-containing floating forms comprising polyvinyl acetate and polyvinylpyrrolidone, their use and production

• US 6,635,279 B2
• Filed: 03/20/2001
• Issued: 10/21/2003
• Est. Priority Date: 03/27/2000
• Status: Expired due to Term

• Current Assignee: BASF AG (BASF SE)
• Original Assignee: BASF AG (BASF SE)
• Inventors: Kolter, Karl, Ascherl, Hermann, Schönherr, Michael
• Primary Examiner(s): Spear, James M.
• Application Number:
  US09/811,434
• Publication Number:
  US 20030021846A1
• Time in Patent Office: 945 Days
• Field of Search: 424/464, 424/465, 424/457, 424/474, 424/472, 424/470, 424/468
• US Class Current: 424/468
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Abstract

The present invention relates to oral dosage forms comprising

a) one or more active ingredients

b) a formulated mixture of polyvinyl acetate and polyvinylpyrrolidone

c) where appropriate other excipients customary for producing the dosage form,

wherein they float on gastric fluid and display delayed release of active ingredient, and to the use and production thereof.

Claims

1. An oral dosage form comprising

a) one or more active ingredients

b) a formulated mixture of polyvinyl acetate and polyvinylpyrrolidone

c) where appropriate other excipients customary for producing the dosage form,

which floats on gastric fluid and displays delayed release of active ingredient, wherein the proportion of the formulated mixture of polyvinyl acetate and polyvinylpyrrolidone is between 20 and 70%, based on the total weight of the oral dosage form.

2. A dosage form as claimed in claim 1, wherein the ratio of polyvinyl acetate to polyvinylpyrrolidone is from 6:

4 to 9;

1.

3. A dosage form as claimed in claim 1, wherein the oral dosage form is a tablet, capsule or a coated tablet.

4. A dosage form as claimed in claim 1, wherein the dosage form is a tablet.

5. A dosage form as claimed in claim 1, wherein the release is adjusted by adding substances which are freely soluble in water, soluble in water, highly swelling or lipophilic.

6. A dosage form as claimed in claim 1, wherein the friability is less than 3%.

7. A dosage form as claimed in claim 1, wherein a water-soluble or water-insoluble, release-slowing coating is applied to the oral dosage form.

8. A dosage form as claimed in claim 5, wherein the highly swelling substances which are soluble in water are selected from the group consisting of alginates, pectins, galactomannans, carrageenans, dextran, curdlan, pullulan, gellan, chitin, gelatin, xanthans, hemicelluloses, cellulose derivatives, starch derivatives, and derivatives thereof, and the lipophilic substances are selected from the group consisting of fatty alcohols, fatty acids, and lipophilic polymers.

9. A dosage form as claimed in claim 8, wherein the highly swelling substances which are soluble in water are selected from the group consisting of methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, carboxymethylcellulose, carboxymethyl starch, degraded starch, maltodextrins, polyacrylic acid, polymethacrylic acid, acrylic acid/methacrylic acid copolymers, polyvinyl alcohols, high molecular weight polyethylene glycols, polyoxyethylene/polyoxypropylene block copolymers, high molecular weight polyvinylpyrrolidones, and derivatives thereof.

10. A dosage form as claimed in claim 5, wherein the substances which are soluble in water are selected from the group consisting of polyethylene glycols, polyvinylpyrrolidone and vinylpyrrolidone/vinyl acetate copolymers.

11. A dosage form as claimed in claim 5, wherein the lipophilic substances are selected from the group consisting of stearyl alcohol, stearic acid, glycerides, fatty acid esters, fatty alcohol esters, ethylcellulose, cellulose acetate, acrylic ester/methacrylic ester copolymers, methacrylic acid/acrylic ester copolymers, cellulose acetate phthalate, cellulose acetate succinate, hydroxypropylmethylcellulose acetate phthalate, and hydroxypropylmethylcellulose acetate succinate.

12. A dosage form as claimed in claim 1, which comprises as other excipients c) lubricants, binders, disintegrants, flow regulators, stabilizers, colorants or bulking agents.

13. A dosage form as claimed in claim 1, which comprises as active ingredients a) food supplements or additives, vitamins, minerals or trace elements or active pharmaceutical ingredients.

14. A dosage form as claimed in claim 1, which comprises as active ingredients a) active pharmaceutical ingredients.

15. A dosage form as claimed in claim 1, wherein the active pharmaceutical ingredient is selected from the group consisting of benzodiazepines, antihypertensives, vitamins, cytostatics, anesthetics, neuroleptics, antidepressants, antibiotics, antimycotics, fungicides, chemotherapeutics, urologicals, platelet aggregation inhibitors, sulfonamides, spasmolytics, hormones, immunoglobulins, sera, thyroid therapeutics, psychopharmaceuticals, antiparkinson agents, other antihyperkinetics, ophthalmologicals, neuropathy products, calcium metabolism regulators, muscle relaxants, lipid-lowering agents, liver therapeutics, coronary agents, cardiac agents, immunotherapeutics, regulatory peptides, regulatory peptide inhibitors, hypnotics, sedatives, gynecologicals, antigout agents, fibrinolytics, enzyme products, transport proteins, enzyme inhibitors, emetics, perfusion promoters, diuretics, diagnostics, corticoids, cholinergics, biliary therapeutics, antiasthmatics, bronchiospasmolytics, beta-receptor blockers, calcium channel blockers, ACE inhibitors, arteriosclerosis remedies, antiinflammatory agents, anticoagulants, antihypotensives, antihypoglycemics, antifibrinolytics, antiepileptics, antiemetics, antidotes, antidiabetics, antiarrhythmics, antianemics, antiallergics, anthelmintics, analgesics, analeptics, aldosterone antagonists, and weight-reducing agents.

16. A dosage form as claimed in claim 1, wherein two or more layers are present and differ in the content of active ingredient and formulated mixture of polyvinyl acetate and polyvinylpyrrolidone.

17. A dosage form as claimed in claim 1, which is a press-coated tablet with a core with a very high active ingredient content.

18. A process for producing oral dosage forms as claimed in claim 1, which comprises tableting an initial mixture of the dosage form components using a pressure of less than 100 MPa.

19. A process for producing oral dosage forms as claimed in claim 18, wherein the initial mixture is tableted directly or the initial mixture or a part thereof is wet-granulated or dry-compacted before the tableting.

20. A drug product for delayed release of active ingredient, which is an oral dosage form as claimed in claim 1.

21. A process for producing drug products with delayed release of active ingredient for treating diseases, comprising incorporating the active ingredient into the oral dosage form as claimed in claim 1.

22. The process as claimed in claim 21, wherein the active ingredient is selected from the group consisting of food supplements, food additives, vitamins, minerals, trace elements, and active pharmaceutical ingredients.