Multilayer preparation in film form, consisting of hydrophilic polymers, for the rapid release of active ingredients

• US 7,332,230 B1
• Filed: 11/03/2000
• Issued: 02/19/2008
• Est. Priority Date: 11/11/1999
• Status: Expired due to Term

• Current Assignee: LTS Lohmann Therapie-Systeme AG
• Original Assignee: LTS Lohmann Therapie-Systeme AG
• Inventors: Krumme, Markus
• Primary Examiner(s): Dye; Rena
• Assistant Examiner(s): FERGUSON, LAWRENCE D
• Application Number:
  US10/129,835
• Time in Patent Office: 2,664 Days
• Field of Search: 424/434, 424/439, 424/408, 424/413, 424/480, 424/435, 424/444, 424/407, 424/426, 424/495, 514/772.2, 514/781, 428/147, 428/516, 428/520, 428/420, 428/424.6
• US Class Current: 428/516
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: Y10T 428/31913 Monoolefin polymer
• CPC Class Codes: Y10T 428/31928 Ester, halide or nitrile of addition polymer

Abstract

A multilayer preparation in the form of films of hydrophilic polymers for rapid release of substances present in the film layers into liquid surroundings is characterized in that adjacent layers differ from one another in that in each case one layer is soluble in a nonaqueous solvent in which the respective adjacent layer is insoluble or only slightly soluble.

Claims

1. A multilayer preparation in the form of films of hydrophilic polymers for rapid release of substances present in the film layers into liquid surroundings, consisting essentially of:

a composite formed from at least two film layers, adjacent film layers being different from one another in that in each case one of said layers is soluble in a nonaqueous solvent in which the respective adjacent layer is insoluble or only slightly soluble, and the layer soluble in a nonaqueous solvent is formed from polyvinylpyrrolidone or a mixture comprising polyvinylpyrrolidone, and the insoluble or only slightly soluble adjacent layer is formed from polyvinyl alcohol or a mixture comprising polyvinyl alcohol.

2. The preparation according to claim 1, wherein the film layers are soluble in water, aqueous fluids, human fluids or animal fluids, irrespective of the solubility of the film layers in nonaqueous systems.

3. The preparation according to claim 1, wherein the substances which can be released from the film layer are selected from the group consisting of pharmaceutically active ingredients, substances with refreshing effect, flavoring, odorizers and sweeteners.

4. The preparation according to claim 1, wherein the release of the substances from the film layers is brought about by dissolution of these layers by physiological liquids, artificial simulations of physiological liquids, human body fluids or animal body fluids.

5. The preparation according to claim 1, wherein the time required for dissolution of a preparation with an area not exceeding 10 cm² in physiological fluids, or artificial simulations of such fluids, does not exceed 15 min.

6. The preparation according to claim 1, wherein at least one layer contains at least one pharmacologically active substance.

7. The preparation according to claim 1, wherein at least two layers contain the same substance, the same pharmacologically active ingredient, or the same mixture of these substances.

8. The preparation according to claim 1, wherein at least two layers contain releasable substances or pharmacologically active ingredients which are different from one another.

9. The preparation according to claim 1, wherein the preparation is composed of two water-soluble layers, with one layer additionally being soluble in at least one organic solvent, in which the other layer is insoluble.

10. The preparation according to claim 1, wherein the preparation is composed of three water-soluble layers, with two outer layers additionally being soluble in at least one-organic solvent, in which the middle layer is insoluble.

11. The preparation according to claim 1, which further comprises hydrophilic film-forming polymers selected from the group consisting of cellulose ethers, polyvinyl acetate, a copolymer of a cellulose ether, a copolymer of polyvinyl acetate, polyethylene glycols, alginates, gelatin and other substances of synthetic, semisynthetic or natural origin.

12. The preparation according to claim 1, wherein at least one of the layers contains auxiliaries or additives which are selected from the group consisting of plasticizers, pigments, disintegration promoters, wetting agents, absorption- or permeation-promoting substances, structuring agents and texture modifiers.

13. The preparation according to claim 1, wherein the thickness of the multilayer preparation in the form of films is at least 100 μ

m.

14. The preparation according to claim 1, wherein the time required for dissolution of a preparation with an area not extending 10 cm² in physiological fluids, or artificial simulations of such fluids, does not exceed 5 min.

15. The preparation according to claim 1, wherein the time required for dissolution of a preparation with an area not exceeding 10 cm² in physiological fluids, or artificial simulations of such fluids, does not exceed 1 min.

16. The preparation according to claim 1, wherein the thickness of the multilayer preparation in the form of films is at least 150 μ

m.

17. A multilayer preparation in the form of films of hydrophilic polymers for rapid release of substances present in the film layers into liquid surroundings, consisting of:

a composite formed from at least two film layers, adjacent film layers being different from one another in that in each case one of said layers is soluble in a nonaqueous solvent in which the respective adjacent layer is insoluble or only slightly soluble, and the layer soluble in a nonaqueous solvent is formed from polyvinylpyrrolidone or a mixture comprising polyvinylpyrrolidone, and the insoluble or only slightly soluble adjacent layer is formed from polyvinyl alcohol or a mixture comprising polyvinyl alcohol.

18. The preparation according to claim 17, wherein the film layers are soluble in water, aqueous fluids, human fluids or animal fluids, irrespective of the solubility of the film layers in nonaqueous systems.

19. The preparation according to claim 17, wherein the substances which can be released from the film layer are selected from the group consisting of pharmaceutically active ingredients, substances with refreshing effect, flavoring, odorizers and sweeteners.

20. The preparation according to claim 17, wherein the release of the substances from the film layers is brought about by dissolution of these layers by physiological liquids, artificial simulations of physiological liquids, human body fluids or animal body fluids.

21. The preparation according to claim 17, wherein the time required for dissolution of a preparation with an area not exceeding 10 cm² in physiological fluids, or artificial simulations of such fluids, does not exceed 15 min.

22. The preparation according to claim 17, wherein at least one layer contains at least one pharmacologically active substance.

23. The preparation according to claim 17, wherein at least two layers contain the same substance, the same pharmacologically active ingredient, or the same mixture of these substances.

24. The preparation according to claim 17, wherein at least two layers contain releasable substances or pharmacologically active ingredients which are different from one another.

25. The preparation according to claim 17, wherein the preparation is composed of two water-soluble layers, with one layer additionally being soluble in at least one organic solvent, in which the other layer is insoluble.

26. The preparation according to claim 17, wherein the preparation is composed of three water-soluble layers, with the two outer layers additionally being soluble in at least one organic solvent, in which the middle layer is soluble.

27. The preparation according to claim 17, which further comprises hydrophilic film-forming polymers selected from the group consisting of cellulose ethers, polyvinyl acetate, a copolymer of a cellulose ether, a copolymer of polyvinyl acetate, polyethylene glycols, alginates, gelatin and other substances of synthetic, semisynthetic or natural origin.

28. The preparation according to claim 17, wherein at least one of the layers contains auxiliaries or additives which are selected from the group consisting of plasticizers, pigments, disintegration promoters, wetting agents, absorption- or permeation-promoting substances, structuring agents and texture modifiers.

29. The preparation according to claim 17, wherein the thickness of the multilayer preparation in the form of films is at least 100 μ

m.

30. The preparation according to claim 17, wherein the time required for dissolution of a preparation with an area not exceeding 10 cm² in physiological fluids, or artificial simulations of such fluids, does not exceed 1 min.

31. The preparation according to claim 17, wherein the time required for dissolution of a preparation with an area not exceeding 10 cm² in physiological fluids, or artificial simulations of such fluids, does not exceed 1 min.

32. The preparation according to claim 17, wherein the thickness of the multilayer preparation in the form of films is at least 150 μ

m.