Film-shaped or wafer-shaped pharmaceutical preparation with masked taste

• US 7,615,235 B2
• Filed: 02/04/2003
• Issued: 11/10/2009
• Est. Priority Date: 02/21/2002
• Status: Active Grant

• Current Assignee: LTS Lohmann Therapie-Systeme AG
• Original Assignee: LTS Lohmann Therapie-Systeme AG
• Inventors: Von Falkenhausen, Christian, Seibertz, Frank, Rademacher, Tina, Brandt, Petra, Krumme, Markus
• Primary Examiner(s): TRAN, SUSAN T
• Application Number:
  US10/505,317
• Publication Number:
  US 20050163830A1
• Time in Patent Office: 2,471 Days
• Field of Search: None
• US Class Current: 424/441
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0007 Effervescent A61K9/0065 takes precedence
• 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 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence

Abstract

The invention relates to thin film-shaped or wafer-shaped pharmaceutical preparations for oral administration of active substances. The preparations contain at least one matrix-forming polymer which has at least one active substance and at least one carbon dioxide-forming substance dissolved or dispersed therein.

Claims

1. A method for orally administering a film-shaped or wafer-shaped pharmaceutical mucoadhesive preparation the preparation being not capable of disintegrating in an aqueous medium, and the preparation containing at least one matrix-forming polymer comprising both at least one active substance having an unpleasant taste and at least one carbon dioxide forming substance which is not combined with an acid, wherein said unpleasant taste of said at least one active substance is reduced or suppressed, said method comprising the steps of:

providing said pharmaceutical preparation which contains the at least one matrix-forming polymer comprising the at least one unpleasant taste active substance and the at least one carbon dioxide forming substance dissolved or dispersed therein, wherein said at least one carbon dioxide forming substance which is not combined with an acid;

applying said preparation to a surface of the oral mucosa of a human or animal organism; and

removing the preparation from the oral mucosa of a human or animal organism after the active substance has been released.

2. The method according to claim 1, wherein the at least one carbon dioxide-forming substance is selected from the group consisting of sodium hydrogencarbonate, sodium carbonate, potassium carbonate and potassium hydrogen carbonate.

3. The method according to claim 1, wherein the preparation contains said at least one carbon dioxide-forming substance in an amount of 2 to 50%-wt relative to the pharmaceutical preparation.

4. The method according to claim 3 wherein the preparation contains said at least one carbon dioxide-forming substance in an amount of 5 to 30%-wt relative to the pharmaceutical preparation.

5. The method according to claim 4 wherein the preparation contains said at least one carbon dioxide-forming substance in an amount of 7 to 20%-wt relative to the pharmaceutical preparation.

6. The method according to claim 1, wherein the preparation further comprises at least one additional substance selected from the group consisting of at least one permeation enhancer and at least one blood flow stimulator.

7. The method according to claim 6, wherein the at least one permeation enhancer is selected from the group consisting of saturated fatty acids, unsaturated fatty acids, hydrocarbons, straight-chain or branched fatty alcohols, dimethyl sulfoxide, propylene glycol, decanol, dodecanol, 2-octyldodecanol, glycerol, isopropylidene glycerol, transcutol (=diethyleneglycol-monoethyl ether), DEBT (N,N-diethyl-m-tolueneamide), solketal, ethanol or other alcohols, menthol and other essential oils or components of essential oils, lauric acid diethanolamide, D-alpha-tocopherol and dexpanthenol.

8. The method according to claim 6, wherein the at least one blood flow stimulator is selected from the group consisting of menthol, eucalyptol, ginkgo extract, geranium oil, camphor, spearmint oil, oil of juniper, and rosemary.

9. The method according to claim 1, wherein the at least one matrix-forming polymer is selected from the group consisting of cellulose ether, polyvinyl alcohol, polyurethane, polymethacrylate, polymethyl methacrylate and derivatives and copolymerisates of each of said polymers.

10. The method according to claim 9, wherein the cellulose ether is ethyl cellulose.

11. The method according to claim 1, wherein the pharmaceutical preparation further comprises an auxiliary substance for imparting mucoadhesive properties to the preparation.

12. The method according to claim 11, wherein the pharmaceutical preparation includes a bilayer or multilayer structure having at least one layer in contact with the oral mucosa of a human or animal organism, wherein the at least one layer in contact with the oral mucosa is mucoadhesive, and at least one non-mucoadhesive layer.

13. The method according to claim 12, wherein the at least one non-mucoadhesive layer has a lower permeability for said at least one active substance.

14. The method according to claim 1, wherein the preparation is flat-shaped having a density between 0.3 g/cm³ and 1.7 g/cm³.

15. The method according to claim 14, wherein the preparation has a density between 0.5 g/cm³ and 1.5 g/cm³.

16. The method according to claim 15, wherein the preparation has a density between 0.7 g/cm³ and 1.3 g/cm³.

17. The method according to claim 1, wherein the total thickness of the preparation is 5 μ

m to 10 mm.

18. The method according to claim 17, wherein the total thickness of the preparation is 30 μ

m to 2 mm.

19. The method according to claim 18, wherein the total thickness of the preparation is 0.1 mm to 1 mm.

20. The method according to claim 1, wherein the preparation has a shape selected from the group consisting of round, ellipsoid, oval, triangular, quadrangular polygonal, and irregular rounded.

21. The method according to claim 1, wherein the preparation is present as a solidified foam having a density between 0.01 g/cm³ and 0.8 g/cm³.

22. The method according to claim 21, wherein the solidified foam has a density between 0.08 g/cm³ and 0.4 g/cm³.

23. The method according to claim 22, wherein the solidified foam has a density between 0.1 g/cm³ and 0.3 g/cm³.

24. The method according to claim 1, wherein the polymer portion of the matrix has a weight at least between 3%-wt. and 98%-wt relative to the entire preparation.

25. The method according to claim 24, wherein the polymer portion of the matrix has a weight at least between 7 to 80%-wt. relative to the entire preparation.

26. The method according to claim 25, wherein the polymer portion of the matrix has a weight at least between 20 to 50%-wt. relative to the entire preparation.

27. The method according to claim 1, wherein the preparation further comprises at least one additional auxiliary substance selected from the group consisting of fillers, colourants, disintegrants, emulsifiers, plasticizers, sweeteners, preserving agents, stabilisers, antioxidants and flavouring agents.

28. The method according to claim 1, wherein the preparation further comprises at least one flavouring agent, at least one sweetener, or at least one plasticizer.