Double-Layered Absorbable Solid Compositions for the Topical Treatment of Oral Mucosal Disorders

• US 20070104783A1
• Filed: 12/15/2006
• Published: 05/10/2007
• Est. Priority Date: 02/28/2001
• Status: Active Grant

• Current Assignee: Axiomedic Limited
• Original Assignee: Axiomedic Limited
• Inventors: Domb, Abraham, Wolnerman, Joseph
• Granted Patent: US 8,980,334 B2
• Time in Patent Office: Days
• US Class Current: 424/464
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
• CPC Class Codes: A61K 33/18 Iodine; Compounds thereof
• CPC Class Codes: A61K 36/18 Magnoliophyta (angiosperms)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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

Abstract

Bioadhesive sticker tablets which are applied directly to vaginal, rectal and/or oral mucosa are described herein. In one embodiment, the sticker tablets are applied directly to ulcers or lesions in the oral cavity. The compositions adhere immediately upon administration, swell over time, and remain adherent to the ulcer or lesion for at least 60 minutes. The compositions can be in the form of single layer, double layer, or multilayer sticker tablets. The compositions provide immediate pain relief to the patient and promote rapid healing of the ulcer or lesion. The sticker tablet compositions contain one or more bioadhesive polymers. In one embodiment, the polymers are crosslinked polycarboxylic acids and polyols. The compositions contain at least one herbal agent and/or irritating compound, and optionally, a non-herbal active agent. The compositions can deliver an non-irritating effective dose of the agent for at least 60 minutes. The compositions described herein are stable upon storage for six months or longer.

Claims

1. A solid, self-bioadhesive sticker tablet for topical application comprising

(a) a therapeutically effective amount to treat a mucosal disease of an active agent comprising at least one active agent selected from the group consisting of herbal agent, volatile compounds, irritating compounds, and combinations thereof;

and

(b) a pharmaceutically acceptable solid bioadhesive carrier in an amount from about 5 to 99 percent based on the weight of the composition,

wherein the composition is in the form of a compression molded tablet that, upon application to a mucosal surface, adheres to the mucosal tissue for at least 60 minutes, and

wherein the composition, upon adhesion to the mucosal tissue, releases an non-irritating effective dose of the active agent to treat the mucosal disease for a period of at least 60 minutes.

2. The sticker tablet of claim 1, wherein the composition is in the form of a disc or tablet having a diameter of about 2 mm to about 15 mm diameter and thickness of about 0.4 mm to about 2.3 mm.

3. The sticker tablet of claim 1, wherein the active agent is selected from the group consisting of anti-inflammatory agents, analgesic agents, antiaching agents, anesthetics, antimicrobial agents, antifungal agents, antiseptic agents, antiviral agents, antibiotic agents, antiparasitic agents, and combinations thereof.

4. The sticker tablet of claim 1, wherein the active agent is an herbal agent selected from the group consisting of bioactive herb extracts, tinctures, essential oils and combinations thereof.

8. The sticker tablet of claim 1 further comprising a non-herbal active agent selected from the group consisting of local anesthetics, analgesics, antivirals, antimicrobials, steroidal and non-steriodal anti-inflammatory agents, antihistamines or antiallergics, steroids, enzymes, vitamins, antipyretics, anti-malarial agents, anti-ulcer drugs, peptides, DNA plasmid and antisense based therapeutic agents, anti-proliferatives, antifungal agents, and combinations thereof.

9. The sticker tablet of claim 1, wherein the solid, bioadhesive carrier is selected from the group consisting of natural, semisynthetic or synthetic polyhydric polymers;

natural, semisynthetic or synthetic polycarboxylic acid polymers, and combinations thereof.

10. The sticker tablet of claim 9, wherein the polyhydric polymers are selected from the group consisting of hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethylcellulose, carboxymethyl cellulose, dextran, arabinogalactan, pullulan, gaur-gum, hyaluronic acid, pectins, starch derivatives, acrylic acid polymers and copolymers, polymers and copolymers of acrylic acid esters, polymers of vinyl alcohols, alkoxy polymers, polyethylene oxide polymers, polyethers, and mixtures thereof.

11. The sticker tablet of claim 10, wherein the polymers or copolymers of acrylic acid are crosslinked with polyalkenyl polyethers, cellulose derivatives, and combinations thereof.

12. The sticker tablet of claim 1 further comprising a hydrophobic coating on one side of the sticker tablet.

13. The sticker tablet of claim 1 further comprising one or more pharmaceutically acceptable excipients selected from the group consisting of fillers, tableting excipients, lubricants, enhancers, flavors, taste-masking agents, pH controlling compounds, dyes, stabilizers, lubricants, and combinations thereof.

14. The sticker tablet of claim 1 further comprising compounds selected from the group consisting of salts of bile acids, limonene, limonene derivatives, and combinations thereof.

15. The sticker table of claim 1, wherein the tablet is in the form of a double layer tablet.

16. The sticker tablet of claim 15, wherein the double layer tablet comprises one layer comprising the active agent and one or more pharmaceutically acceptable excipients and a second layer comprising one or more bioadhesive materials.

17. The sticker tablet of claim 15, wherein the double layer tablet comprises one layer comprising the active agent, one or more pharmaceutically acceptable excipients, and one or more bioadhesive materials and the second layer comprises one or more bioadhesive materials.

5. The sticker tablet of claim 5, wherein the active agent is an irritating compound selected from the group consisting of iodine and menthol.

6. The sticker tablet of claim 6, wherein the irritating compound is iodine.

7. The sticker tablet of claim 6, wherein the irritating compound is menthol.

18. The sticker tablet of claim 6, wherein the iodine is complexed to ethyl cellulose or hydroxymethyl cellulose.

19. A method for the preparation of a solid, self-bioadhesive sticker tablet for topical application that adheres to the oral mucosal tissue comprising the following steps:

(a) forming a solid powder comprising at least one at least one active agent selected from the group consisting of herbal agents, volatile compounds, irritating compounds, and combinations thereof;

(b) mixing the at least one active agent with one or more pharmaceutically acceptable excipients;

(c) mixing, in a separate container, bioadhesive materials; and

(d) compressing the mixtures of steps (b) and (c) into a double layer tablet.

20. The method according to claim 19, wherein the mixtures of steps (b) and (c) are compressed into a disc or tablet with a diameter of about 2 mm to about 15 mm and a thickness from about 0.4 mm to about 2.3 mm.

21. A method for topical treatment of a mucosal disorder, the method comprising administering to a patient in need thereof a composition comprising

(a) a therapeutically effective amount to treat a mucosal disease of an active agent comprising at least one at least one active agent selected from the group consisting of herbal agents, volatile compounds, irritating compounds, and combinations thereof;

and

(b) a pharmaceutically acceptable solid bioadhesive carrier in an amount from about 5 to 99 percent based on the weight of the composition

wherein the composition is in the form of a compression molded tablet that adheres to the oral mucosal tissue for at least 60 minutes, and

wherein, upon adhesion to the oral mucosal tissue, the volatile or irritating active agent is released from the sticker to the oral mucosal tissue in an non-irritating effective amount for a period of at least 60 minutes following application.

22. The method of claim 21, wherein the oral mucosal disorder is selected from the group consisting of oral mucositis (stomatitis), aphthous lesions, gingivitis, periodontis, and combinations thereof.

23. The method of claim 21, wherein the oral mucosal disorder is selected from the group consisting of herpes labialis (cold sores or fever blisters), herpes genitalis, herpes zoster (shingles), varicella zoster (chickenpox);

inflammatory diseases or diseases compromising the immune system such as aphthous stomatitis (canker sores), oral mucositis (stomatitis) secondary to chemotherapy, allergic conjunctivitis, giant papillary conjunctivitis; and

lesions of injury, thermal burns, pressure sores, and combinations thereof.