ADHESIVE COMPOSITIONS FOR THE TREATMENT OF XEROSTOMIA

• US 20100247644A1
• Filed: 04/09/2010
• Published: 09/30/2010
• Est. Priority Date: 08/24/2007
• Status: Active Grant

• Current Assignee: Axiomedic Limited
• Original Assignee: Axiomedic Limited
• Inventors: Brama, Benny, Mizrahi, Boaz, Domb, Abraham J.
• Granted Patent: US 9,161,909 B2
• Time in Patent Office: Days
• US Class Current: 424/465
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Compositions for the treatment of xerostomia, and methods of making and using thereof are disclosed herein. The compositions are typically in the form of a film or tablet, such as a double layer sticker tablet. The compositions adhere to a buccal surface or mucosal surface in the oral cavity for at least 15 minutes, preferably for at least 30 minutes. The compositions themselves are able to increase the levels of saliva in the mouth without the need for active agents, such sialogogic agents. The compositions optionally contain a non-lipid lubricant, a flavoring agent, and/or a buffering agent. The composition is generally effective at treating or ameliorating the effects of xerostomia for a time period ranging from at least 30 minutes up to eight hours following administration to the buccal or oral mucosa.

Claims

1. A bioadhesive sticker tablet for treating or ameliorating the effects of xerostomia in a patient comprising a pharmaceutically acceptable bioadhesive carrier,

wherein the tablet, upon application to a mucosal surface, adheres to the mucosal tissue for at least 15 minutes;

and

wherein the tablet does not completely dissolve prior to about 15 minutes following application to a mucosal surface; and

wherein the tablet does not contain a sialogogic agent, a lipid, or combinations thereof; and

wherein salivary flow is increased 30 minutes following administration.

2. The tablet of claim 1, wherein the tablet is in the form of a single layer tablet.

3. The tablet of claim 1, wherein the tablet is in the form of a double layer tablet.

4. The tablet of claim 3, wherein the first layer and the second layer of the double layer tablet comprise one or more bioadhesive materials.

5. The tablet of claim 1, wherein the tablet dissolves following application to the mucosal surface over a period of time from about 15 minutes to about eight hours.

6. The tablet of claim 1, further comprising a flavoring agent, a binder, or a buffering agent, or a combination thereof.

7. The tablet of claim 1, further comprising a lubricant.

8. The tablet of claim 7, further comprising a lubricant in a therapeutically effective amount to lubricate the mouth following administration.

9. The tablet of claim 8, wherein the lubricant is selected from the group consisting of triglycerides or phospholipids.

10. The tablet of claim 8, wherein the lubricant is selected from the group consisting of polyvinyl pyrrolidone, magnesium stearate, or esterified polyacrylic acid polymers.

11. The tablet of claim 1, wherein a mucoadhesive is present in at least five percent by weight.

12. The tablet of claim 11, wherein the mucoadhesive is selected from the group consisting of copolymers of acrylic or methacrylic acid;

esterified polyacrylic acid polymers;

maleic acid copolymers;

polysaccharides;

hydrocolloid gels prepared from polysaccharides extracted from Fronia elephantum, Sapindus trifoliatus, Kunjac, and the cashew tree;

cellulose;

cellulose derivatives;

or combinations thereof.

13. The tablet of claim 12, wherein the mucoadhesive comprises a polyacrylic acid polymer crosslinked with a polyalkenyl polyether and hydroxypropyl cellulose.

14. The tablet of claim 1 having a mass of from about 50 mg to about 1000 mg.

15. The tablet of claim 1 having a surface area from about 0.4 cm² to about 30 cm² or has a diameter of up to three cm.

16. A method for treating or ameliorating the effects of xerostomia in a patient, comprising:

administering on the buccal or oral mucosa of the mouth of the patient an adhesive tablet comprising a mucoadhesive present in an amount of at least five percent by weight, effective to adhere the tablet to the mucosa for at least about 15 minutes following administration,

wherein the tablet does not completely dissolve prior to about 15 minutes following administration, and

wherein xerostomia is alleviated for at least about 30 minutes following administration, and

wherein salivary flow is increased about 30 minutes following administration.

17. The method of claim 16, wherein the tablet is placed on the palate or the cheek.

18. The method of claim 16, wherein the tablet adheres to the buccal or oral mucosa for between about 15 minutes and about eight hours.

19. The method of claim 16, wherein the tablet dissolves following application to the mucosal surface over a period of time ranging from about 15 minutes to about eight hours.

20. The method of claim 16, further comprising a lubricant in a therapeutically effective amount to lubricate the mouth following administration.

21. The method of claim 20, wherein the lubricant is selected from the group consisting of triglycerides or phospholipids.

22. The method of claim 20, wherein the lubricant is selected from the group consisting of polyvinyl pyrrolidone, magnesium stearate, or esterified polyacrylic acid polymers.

23. The method of claim 16, wherein the mucoadhesive is selected from the group consisting of copolymers of acrylic or methacrylic acid;

esterified polyacrylic acid polymers;

maleic acid copolymers;

polysaccharides;

hydrocolloid gels prepared from polysaccharides extracted from Fronia elephantum, Sapindus trifoliatus, Kunjac, and the cashew tree;

cellulose;

cellulose derivatives;

or combinations thereof.

24. The method of claim 23, wherein the mucoadhesive comprises a polyacrylic acid polymer crosslinked with a polyalkenyl polyether and hydroxypropyl cellulose.