Nicotine-containing oral dosage form

• US 20040101543A1
• Filed: 09/10/2003
• Published: 05/27/2004
• Est. Priority Date: 03/22/2002
• Status: Abandoned Application

• Current Assignee: Smithkline Beecham Corporation (Smithkline Beecham PLC)
• Original Assignee: Smithkline Beecham Corporation (Smithkline Beecham PLC)
• Inventors: Liu, John, Platcow, Stuart, Lech, Stanley J.
• Application Number:
  US10/471,477
• Publication Number:
  US 20040101543A1
• Time in Patent Office: Days
• US Class Current: 424/434
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof

Abstract

The present invention is directed to glassy matrix solid oral dosage forms useful for transmucosal oral administration of a nicotine active.

Claims

1. A solid, oral dosage form useful for transmucosal oral administration of a nicotine active, comprising:

a) a glassy matrix comprising at least one substantially non-hygroscopic sugar alcohol capable of forming a glassy structure; and

b) a nicotine active in an amount effective to reduce nicotine cravings.

2. A dosage form of claim 1 wherein the sugar alcohol comprises a mixture of 1,6-GPS (6-O-α

-D-glucopyranosyl-D-sorbitol) and 1,1-GPM (1-O-α

-D-glucopyranosyl-D-mannitol) in a weight ratio of from about 99;

1 to about 1;

99.

3. A dosage form of claim 1 comprising at least about 50% of the sugar alcohol, based on the weight of the dosage form.

4. A dosage form of claim 1 wherein the nicotine active is selected from nicotine, derivatives of nicotine, and combinations thereof.

6. A dosage form of claim 2 or 5 wherein the sugar alcohol comprises a mixture of 1,6-GPS and 1,1-GPM in a weight ratio of from about 70:

30 to about 30;

70.

7. A dosage form of claim 6 wherein the sugar alcohol comprises a mixture of 1,6-GPS and 1,1-GPM in a weight ratio of from about 60:

40 to about 40;

60.

8. A dosage form of claim 7 wherein the sugar alcohol mixture is ISOMALT.

9. A dosage form of claim 4 or 5 further comprising a buffer in an amount effective to provide an alkaline mouth saliva pH.

18. A dosage form of claim 1, 5 or 10 further comprising a non-pharmacological component for providing a sensory signal effective to provide rapid nicotine craving relief.

19. A dosage form of claim 1, 5 or 10 in the form of a lozenge.

20. A method of reducing nicotine cravings comprising orally administering a dosage form of claim 1, 5 or 10 to a person in need of nicotine craving reduction.

21. A method of claim 20 wherein a nicotine active blood plasma concentration of at least about 6 ng/ml is achieved after starting oral administration of the dosage form.

22. A method of claim 20 wherein a sustained nicotine active blood plasma concentration of from about 6 ng/ml to about 35 ng/ml is achieved after starting oral administration of the composition.

23. A method of claim 21 or 22 wherein the nicotine active is selected from nicotine, derivatives of nicotine, and combinations thereof.

24. A method of reducing tobacco usage comprising orally administering a dosage form of claim 1, 5 or 10 to a person in need of reducing tobacco usage.

5. A solid, oral dosage form useful for transmucosal oral administration of a nicotine active, comprising:

a) a glassy matrix comprising at least about 50%, based on the weight of the dosage form, of a sugar alcohol mixture comprising 1,6-GPS (6O-α

-D-glucopyranosyl-D-sorbitol) and 1,1-GPM (1-O-α

-D-glucopyranosyl-D-mannitol) in a weight ratio of from about 99;

1 to about 1;

99; and

b) a nicotine active in an amount effective to reduce nicotine cravings, selected from nicotine, derivatives of nicotine, and combinations thereof.

10. A solid, oral dosage form useful for transmucosal oral administration of a nicotine active, comprising:

a) a glassy matrix comprising at least about 50%, based on the weight of the dosage form, of a sugar alcohol mixture which is ISOMALT;

b) a nicotine active in an amount effective to reduce nicotine cravings, selected from nicotine, derivatives of nicotine, and combinations thereof; and

c) a buffer in an amount effective to provide an alkaline mouth saliva pH.

11. A dosage form of claim 3, 5 or 10 comprising at least about 70% of the sugar alcohol mixture, based on the weight of the dosage form.

12. A dosage form of claim 11 comprising at least about 85% of the sugar alcohol mixture, based on the weight of the dosage form.

13. A dosage form of claim 4, 5 or 10 wherein the nicotine active is selected from nicotine oil, nicotine bitartrate, nicotine polacrilex and combinations thereof.

14. A dosage form of claim 4, 5 or 10 comprising from about 0.5 mg to about 5 mg of the nicotine active per dosage unit.

15. A dosage form of claim 9 or 10 wherein the buffer is selected from sodium carbonate, sodium bicarbonate, calcium carbonate, potassium carbonate, potassium bicarbonate, sodium phosphate dibasic, sodium phosphate tribasic, potassium phosphate dibasic, potassium phosphate tribasic, and combinations thereof.

16. A dosage form of claim 15 wherein the buffer is selected from sodium carbonate, potassium carbonate, and combinations thereof.

17. A dosage form of claim 3, 5 or 10 wherein the glassy matrix further comprises from about 1% to about 20%, based on the weight of the dosage form, of one or more compounds selected from the group consisting of sucrose, sorbitol, and xylitol.

25. A solid, oral dosage form useful for transmucosal oral administration of a nicotine active, wherein the dosage form provides a nicotine active blood plasma concentration of at least about 6 ng/ml after starting oral administration of the dosage form.

27. A dosage form of claim 25 or 26 wherein the nicotine active is selected from nicotine, derivatives of nicotine, and combinations thereof.

26. A solid, oral dosage form useful for transmucosal oral administration of a nicotine active, wherein the dosage form provides a sustained nicotine active blood plasma concentration of from about 6 ng/ml to about 35 ng/ml after starting oral administration of the dosage form.