Tablettable chewing gums

Patent metadata

Field	Value
Publication number	US-9511021-B2
Application number	US-99318809-A
Country	US
Kind code	B2
Filing date	May 19, 2009
Priority date	May 21, 2008
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

The invention relates to certain nicotine chewing gums that provide for a high rate of buccal absorption and high plasma concentrations, in particular over the first 10 minutes after administration, in a subject willing to quit smoking.

First claim

The invention claimed is:

1. A stable chewing gum for use in nicotine replacement therapy comprising a coated core, the core comprising:
a compressible chewing gum base that is suitable for tableting at ambient temperature,
at least one nicotine active selected from the group consisting of pharmaceutically
acceptable salts of nicotine and pharmaceutically acceptable, cellulose-free, nicotine
complexes and resins,
at least one buffering agent in homogeneous mixture with the nicotine active, said at least one buffering agent comprising particles comprising a core of sodium bicarbonate and an outer layer of sodium carbonate,
whereby the core is tableted, and
a coating free of nicotine active comprising 80-95% maltitol and 0.5-3% peppermint oil (based on total coating mass).

2. A chewing gum according to claim 1 , wherein the at least one nicotine active is selected from the group consisting of pharmaceutically acceptable salts of nicotine.

3. A chewing gum according to claim 1 , which is characterized by comprising the at least one nicotine active in an amount corresponding to from 0.2 to 8 mg of nicotine free base.

4. A chewing gum according to claim 1 , wherein the coating comprises a binder selected from the group consisting of arabic gum, tragacanth gum, guar gum, acacia gum, xanthan gum, alginic acid, salts of alginic acid, gellan gum, glucomannan gum, carrageenan gum, karaya gum, locust bean gum, tara gum, gelatin and any mixtures thereof.

5. A chewing gum according to claim 1 , wherein the coating comprises a coating-plastifying substance selected from the group consisting of glycerol, polyethylene glycol, propylene glycol, povidone (polyvinyl pyrrolidone), copovidone (vinyl pyrrolidone vinyl acetate copolymer), hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, diethyl phthalate, dibutyl phthalate, diacetin, triacetin, triethyl citrate, dibutyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, 2 pyrrolidone and any mixtures thereof.

6. A chewing gum according to claim 1 , wherein rapid nicotine release means releasing in an in-vitro dissolution testing method (40 ml buffer pH 7.4, chewing jaw distance 1.6 mm - 20° rotation, 50 chewing movements per minute) at least 60% in 5 minutes (250 chews) , at least 70% in 10 minutes (500 chews) and more than 80% in 30 minutes (1500 chews) of the total nicotine content.

7. A chewing gum according to claim 1 , wherein rapid nicotine release means in-vivo delivering to the mouth of a patient at least 80% of the original amount of nicotine originally being present in said chewing gum over a time period of 30 mm starting with administering said chewing gum.

8. A chewing gum according to claim 1 , having a mean plasma concentration C (5 min) of from 1 up to 6 ng/ml.

9. A chewing gum according to claim 1 , having a plasma concentration C (10 min) of from 3 up to 14 ng/ml.

10. A chewing gum according to claim 1 , having a mean AUC (0-10 min) of from 0.2 up to 0.9 ng×h/ml.

11. A chewing gum according to claim 1 , capable of reaching a mean AUC (0-20 min) of from 0.8 up to 3.2 ng×h/ml.

12. A chewing gum according to claim 1 , wherein the coating additionally comprises a binder comprising a gum.

13. A chewing gum according to claim 12 , wherein the coating additional comprises a coating-plastifying substance comprising glycerol.

14. A stable chewing gum for use in nicotine replacement therapy comprising a coated core, the core comprising:
a compressible chewing gum base that is suitable for tableting at ambient temperature,
at least one nicotine active selected from the group consisting of pharmaceutically
acceptable salts of nicotine and pharmaceutically acceptable, cellulose-free, nicotine
complexes and resins,
at least one buffering agent in homogeneous mixture with the nicotine active, said at least one buffering agent comprising particles comprising a core of sodium bicarbonate and an outer layer of sodium carbonate,
a binder selected from the group consisting of arabic gum, tragacanth gum, guar gum, acacia gum, xanthan gum, alginic acid, salts of alginic acid, gellan gum, glucomannan gum, carrageenan gum, karaya gum, locust bean gum, tara gum, gelatin and any mixtures thereof,
whereby the core is tableted, and
a coating free of nicotine active comprising 80-95% maltitol and 0.5-3% peppermint oil (based on total coating mass), and
a coating-plastifying substance selected from the group consisting of glycerol, polyethylene glycol, propylene glycol, povidone (polyvinyl pyrrolidone), copovidone (vinyl pyrrolidone vinyl acetate copolymer), hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, diethyl phthalate, dibutyl phthalate, diacetin, triacetin, triethyl citrate, dibutyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, 2 pyrrolidone and any mixtures thereof.

15. A chewing gum according to claim 14 , wherein the coating-plastifying substance is glycerol.

16. A stable chewing gum for use in nicotine replacement therapy comprising a coated core, the core comprising
a compressible chewing gum base suitable for tableting at ambient temperature, at least,
one nicotine active selected from the group consisting of pharmaceutically acceptable,
salts of nicotine and pharmaceutically acceptable, cellulose-free, nicotine complexes,
and resins, and
at least one buffering agent in homogeneous mixture with the nicotine active, said at least one buffering agent comprising particles comprising a core of sodium bicarbonate and an outer layer of sodium carbonate,
whereby the core is tableted, and
a coating which is optionally free of nicotine active.

17. A chewing gum according to claim 16 , comprising the at least one nicotine active in an amount corresponding to from 0.2 to 8 mg of nicotine free base.

18. A chewing gum according to claim 17 , comprising nicotine bitartrate as the nicotine active.

19. A chewing gum according to claim 16 , wherein the coating comprises maltitol.

20. A chewing gum according to claim 19 , wherein the coating comprises maltitol in an amount of 80-95% of the total coating mass and peppermint oil in an amount of 0.5-3% of the total coating mass.

21. A chewing gum according to claim 19 , wherein the coating comprises a binder selected from the group consisting of arabic gum, tragacanth gum, guar gum, acacia gum, xanthan gum, alginic acid, salts of alginic acid, gellan gum, glucomannan gum, carrageenan gum, karaya gum, locust bean gum, tara gum, gelatin and any mixtures thereof.

22. A chewing gum according to claim 21 , wherein the coating comprises a coating-plastifying substance selected from the group consisting of glycerol, polyethylene glycol, propylene glycol, povidone (polyvinyl pyrrolidone), copovidone (vinyl pyrrolidone vinyl acetate copolymer) , hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, diethyl phthalate, dibutyl phthalate, diacetin, triacetin, triethyl citrate, dibutyl citrate, acetyl tributyl citrate, acetyl triethyl citrate, 2 pyrrolidone and any mixtures thereof.

23. A chewing gum according to claim 22 wherein the coating-plastifying substance comprises glycerol.

24. A chewing gum according to claim 16 having , wherein fast-but non-toxic, pharmaceutically acceptable - buccal absorption of nicotine means reaching a mean plasma concentration C (5 min) of from 1 up to 6 ng/ml.

Assignees

• Rudolph Markus
• Marzano Giovanna
• Rault Isabelle
• Novartis Ag

Inventors

• Rudolph Markus
• Marzano Giovanna
• Rault Isabelle

Classifications

• A61P25/34

  Tobacco-abuse · CPC title

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K31/465 Primary

  Nicotine; Derivatives thereof · CPC title

• A61K9/0058 Primary

  Chewing gums (non-medicinal aspects, preparing chewing gum A23G4/00; chewing gum for care of the teeth or oral cavity, e.g. with breath freshener A61Q11/00) · CPC title

• A61K47/46

  Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts · CPC title