Pharmaceutical compositions based on chewing gum and a method for the preparation thereof

• US 5,711,961 A
• Filed: 05/29/1996
• Issued: 01/27/1998
• Est. Priority Date: 07/26/1994
• Status: Expired due to Term

• Current Assignee: APR Applied Pharma Research SA (RELIEF THERAPEUTICS Holding SA)
• Original Assignee: APR Applied Pharma Research SA (RELIEF THERAPEUTICS Holding SA)
• Inventors: Reiner, Alberto, Seneci, Alessandro
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FAULKNER, DIEDRA SARRAE
• Application Number:
  US08/619,459
• Time in Patent Office: 608 Days
• Field of Search: 424/440, 424/441, 426/5, 426/3
• US Class Current: 424/441
• CPC Class Codes: A61K 9/0058 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

Abstract

Chewing gum tablets and their methods of preparation are disclosed. The gum tablets contain a mixture of chewing gum base and sugary microgranules with an additive agent and an active ingredient adsorbed onto their surface. A lacquer coating on the tablet contains cellulose and polyethlene glycols. The sugary microgranules are delayed release coated particles. The chewing gums act as vehicles for active ingredients. These active ingredients may be used alone or in combination in normal physical form in the form of coated microspheres.

Claims

1. Chewing gum tablet comprising:

a mixture of a chewing gum base and sugary microgranules;

a component adsorbed onto said sugary microgranules selected from the group consisting of an additive agent and an active ingredient; and

a lacquer coating on the tablet selected from the group consisting of pharmaceutically acceptable celluloses and polyethylene glycols.

2. Chewing gum tablet according to claim 1, wherein said additive agent is a flavoring agent.

3. Chewing gum tablet according to claim 1, wherein said at least one active ingredient is in form of microencapsulated or otherwise delayed release coated particles.

4. Chewing gum tablet according to claim 1, wherein the cellulose is selected are selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetophthalate, carboxymethyl cellulose, hydroxyethyl cellulose, methylhydroxyethyl cellulose and methylhydroxypropyl cellulose phthalate.

5. Chewing gum tablet according to claim 1, wherein the polyethylene glycol is selected from the group consisting of polyethylene glycol 6000 and polyethylene glycol 400.

6. Chewing gum tablet according to claim 1, wherein the lacquer is supplemented with an additional component selected from the group consisting of colorings and dyes.

7. Chewing gum tablet according to claim 2, wherein some said particles of said active ingredient are microencapsulated and some are in free form in a predetermined ratio with regard to the patterns of initial delivery and of maintenance of the blood levels.

8. A method of preparing a tablet, comprising the steps of:

a) freezing chewing gum in pellet form to a temperature of between -20°

C. and -25°

C. to form frozen gum;

b) grinding said frozen gum to a particle size of between 60 and 190 mesh to form ground chewing gum;

c) adding to said ground chewing gum sugary microgranules having adsorbed onto a surface thereof a component selected from the group consisting of an additive agent and au active ingredient to form a granular mixture;

d) compressing said granular mixture to form tablets; and

e) coating said tablets with a lacquer comprising a pharmaceutically acceptable celluloses or a polyethylene glycol in a solvent.

9. A method according to claim 8, wherein said ground chewing gum is mixed with at least one natural or synthetic sweetener in a ratio of 0.3-0.8 parts of gum per 0.6-0.2 parts of sweetener phase.

10. A method according to claim 9, wherein said additive agent is selected from the group consisting of a lubricant and a flavoring agent.

11. A method according to claim 10, wherein said active ingredient is added to the mixture of ground chewing gum, sweetener, lubricant and flavoring agent in the form of microencapsulated or otherwise delayed release coated particles.

12. A method according to claim 8, wherein said solvent is selected from the group consisting of water, an alcohol, acetone, and mixtures thereof.

13. A method according to claim 9, wherein said sweetener is selected from the group consisting of sugars, polyalcohols used as sweeteners, saccharin, acesulfame, aspartame and mixtures thereof.

14. A method according to claim 13, wherein the sugar is selected from the group consisting of dextrose, glucose, sucrose, invert sugar, fructose, mannose and maltose.

15. A method according to claim 13, wherein the polyalcohols are selected from the group consisting of sorbitol, mannitol, maltitol and xylitol.

16. A method according to claim 9, wherein the mixture of gum and sweetener is granulated moist and is dried on a fluid bed.

17. A method according to claim 8, wherein the mixture of said frozen chewing gum pellets and said sugary microgranules is granulated in moistened condition and dried on a fluid bed and then tablets are prepared by compression therefrom.

18. A method according to claim 10, wherein the lubricant is selected from the group consisting of alkali-metal or alkaline-earth metal stearates, stearic acid, hydrogenated vegetable oils and other lubricants used in the preparation of tablets for pharmaceutical use, and is added in an mount of between 0.2% and 2% by weight relative to the weight of the composition.

19. A method according to claim 10, wherein microgranular cellulose and/or precipitated silica are added together with said lubricant.

20. A method according to claim 19, wherein the microgranular cellulose is added in an amount of between 0.1% and 2% by weight.

21. A method according to claim 19, wherein the precipitated silica is added in quantities of between 0.05% and 1% by weight.

22. A method according to claim 8, wherein the flavoring agent is in liquid or powder form.

23. A method according to claim 8, wherein the lacquer is sprayed in a heated vessel with hot air.

24. A chewing gum composition comprising:

a mixture of a chewing gum base and sugary microgranules;

a component adsorbed onto said sugary microgranules selected from the group consisting of an additive agent and an active ingredient; and

a lacquer coating on said microgranules selected from the group consisting of pharmaceutically acceptable cellusoses and polyethylene glycols.

25. Chewing gum composition according to claim 24, wherein said additive agent is a flavoring agent.

26. Chewing gum composition according to claim 24, wherein said at least one active ingredient is in form of microencapsulated or otherwise delayed release coated particles.

27. Chewing gum composition according to claim 24, wherein the cellulose is selected are selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetophthalate, carboxymethyl cellulose, hydroxyethyl cellulose, methylhydroxyethyl cellulose and methylhydroxypropyl cellulose phthalate.

28. Chewing gum composition according to claim 24, wherein the polyethylene glycol is selected from the group consisting of polyethylene glycol 6000 and polyethylene glycol 400.

29. Chewing gum composition according to claim 24, wherein the lacquer is supplemented with an additional component selected from the group consisting of colorings and dyes.

30. Chewing gum tablet according to claim 26, wherein some said particles of said active ingredient are microencapsulated and some are in free form in a predetermined ratio with regard to the patterns of initial delivery and of maintenance of the blood levels.

31. A method of preparing a chewing gum composition, comprising the steps of:

a) providing sugary microgranules having adsorbed onto a surface thereof a component selected from the group consisting of an additive agent and an active ingredient;

b) coating said sugary microgranules with a lacquer comprising a pharmaceutically acceptable celluloses or a polyethylene glycol in a solvent to form coated microgranules;

c) mixing said coated microgranules with frozen ground chewing gum to form a chewing gum composition.

32. A method according to claim 31, wherein said chewing gum is frozen in pellet form to a temperature of between -20°

C. and -25°

C. and ground to a particle size of between 60 and 190 mesh.

33. A method according to claim 31, wherein said ground chewing gum is mixed with at least one natural or synthetic sweetener in a ratio of 0.3-0.8 parts of gum per 0.6-0.2 parts of sweetener phase.

34. A method according to claim 31, wherein said additive agent is selected from the group consisting of a lubricant and a flavoring agent.

35. A method according to claim 31, wherein said active ingredient is in the form of microencapsulated or otherwise delayed release coated particles.

36. A method according to claim 31, wherein said solvent is selected from the group consisting of water, an alcohol, acetone, and mixtures thereof.

37. A method according to claim 33, wherein said sweetener is selected from the group consisting of sugars, polyalcohols used as sweeteners, saccharin, acesulfame, aspartame and mixtures thereof.

38. A method according to claim 37, wherein the sugar is selected from the group consisting of dextrose, glucose, sucrose, invert sugar, fructose, mannose and maltose.

39. A method according to claim 37, wherein the polyalcohols are selected from the group consisting of sorbitol, mannitol, maltitol and xylitol.

40. A method according to claim 34, wherein the lubricant is selected from the group consisting of alkali-metal or alkaline-earth metal stearates, stearic acid, hydrogenated vegetable oils and other lubricants used in the preparation of tablets for pharmaceutical use, and is added in an mount of between 0.2% and 2% by weight relative to the weight of the composition.

41. A method according to claim 34, wherein the flavoring agent is in liquid or powder form.

42. A method according to claim 31, wherein the lacquer is sprayed in a heated vessel with hot air.

43. A method according to claim 31 and further including the step of compressing the chewing gum composition to form a tablet.