TANNATE DRY POWDER FORMULATIONS

• US 20120022009A1
• Filed: 07/20/2011
• Published: 01/26/2012
• Est. Priority Date: 07/21/2010
• Status: Abandoned Application

• Current Assignee: Acella Pharmaceuticals LLC (Acella Pharmaceuticals)
• Original Assignee: Acella Pharmaceuticals LLC (Acella Pharmaceuticals)
• Inventors: Bryant, Thomas Jeffrey
• Application Number:
  US13/186,669
• Publication Number:
  US 20120022009A1
• Time in Patent Office: Days
• US Class Current: 514/25
• CPC Class Codes: A61K 31/7028 Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

Dry powder tannate compositions containing bioactive agents, tannic acid, dispersants, and viscosity modifying agents are disclosed. Specifically, the bioactive agents are antihistamines, decongestants, antitussives, and anticholinergics. The dry powder formulations can further include pharmaceutically acceptable excipients. The dry powder formulations exhibit increased stability for extended shelf life. Bioactive agent tannate salts remain suspended for at least two weeks following formation of the suspension in a pharmaceutically acceptable aqueous liquid.

Claims

1. A dry powder formulation comprising one or more bioactive agents, tannic acid, a high molecular weight polymeric dispersant, and a viscosity modifying agent,

wherein the dry powder formulation is stable for at least two weeks at 25°

C. and 60% relative humidity.

2. A suspension formulation formed from the dry powder formulation of claim 1 and a pharmaceutically acceptable aqueous liquid,

wherein the suspension is stable for at least two weeks following suspension at 25°

C. and 60% relative humidity.

3. The formulation of claim 1, wherein the bioactive agent is selected from the group consisting of antihistamines, decongestants, antitussives, anticholinergics, and combinations thereof.

4. The formulation of claim 2, wherein the bioactive agent is selected from the group consisting of antihistamines, decongestants, antitussives, anticholinergics, and combinations thereof.

5. The formulation of claim 3, wherein the antihistamine is present in an amount from about 0.05% to about 5.00% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

6. The formulation of claim 4, wherein the antihistamine is present in an amount from about 0.20% to about 5.00% w/v (% weight/volume) of the suspension.

7. The formulation of claim 5, wherein the antihistamine is present in about 0.12% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

8. The formulation of claim 6, wherein the antihistamine is present in about 0.12% w/v (% weight/volume) of the suspension.

9. The formulation of claim 3 wherein the antihistamine is selected from the group consisting of brompheniramine, chlorpheniramine, dexbrompheniramine, dexchlorpheniramine, carbinoxamine, clemastine, diphenhydramine, pyrilamine, tripelennamine, tripolidine, methdilazine, bromodiphenhydramine, promethazine, azatadine, cyproheptadine, diphenylpyraline, doxylamine, trimeprazine, phenindamine, hydroxyzine, ketotifen, tazifylline, meclazine, setastine, oxatomide, levocarbastine, lodoxamide, pheniramine, propiomazine, emedastine, flunarizine, meclozine, mefenidramine, methylsulfate, mepyramine, combinations thereof, and pharmaceutically acceptable salts thereof.

10. The formulation of claim 4 wherein the antihistamine is selected from the group consisting of brompheniramine, chlorpheniramine, dexbrompheniramine, dexchlorpheniramine, carbinoxamine, clemastine, diphenhydramine, pyrilamine, tripelennamine, tripolidine, methdilazine, bromodiphenhydramine, promethazine, azatadine, cyproheptadine, diphenylpyraline, doxylamine, trimeprazine, phenindamine, hydroxyzine, ketotifen, tazifylline, meclazine, setastine, oxatomide, levocarbastine, lodoxamide, pheniramine, propiomazine, emedastine, flunarizine, meclozine, mefenidramine, methylsulfate, mepyramine, combinations thereof, and pharmaceutically acceptable salts thereof.

11. The formulation of claim 3, wherein the antihistamine is selected from the group consisting of fexofenadine, loratadine, descarboethoxyloratadine, norastemizole, desmethylastemizole, cetirizine, acrivastine, ketotifen, temelastine, ebastine, epinastine, mizolastine, and setastine, astemizole, levocetirizine, rupatadine, mizolastin, noberastine, mequitazine, combinations thereof, and pharmaceutically acceptable salts thereof.

12. The formulation of claim 4, wherein the antihistamine is selected from the group consisting of fexofenadine, loratadine, descarboethoxyloratadine, norastemizole, desmethylastemizole, cetirizine, acrivastine, ketotifen, temelastine, ebastine, epinastine, mizolastine, and setastine, astemizole, levocetirizine, rupatadine, mizolastin, noberastine, mequitazine, combinations thereof, and pharmaceutically acceptable salts thereof.

13. The formulation of claim 11, wherein the antihistamine is chlorpheniramine maleate.

14. The formulation of claim 12, wherein the antihistamine is chlorpheniramine maleate.

15. The formulation of claim 3, wherein the decongestant is present in an amount from about 0.10% to about 5.00% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

16. The formulation of claim 4, wherein the decongestant is present in an amount from about 0.10% to about 5.00% w/v (% weight/volume) of the suspension.

17. The formulation of claim 15, wherein the decongestant is present at a concentration of about 0.20% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

18. The formulation of claim 16, wherein the decongestant is present at a concentration of about 0.20% w/v (% weight/volume) of the suspension.

19. The formulation of claim 15, wherein the decongestant is selected from the group consisting of phenylephedrine, pseudoephedrine, levo-methamphetamine, naphazoline, oxymetazoline, phenylpropanolamine, propylhexedrine, synephrine tetrahydrozoline, cyclopentamine, epinephrine, fenoxazoline, levonordefrin, mephentermine, metizoline, norepinephrine, tramazoline, tuaminoheptane, tymazoline, combinations thereof, and pharmaceutically acceptable salts thereof.

20. The formulation of claim 16, wherein the decongestant is selected from the group consisting of phenylephedrine, pseudoephedrine, levo-methamphetamine, naphazoline, oxymetazoline, phenylpropanolamine, propylhexedrine, synephrine tetrahydrozoline, cyclopentamine, epinephrine, fenoxazoline, levonordefrin, mephentermine, metizoline, norepinephrine, tramazoline, tuaminoheptane, tymazoline, combinations thereof, and pharmaceutically acceptable salts thereof.

21. The formulation of claim 19, wherein the decongestant is phenylephrine hydrochloride.

22. The formulation of claim 20, wherein the decongestant is phenylephrine hydrochloride.

23. The formulation of claim 3, wherein the antitussive is present in an amount from about 0.25% to about 5.00% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

24. The formulation of claim 4, wherein the antitussive is present in an amount from about 0.25% to about 5.00% w/v (% weight/volume) of the suspension.

25. The formulation of claim 23, wherein the antitussive is present in about 0.3% w/v (% weight/volume), upon suspension in a pharmaceutically acceptable aqueous liquid.

26. The formulation of claim 24, wherein the antitussive is present in about 0.3% w/v (% weight/volume) of the suspension.

27. The formulation of claim 23, wherein the formulation comprises an antitussive selected from the group consisting of carbetapentane, dextromethorphan, codeine, hydrocodone, oxycodone, morphine, combinations thereof, and pharmaceutically acceptable salts thereof.

28. The formulation of claim 24, wherein the formulation comprises an antitussive selected from the group consisting of carbetapentane, dextromethorphan, codeine, hydrocodone, oxycodone, morphine, combinations thereof, and pharmaceutically acceptable salts thereof.

29. The formulation of claim 27, wherein the antitussive is dextromethorphan hydrobromide.

30. The formulation of claim 28, wherein the antitussive is dextromethorphan hydrobromide.

31. The formulation of claim 3, wherein the anticholinergic is present in an amount from about 0.01% to about 0.3% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

32. The formulation of claim 4, wherein the anticholinergic is present in an amount from about 0.01% to about 0.3% w/v (% weight/volume) of the suspension.

33. The formulation of claim 31, wherein the anticholinergic is present in an amount of about 1.50% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

34. The formulation of claim 32, wherein the anticholinergic is present in an amount of about 1.50% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

35. The formulation of claim 31, wherein the formulation comprises an anticholinergic selected from the group consisting of atropine, scopolamine, homatropine, atropine, methscopolamine, hyoscyamine, methylatropine, ipratropium, methylecgonidine (MEG), mecamylamine, benactyzine, benztropine, trihexyphenidyl, biperiden, procyclidine, benzetimide, dexetimide, dicycloverine, tolterodine, oxybutynin, pirenzepine, telenzepine, tiotropium, clidinium, combinations thereof, and pharmaceutically acceptable salts thereof.

36. The formulation of claim 32, wherein the formulation comprises an anticholinergic selected from the group consisting of atropine, scopolamine, homatropine, atropine, methscopolamine, methylatropine, hyoscyamine, ipratropium, methylecgonidine (MEG), mecamylamine, benactyzine, benztropine, trihexyphenidyl, biperiden, procyclidine, benzetimide, dexetimide, dicycloverine, tolterodine, oxybutynin, pirenzepine, telenzepine, tiotropium, clidinium, combinations thereof, and pharmaceutically acceptable salts thereof.

37. The formulation of claim 35, wherein the anticholinergic is methscopolamine nitrate.

38. The formulation of claim 36, wherein the anticholinergic is methscopolamine nitrate.

39. The formulation of claim 1, wherein the concentration of tannic acid is from about 0.3% to about 5.00% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

40. The formulation of claim 2, wherein the concentration of tannic acid is from about 0.3% to about 5.00% w/v (% weight/volume) of the suspension.

41. The formulation of claim 1, wherein the dispersant is present in an amount from about 0.50% to about 10.0% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

42. The formulation of claim 2, wherein the dispersant is present in an amount from about 0.50% to about 10.0% w/v (% weight/volume) of the suspension.

43. The formulation of claim 41, wherein the dispersant is present in an amount from about 0.50% to 3.0%.

44. The formulation of claim 42, wherein the dispersant is present in an amount from about 0.50% to 3.0%.

45. The formulation of claim 1, wherein the dispersant is carrageenan or maltodextrin.

46. The formulation of claim 1, wherein the viscosity modifying agent is present in an amount from about 0.50% to about 10.0% w/v (% weight/volume) upon suspension in a pharmaceutically acceptable aqueous liquid.

47. The formulation of claim 2, wherein the viscosity modifying agent is present in an amount from about 0.50% to about 10.0% w/v (% weight/volume) of the suspension.

48. The formulation of claim 46, wherein the viscosity modifying agent is present in an amount from about 0.5% to about 2.0% w/v (% weight/volume).

49. The formulation of claim 47, wherein the viscosity modifying agent is present in an amount from about 0.5% to about 2.0% w/v (% weight/volume).

50. The formulation of claim 1, wherein the viscosity modifying agent is propylene glycol alginate.

51. The formulation of claim 1 further comprising dry powder excipients selected from the group consisting of diluents, binders, lubricants, disintegrators, fillers, plasticizers, pigments, colorants, stabilizing agents, glidants, surfactants, humectants, plasticizers, crystallization inhibitors, wetting agents, bulk filling agents, solubilizers, bioavailability enhancers, pH adjusting agents, and combinations thereof.

52. The formulation of claim 2 further comprising dry powder excipients selected from the group consisting of diluents, binders, lubricants, disintegrators, fillers, plasticizers, pigments, colorants, stabilizing agents, glidants, surfactants, humectants, plasticizers, crystallization inhibitors, wetting agents, bulk filling agents, solubilizers, bioavailability enhancers, pH adjusting agents, and combinations thereof.

53. The formulation of claim 2, wherein the viscosity of the suspension is between about 2000 cPs and about 4000 cPs.

54. The formulation of claim 1, wherein the one or more bioactive agents present in the dry powder formulation degrades less than about 5%, as determined by high performance liquid chromatography, for at least two weeks at 25°

C. and 60% relative humidity for at least 36 months.

55. The formulation of claim 2, wherein the one or more bioactive agents present in the suspension formulation degrades less than about 5%, as determined by high performance liquid chromatography, for at least two weeks at 25°

C. and 60% relative humidity for at least 16 months.

57. A method for the preparation of a stable suspension of the dry powder formulation of claim 51, further comprising:

(c) the addition of a pharmaceutically acceptable aqueous liquid to the container,

wherein the one or more bioactive agents present in the suspension formulation degrades less than about 5%, as measured by high performance liquid chromatography, for at least two weeks at 25°

C. and 60% relative humidity.

58. The formulation of claim 2, wherein ratio of the dispersant and viscosity modifying agent is about 3.0% dispersant (% w/v) to about 2.0% (% w/v) viscosity modifying agent.

56. A method for the preparation of stable dry powder formulations, comprising:

(a) mixing one or more bioactive agents, tannic acid, a high molecular weight polymeric dispersant, and a viscosity modifying agent, all in their non-reactive dry powder forms, with a low shear blender until uniformly mixed, and

(b) filling a container with the dry powder,

wherein the one or more bioactive agents present in the dry powder formulation degrades less than about 5%, as determined by high performance liquid chromatography, for at least two weeks at 25°

C. and 60% relative humidity.