All Day Rhinitic Condition Treatment Regimen

• US 20080311196A1
• Filed: 06/12/2008
• Published: 12/18/2008
• Est. Priority Date: 07/13/2006
• Status: Abandoned Application

• Current Assignee: Cornerstone Biopharma Incorporated (Valline Srl)
• Original Assignee: Cornerstone Biopharma Incorporated (Valline Srl)
• Inventors: White, Donna F.
• Application Number:
  US12/138,381
• Publication Number:
  US 20080311196A1
• Time in Patent Office: Days
• US Class Current: 424/465
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/435 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants

Abstract

A therapeutic regimen is disclosed. The regimen includes a first pharmaceutical dosage form comprising a first therapeutically effective amount of a first antihistamine and an anticholinergic agent; and a second pharmaceutical dosage form comprising a therapeutically effective amount of a second antihistamine and an anticholinergic agent. The second antihistamine either has greater H₁ receptor activity or greater sedative effect than the first antihistamine, or is a different dose of the same antihistamine. The regimen comprises indicia for distinguishing between the first and second pharmaceutical dosage forms, wherein one dosage form is for daytime administration and the other is for nighttime administration. The regimen is placed in a prepackaged dispenser prefilled with the pharmaceutical dosage forms and comprising the indicia.

Claims

15. A method of formulating a therapeutic regimen for treating rhinitis, comprising:

a) producing a first pharmaceutical dosage form that includes a therapeutically effective amount of a first antihistamine and a therapeutically-effective amount of an anticholinergic agent, and a second pharmaceutical dosage form comprising a therapeutically-effective amount of a second antihistamine, and a therapeutically effective amount of the anticholinergic agent,

wherein the first and second antihistamines are either different antihistamines, or different dosages of the same antihistamine, and wherein one of the first and second dosage forms is a daytime formulation, and the other is a nighttime formulation,

b) providing the dosage forms in packaging that with indicia that distinguishes the daytime formulation from the nighttime formulation, and

c) providing instructions for using the treatment regimen so as to administer the first pharmaceutical dosage form during the day, and the second pharmaceutical dosage form during the evening.

16. The method of claim 15, wherein the daytime and nighttime formulations comprise different dosages of the same antihistamine.

17. The method of claim 15, wherein the daytime and nighttime formulations comprise different antihistamines.

18. The method of claim 15, wherein the daytime formulation comprises a second or third generation antihistamine, and the nighttime formulation comprises a first generation antihistamine.

19. The method of claim 15, wherein the daytime formulation comprises an antihistamine which has less antagonistic activity at the histamine H1 receptor than the antihistamine in the nighttime formulation.

20. The method of claim 15, wherein the daytime formulation comprises a second generation antihistamine, wherein the second or third generation antihistamine is not acrivastine, astemizole, cetirizine, loratadine, mizolastine or fexofenadine.

21. A therapeutic regimen for treating rhinitis, comprising, in a single dosage form:

a) a daytime formulation comprising an anticholinergic agent and an antihistamine, and

b) a nighttime formulation comprising an anticholinergic agent and an antihistamine,

wherein the daytime formulation and nighttime formulation either include different antihistamines, or include different dosages of the same antihistamine, and

wherein the dosage form provides for sustained release, over an initial period, of the daytime formulation, and sustained release, delayed until after the initial period, of the nighttime formulation, or, alternatively, sustained release, over an initial period, of the nighttime formulation, and

sustained release, delayed until after the initial period, of the daytime formulation.

1. A therapeutic regimen for treating rhinitis, comprising:

a) a daytime formulation comprising an anticholinergic agent and a first antihistamine, and

b) a nighttime formulation comprising an anticholinergic agent and a second antihistamine,

wherein the first antihistamine and the second antihistamine are either different antihistamines, or different dosages of the same antihistamine.

2. The therapeutic regimen of claim 1, wherein the daytime formulation comprises a second or third generation antihistamine, and the nighttime formulation comprises a first generation antihistamine.

3. The therapeutic regimen of claim 1, wherein the daytime formulation and the nighttime formulation both comprise a first generation antihistamine, wherein the dosage of the antihistamine in the daytime formulation is attenuated to lower the amount of sedation relative to the nighttime formulation.

4. The therapeutic regimen of claim 1, wherein the daytime formulation and the nighttime formulation both comprise a first generation antihistamine, wherein the daytime formulation further comprises a decongestant which lowers the amount of sedation relative to the nighttime formulation.

5. The therapeutic regimen of claim 4, wherein the amount of the decongestant is sufficient to lower the amount of sedation relative to the nighttime formulation, and is provided in an amount suitable to cause the overall formulation to not be stimulating for the majority of patients.

6. The therapeutic regimen of claim 1, wherein the formulation is substantially devoid of a decongestant.

7. The therapeutic regimen of claim 1, wherein the antihistamine in the nighttime formulation is chlorpheniramine maleate.

8. The therapeutic regimen of claim 1, wherein the anticholinergic agent is methscopolamine.

9. The therapeutic regimen of claim 1, wherein the antihistamine in the daytime formulation is not acrivastine, astemizole, cetirizine, loratadine, mizolastine or fexofenadine.

10. The therapeutic regimen of claim 1, wherein the first antihistamine has less antagonistic activity at the histamine H1 receptor than the second antihistamine.

11. The therapeutic regimen of claim 1, further comprising indicia for distinguishing between the daytime and nighttime formulations.

12. The therapeutic regimen of claim 1, further comprising packaging that separates the daytime from the nighttime formulations.

13. The therapeutic regimen of claim 12, wherein the packaging comprises a blister package.

14. A method of treating rhinitis, comprising administering a formulation of any of claims 1-13 to a patient in need of treatment thereof.

22. The therapeutic regimen of claim 21, wherein the dosage form comprises:

(1) a core including the following active agents;

a) a first antihistamine,

b) an anticholinergic agent, and

c) optionally, a decongestant, and

(2) a swellable polymeric coating layer substantially surrounding the core;

comprising;

a) a second antihistamine and

b) an anticholinergic agent,

wherein the formulation is administered prior to sleep, and wherein the swellable polymeric coating layer delays the release of the pharmaceutically active agents from the core for a predetermined period of time dependent upon the thickness of the swellable polymeric coating layer, to permit delivery of the active agents at about the time of awakening and to treat the symptoms of allergic rhinitis that occur in the early morning,

and wherein the second dosage formulation comprising the second antihistamine is also administered in the evening, and delivers the majority of the second antihistamine during the evening while the patient is asleep.

23. The therapeutic regimen of claim 21, wherein the first and second antihistamines are different antihistamines.

24. The therapeutic regimen of claim 21, wherein the swellable polymeric coating layer comprises a hydrophilic swellable polymer selected from the group consisting of methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic acid polymer, methacrylic acid copolymers, ethyl acrylate-methyl methacrylate copolymers, natural rubbers, poloxamers, polysaccharides, and mixtures thereof.

25. The therapeutic regimen of claim 21, wherein the swellable polymeric coating layer is applied to the core by film coating.

26. The therapeutic regimen of claim 21, wherein the swellable polymeric coating layer is applied to the core by alternately (i) wetting the core with a binder solution and (ii) coating the core with powdered polymeric coating particles, a sufficient number of times to produce the desired thickness of swellable polymeric coating layer.

27. The therapeutic regimen of claim 26, wherein the binder solution is selected from the group consisting of polyvinylpyrrolidone, hydroxypropylmethylcellulose, polyvinyl alcohol, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, methacrylic acid copolymers, ethyacrylate-methylmethacrylate copolymers, guar gum, arabic gum, xanthan gum, gelatine, pectin and mixtures thereof;

and the powdered polymeric coating particles comprise a hydrophilic swellable polymer selected from the group consisting of methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, polyvinyolpyrrolidone, polyvinyl alcohol, acrylic acid polymer, methacrylic acid copolymers, ethyl acrylate-methyl methacrylate copolymers, natural rubbers, poloxamers, polysaccharides, and mixtures thereof.

28. The therapeutic regimen of claim 21, wherein the swellable polymeric coating layer comprises hydroxypropylmethylcellulose.

29. The therapeutic regimen of claim 21, wherein the swellable polymeric coating layer comprises a mixture of 1) hydroxypropylmethylcellose having a typical weight percent substitution corresponding to 29% methoxyl and 8% hydroxypropoxyl groups, and a nominal viscosity of 2% water solution at 20.degree. C. ranging from 3 to 100 mPa·

s; and

     2) hydroxypropylmethylcellulose having a typical weight percent substitution corresponding to 22.1% methoxyl and 8.1% hydroxypropoxyl groups, and a nominal viscosity of 2% water solution at 20.degree. C. ranging from 4,000 to 100,000 mPa·

s.

30. The therapeutic regimen of claim 21, wherein the swellable polymeric coating layer is sufficiently thick to achieve a core:

coating layer weight ratio of between about 20;

1 and about 1;

5.

31. The therapeutic regimen of claim 21, wherein the swellable polymeric coating layer is sufficiently thick to achieve a core:

coating layer weight ratio of between about 5;

1 and about 1;

3.

32. The therapeutic regimen of claim 21, wherein the swellable polymeric coating layer is not less than about 50 μ

m thick.

33. The therapeutic regimen of claim 21, wherein the core further comprises a disintegration enhancing agent.

34. The therapeutic regimen of claim 33, wherein the disintegration enhancing agent is selected from the group consisting of citric acid, tartaric acid, fumaric acid, maleic acid, succinic acid, succinic anhydride, maleic anhydride, sodium dihydrogen phosphate, disodium dihydrogen pyrophosphate, sodium dihydrogen citrate, disodium hydrogen citrate, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, sodium sesquicarbonate, glycine sodium carbonate, calcium carbonate, L-lysine carbonate, and arginine carbonate.

35. The therapeutic regimen of claim 21, wherein the antihistamine to be administered during the daytime comprises a second generation antihistamine, and the antihistamine to be administered during the evening comprises a first generation antihistamine.

36. The therapeutic regimen of claim 21, wherein the antihistamine to be administered during the daytime has less antagonistic activity at the histamine H1 receptor than the antihistamine to be administered in the evening.

37. The therapeutic regimen of claim 21, wherein the daytime formulation comprises a second generation antihistamine, wherein the second generation antihistamine is not acrivastine, astemizole, cetirizine, loratadine, mizolastine or fexofenadine.

38. A method of treating rhinitis, comprising administering a formulation of any of claims 21-37 to a patient in need of treatment thereof.

39. The therapeutic regimen of claim 21, wherein indicia indicating the time of day for administration of the formulation is included.

22-1. The therapeutic regimen of claim 21, wherein the first antihistamine and the second antihistamine are different dosages of the same antihistamine.

40. A method of formulating a therapeutic regimen for treating rhinitis, comprising:

(a) producing in a single dose form,

a daytime formulation comprising an anticholinergic agent and an antihistamine, and, a nighttime formulation comprising an anticholinergic agent and an antihistamine,

wherein the daytime formulation and nighttime formulation either include different antihistamines, or include different dosages of the same antihistamine, and

wherein the dosage form provides for release, over an initial period, of the daytime formulation, and release, delayed until after the initial period, of the nighttime formulation, or, alternatively,

wherein the dosage form provides for release, over an initial period, of the nighttime formulation, and release, delayed until after the initial period, of the daytime formulation.

41. The method of claim 40, wherein the dosage form is provided in a package which comprises indicia indicating the time of day in which the formulation is to be administered.