Phenylephrine liquid formulations

• US 20070197661A1
• Filed: 02/09/2007
• Published: 08/23/2007
• Est. Priority Date: 02/21/2006
• Status: Active Grant

• Current Assignee: Haleon US Holdings LLC (Haleon Plc)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Bubnis, William, Shield, Stephanie, Alley, Amanda
• Granted Patent: US 8,940,796 B2
• Time in Patent Office: Days
• US Class Current: 514/646
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/26 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 Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00

Abstract

An oral, aqueous-based, liquid pharmaceutical composition is provided. The composition comprises up to about 45% w/v glycerin and up to about 10% w/v sorbitol wherein the glycerin to sorbitol ratio is about 2:1 to 10:1.

Claims

1. An aqueous oral pharmaceutical composition comprising:

a). Phenylephrine;

b). artificial sweetener;

c). up to about 45% w/v glycerin; and

d). up to about 10% w/v sorbitol wherein the glycerin to sorbitol ratio is about 2;

1 to about 10;

1.

2. The composition of claim 1, wherein the glycerin to sorbitol ratio is about 2:

1 to about 5;

1.

3. The composition of claim 1, wherein the artificial sweetener is selected from the group consisting of sucralose, saccharine salts, cyclamates, acesulfame K, dipeptide based sweeteners, aspartame and mixtures thereof.

4. The composition of claim 3, where in the artificial sweetener comprises sucralose.

5. The composition of claim 1, further comprising a flavor system.

6. The composition of claim 5, wherein the flavor system includes non-aldehyde flavorants.

7. The composition of claim 1, further comprising at least one second active agent selected from the group consisting of analgesics, decongestants, expectorants, anti-tussives, antipyretics, anti-inflammatory agents, cough suppressants and antihistamines.

8. The composition of claim 7, wherein the second active agent is selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDS), propionic acid derivatives, ibuprofen, naproxen, ketoprofen, flurbiprofen, fenoprofen, suprofen, fluprofen, fenbufen;

acetic acid derivatives, tolmetin sodium, zomepirac, sulindac, indomethacin, fenamic acid derivatives, mefenamic acid meclofenamate sodium, biphenyl carboxylic acid derivatives, diflunisal, flufenisal, oxicams, piroxicam, sudoxicam, isoxicam, chlorpheniramine, brompheniramine;

dexchlorpheniramine, dexbrompheniramine, triprolidine, chlorcyclizine, diphenhydramine, doxylamine, tripelenamine, cyproheptatine, bromodiphenhydramine, phenindamine, pyrilamine, azatadine, acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, carbinoxamine, desloratadine, loratadine, pheniramine, thonzylamine, mizolastine, terfenadine, chlophendianol, caramiphen, dextromethorphan, diphenhydramine, codeine, hydrocodone, pseudoephedrine, ephedrine, phenylephrine, phenylpropenolamine, terpin hydrate, guaifenesin, potassium, potassium guaicolsulfonate, Cox 2 inhibitors, Celecoxib, Rofecoxib, Valdecoxib, aspirin, acetaminophen, phenacetin, salicylate salts and combination thereof.

9. The composition of claim 7, wherein the at least one second active agent is selected from the group consisting of chlorpheniramine, dextromethorphan, guaifenesin, acetaminophen, chlophendianol, diphenhydramine, brompheniramine, loratadine, aspirin and doxylamine succinate.

10. The composition of claim 1, wherein the composition is an aqueous based solution.

11. The composition of claim 1, further comprising a buffering agent.

12. The composition of claim 11, wherein the buffering agent maintains a pH below about 5.4 in the composition.

13. The composition of claim 11, wherein the buffering agent maintains a pH between about 2 and about 4.5 in the composition.

14. The composition of claim 1, further comprising a preservative.

15. The composition of claim 14, wherein the preservative is selected from the group consisting of sodium benzoate, sorbates, parabens, EDTA and combinations thereof.

16. The composition of claim 1, further comprising an antioxidant.

17. The composition of claim 16, wherein the antioxidant is propyl gallate.

18. An aqueous pharmaceutical solution comprising:

a). phenylephrine;

b). artificial sweetener;

c). about 18% to about 30% w/v glycerin; and

d). about 3% to about 10% w/v sorbitol, wherein the glycerin to sorbitol ratio is about 2;

1 to about 10;

1.

19. The solution of claim 18, wherein the glycerin to sorbitol ratio is about 2:

1 to about 5;

1.

20. The solution of claim 18, wherein the artificial sweetener is selected from the group consisting of sucralose, saccharine salts, cyclamates, acesulfame K, dipeptide based sweeteners, aspartame and mixtures thereof.

21. The solution of claim 20, wherein the artificial sweetener comprises sucralose.

22. The solution of claim 18, further comprising an effective amount of at least one second active agent selected from the group consisting of analgesics, decongestants, expectorants, anti-tussives, antipyretics, anti-inflammatory agents, cough suppressants and antihistamines.

23. The solution of claim 22, wherein the second active agent is selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDS), propionic acid derivatives, ibuprofen, naproxen, ketoprofen, flurbiprofen, fenoprofen, suprofen, fluprofen, fenbufen;

acetic acid derivatives, tolmetin sodium, zomepirac, sulindac, indomethacin, fenamic acid derivatives, mefenamic acid meclofenamate sodium, biphenyl carboxylic acid derivatives, diflunisal, flufenisal, oxicams, piroxicam, sudoxicam, isoxicam, chlorpheniramine, brompheniramine;

dexchlorpheniramine, dexbrompheniramine, triprolidine, chlorcyclizine, diphenhydramine, doxylamine, tripelenamine, cyproheptatine, bromodiphenhydramine, phenindamine, pyrilamine, azatadine, acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, carbinoxamine, desloratadine, loratadine, pheniramine, thonzylamine, mizolastine, terfenadine, chlophendianol, caramiphen, dextromethorphan, diphenhydramine, codeine, hydrocodone, pseudoephedrine, ephedrine, phenylephrine, phenylpropenolamine, terpin hydrate, guaifenesin, potassium, potassium guaicolsulfonate, Cox 2 inhibitors, Celecoxib, Rofecoxib, Valdecoxib, aspirin, acetaminophen, phenacetin, salicylate salts and combination thereof.

24. The solution of claim 23, wherein the at least one second active agent is selected from the group consisting of chlorpheniramine, dextromethorphan, guaifenesin, acetaminophen, chlophendianol, diphenhydramine brompheniramine, loratadine, aspirin and doxylamine succinate.

25. The solution of claim 18, further comprising up to about 1.25% w/v citric acid.

26. The solution of claim 18, further comprising up to about 0.2% w/v propyl gallate.

27. An aqueous oral pharmaceutical suspension composition comprising:

a). phenylephrine,

b). artificial sweetener,

c) a viscosity modifying agent,

c). up to about 45% w/v glycerin, and

d). up to about 10% w/v sorbitol wherein the glycerin to sorbitol ratio is about 2;

1 to about 10;

1.

28. The suspension of claim 27, wherein the viscosity modifying agent is selected from the group consisting of chitosen, microcrystalline cellulose, xanthan, HPMC, HPC, HEC, galaotomannons and combinations thereof.

29. The suspension of claim 27, wherein the artificial sweetener is selected from the group consisting of sucralose, saccharine salts, cyclamates, acesulfame K, dipeptide based sweeteners, aspartame and mixtures thereof.

30. The suspension of claim 27, wherein the artificial sweetener comprises sucralose.

31. The suspension of claim 27, further comprising an effective amount of at least a second active agent selected from the group consisting of analgesics, decongestants, expectorants, anti-tussives, antipyretics, anti-inflammatory agents, cough suppressants and antihistamines.

32. The suspension of claim 31, wherein the second active agent is selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDS), propionic acid derivatives, ibuprofen, naproxen, ketoprofen, flurbiprofen, fenoprofen, suprofen, fluprofen, fenbufen;

acetic acid derivatives, tolmetin sodium, zomepirac, sulindac, indomethacin, fenamic acid derivatives, mefenamic acid meclofenamate sodium, biphenyl carboxylic acid derivatives, diflunisal, flufenisal, oxicams, piroxicam, sudoxicam, isoxicam, chlorpheniramine, brompheniramine;

dexchlorpheniramine, dexbrompheniramine, triprolidine, chlorcyclizine, diphenhydramine, doxylamine, tripelenamine, cyproheptatine, bromodiphenhydramine, phenindamine, pyrilamine, azatadine, acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, carbinoxamine, desloratadine, loratadine, pheniramine, thonzylamine, mizolastine, terfenadine, chlophendianol, caramiphen, dextromethorphan, diphenhydramine, codeine, hydrocodone, pseudoephedrine, ephedrine, phenylephrine, phenylpropenolamine, terpin hydrate, guaifenesin, potassium, potassium guaicolsulfonate, Cox 2 inhibitors, Celecoxib, Rofecoxib, Valdecoxib, aspirin, acetaminophen, phenacetin, salicylate salts and combination thereof.

33. The suspension of claim 32, wherein the second active agent is selected from the group consisting of chlorpheniramine, dextromethorphan, guaifenesin, acetaminophen, chlorphendianol, doxylamine succinate and ibuprofen.

34. A method of treating an mammal in need of treatment comprising providing an effective amount of an aqueous oral pharmaceutical composition comprising phenylephrine, artificial sweetener, up to about 45% glycerin, and up to about 10% sorbitol, wherein the glycerin to sorbitol ratio is about 2:

1 to about 10;

1.

35. The method of claim 34, wherein the pharmaceutical composition further comprises at least one second active agent.

36. The method of claim 35, wherein the second active agent is selected from the group consisting of analgesics, decongestants, expectorants, anti-tussives, antipyretics, anti-inflammatory agents, cough suppressants and antihistamines.

37. An aqueous oral pharmaceutical composition comprising:

a). an active agent selected from the group consisting of analgesics, decongestants, expectorants, anti-tussives, antipyretics, anti-inflammatory agents, cough suppressants, antihistamines and mixtures thereof;

b). artificial sweetener;

c). up to about 45% w/v glycerin; and

d). up to about 10% w/v sorbitol wherein the glycerin to sorbitol ratio is about 2;

1 to about 10;

1.

38. The composition of claim 37, wherein the active agent is selected from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDS), propionic acid derivatives, ibuprofen, naproxen, ketoprofen, flurbiprofen, fenoprofen, suprofen, fluprofen, fenbufen;

acetic acid derivatives, tolmetin sodium, zomepirac, sulindac, indomethacin, fenamic acid derivatives, mefenamic acid meclofenamate sodium, biphenyl carboxylic acid derivatives, diflunisal, flufenisal, oxicams, piroxicam, sudoxicam, isoxicam, chlorpheniramine, brompheniramine;

dexchlorpheniramine, dexbrompheniramine, triprolidine, chlorcyclizine, diphenhydramine, doxylamine, tripelenamine, cyproheptatine, bromodiphenhydramine, phenindamine, pyrilamine, azatadine, acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, carbinoxamine, desloratadine, loratadine, pheniramine, thonzylamine, mizolastine, terfenadine, chlophendianol, caramiphen, dextromethorphan, diphenhydramine, codeine, hydrocodone, pseudoephedrine, ephedrine, phenylephrine, phenylpropenolamine, terpin hydrate, guaifenesin, potassium, potassium guaicolsulfonate, Cox 2 inhibitors, Celecoxib, Rofecoxib, Valdecoxib, aspirin, acetaminophen, phenacetin, salicylate salts and combination thereof.

39. The composition of claim 38, wherein the active agent is selected from the group consisting of chlorpheniramine, dextromethorphan, guaifenesin, acetaminophen, chlophendianol, diphenhydramine, brompheniramine, loratadine, aspirin, doxylamine succinate and combinations thereof.

40. The composition of claim 39, further comprising an antioxidant.

41. The composition of claim 40, wherein the antioxidant is propyl gallate.