Enhanced stability phenylephrine liquid compositions

• US 20080014274A1
• Filed: 07/14/2006
• Published: 01/17/2008
• Est. Priority Date: 07/14/2006
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Shield, Stephanie, Hoskovec, Gayle P., Bubnis, William
• Application Number:
  US11/487,120
• Publication Number:
  US 20080014274A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• 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: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 29/02 without antiinflammatory effect
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

An oral, liquid pharmaceutical composition is provided. The composition comprises phenylephrine and substantially aldehyde-free polyethylene glycol. The composition has phenylephrine stability compatible with the stability required for commercial preparations. Optionally, the composition may comprise one or more additional active agents.

Claims

1. An oral liquid pharmaceutical composition comprising:

a). phenylephrine; and

b). substantially aldehyde-free polyethylene glycol, wherein the substantially aldehyde-free polyethylene glycol has less than 20 ppm total aldehyde content and maintains said level of aldehyde content for at least six months.

2. The composition of claim 1, wherein the substantially aldehyde-free polyethylene glycol has less than 10 ppm total aldehyde content and maintains said level of aldehyde content for at least one year.

3. 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.

4. The composition of claim 3, 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, zomepirac, sulindac fenoprofen, suprofen, fluprofen, fenbufen;

acetic acid derivatives, tolmetin sodium, 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.

5. The composition of claim 4, 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.

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

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

8. The composition of claim 1, wherein the composition is an aqueous based solution, aqueous based suspension, or liquid fill for a capsule.

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

10. The composition of claim 9, wherein the antioxidant is propyl gallate.

11. A method of treating an mammal in need of treatment comprising providing an effective amount of oral liquid pharmaceutical composition of claim 1.

12. An aqueous oral pharmaceutical composition comprising:

a). phenylephrine;

b). substantially aldehyde-free polyethylene glycol, wherein the substantially aldehyde-free polyethylene glycol has less than 20 ppm total aldehyde content and maintains said level of aldehyde content for at least six months;

c). artificial sweetener;

d). up to about 45% glycerin; and

e). up to about 50% sorbitol.

13. The composition of claim 12, wherein the substantially aldehyde-free polyethylene glycol has less than 10 ppm total aldehyde content and maintains said level of aldehyde content for at least one year.

14. The composition of claim 12, wherein the artificial sweetener is selected from the group consisting of sucralose, saccharine salts, cyclamates, acesulfame K, dipeptide based sweeteners, aspartame and mixtures thereof.

15. The composition of claim 14, where in the artificial sweetener comprises sucralose.

16. The composition of claim 12, further comprising a flavor system.

17. The composition of claim 16, wherein the flavor system includes non-aldehyde flavorants.

18. The composition of claim 12, 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.

19. The composition of claim 18, wherein the second active agent is selected propionic acid derivatives, ibuprofen, naproxen, ketoprofen, flurbiprofen, fenoprofen, from the group consisting of non-steroidal anti-inflammatory drugs (NSAIDS), 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.

20. The composition of claim 19, 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.

21. The composition of claim 12, wherein the composition is an aqueous based solution.

22. The composition of claim 12, further comprising an antioxidant.

23. The composition of claim 22, wherein the antioxidant is propyl gallate.

24. The composition of claim 12, further comprising a buffering agent.25.

25. The composition of claim 24, wherein the buffering agent maintains a pH below 5.4 in the composition.

26. The composition of claim 25, wherein the buffering agent maintains a pH between about 2 and about 5 in the composition.

27. The composition of claim 12, further comprising a preservative.

28. The composition of claim 27, wherein the preservative is selected from the group consisting of sodium benzoate, sorbates, parabens, EDTA and combinations thereof.

37. A method of treating an mammal in need of treatment comprising providing an effective amount of an aqueous oral pharmaceutical composition of claims 12 or 29.

38. The method of claim 37, wherein the pharmaceutical composition further comprises at least one second active agent.

39. The method of claim 38, 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.

29. An aqueous oral pharmaceutical composition comprising:

a). phenylephrine;

b). substantially aldehyde-free polyethylene glycol, wherein the substantially aldehyde-free polyethylene glycol has less than 20 ppm total aldehyde content and maintains said level of aldehyde content for at least six months;

c). an artificial sweetener;

d a viscosity modifying agent;

e). up to about 45% glycerin; and

f). up to about 50% sorbitol.

30. The composition of claim 29, wherein the substantially aldehyde-free polyethylene glycol has less than 10 ppm total aldehyde content and maintains said level of aldehyde content for at least one year.

31. The composition of claim 29, wherein the viscosity modifying agent is selected from the group consisting of chitosen, microcrystalline cellulose, xanthan, HPMC, HPC, HEC, galaotomannons and combinations thereof.

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

33. The composition of claim 29, wherein the artificial sweetener comprises sucralose.

34. The composition of claim 29, 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.

35. The composition of claim 34, 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, 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.

36. The composition of claim 35, wherein the second active agent is selected from the group consisting of chlorpheniramine, dextromethorphan, guaifenesin, acetaminophen, chlorphendianol, doxylamine succinate and ibuprofen.