Taste masking spill-resistant formulation

• US 20050143471A1
• Filed: 12/09/2004
• Published: 06/30/2005
• Est. Priority Date: 10/22/2001
• Status: Abandoned Application

• Current Assignee: Taro Pharmaceuticals U.S.A., Inc. (Sun Pharmaceutical Industries Limited)
• Original Assignee: Taro Pharmaceuticals U.S.A., Inc. (Sun Pharmaceutical Industries Limited)
• Inventors: Moros, Daniel, Gao, Shen, Moldenhauer, Maxine G.
• Application Number:
  US11/007,903
• Publication Number:
  US 20050143471A1
• Time in Patent Office: Days
• US Class Current: 514/649
• 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 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• 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

Abstract

The invention relates to a spill-resistant pharmaceutical composition, comprising a spill-resistant formulation with taste masking concentrations of polyethylene glycol (PEG) and diphenhydramine, which is less bitter, sweeter and has better overall flavor than current pharmaceutical compositions, while maintaining advantageous spill-resistant properties.

Claims

1. A pharmaceutical composition comprising:

(a) from about 0.1 to about 2.0% (w/w) of diphenhydramine;

(b) from about 0.18 to about 0.60% (w/w) of neutralized carbomer; and

(c) a bitterness masking amount from about 5 to about 30% (w/w) of polyethylene glycol.

2. The composition of claim 1, having a pH greater than about 6.0.

3. The composition of claim 1, comprising less than about 15% polyethylene glycol.

4. The composition of claim 1, having a viscosity greater than about 5,000 cps.

5. The composition of claim 1, having a viscosity from about 7,000 to about 13,000 cps.

6. The composition of claim 1, having mutually compatible components.

7. The composition of claim 1, wherein the composition is free of seaweed polysaccharides.

8. The composition of claim 1, wherein the composition comprises from about 0.1% to about 0.5% (w/w) diphenhydramine.

9. The composition of claim 1, wherein the carbomer is 934 P.

10. The composition of claim 1, wherein the carbomer 934P is from about 0.25% to about 0.60% (w/w).

11. The composition of claim 1, wherein the molecular weight of polyethylene glycol is selected from the group consisting of PEG 600, PEG 800, and PEG 900.

12. The composition of claim 1, wherein the polyethylene glycol is PEG 1000.

13. The composition of claim 1, further comprising up to about 50% (w/w) glycerin.

14. The composition of claim 1, further comprising up to about 2% (w/w) sucralose liquid concentrate.

15. The composition of claim 1, further comprising at least one pharmaceutically acceptable excipient selected from the group consisting of at least one food dye, masking agent, flavoring agent and antimicrobial agent.

16. The composition of claim 1, comprising from about 0.1 to about 0.5% (w/w) of diphenhydramine, from about 0.25 to about 0.60% (w/w) of a neutralized carbomer, from about 5 to about 20% (w/w) polyethylene glycol, up to about 50% (w/w) glycerin, up to about 2% (w/w) sucralose liquid concentrate and water.

17. The composition of claim 1, comprising about 0.219%(w/w) diphenyhdramine, about 0.55% (w/w) neutralized carbomer, about 50% (w/w) glycerin, about 15% (w/w) polyethylene glycol 1000, about 0.2% (w/w) sucralose liquid concentrate, and water.

18. A method comprising administering the composition of claim 1 to a mammal in need of diphenhydramine.

19. An assembly comprising the composition of claim 1 contained in a device for containing and measuring a unit dose of said composition, said device comprising a sealed squeezable container, said container having an outlet, the container comprising an outer flexible squeezable wall which can be squeezed laterally with respect to an axis of said outlet whereby a predetermined unit dose of the pharmaceutical composition can be easily squeezed from the container, measured, and administered orally.

20. A process for preparing a pharmaceutical composition comprising, without regard to order, the steps of:

dispersing carbomer in a liquid to form a first solution;

dissolving diphenhydramine in water to form a second solution;

heating polyethylene glycol to liquid form;

mixing polyethylene glycol into the second solution;

mixing the solution and cooling the mixture to less than 40°

C.; and

titrating the mixture with a sodium hydroxide solution to a final pH of between 6.2 to 8.0.

21. The process of claim 21, wherein the carbomer is dispersed in propylene glycol until a lump free dispersion is formed.

22. The process of claim 21, further comprising mixing butylparaben into the second solution.

23. The process of claim 21, comprising heating the second solution to between about 60°

C. to about 70°

C.

24. The process of claim 21, wherein the pharmaceutical composition comprises about 0.219% (w/w) diphenhydramine, about 0.55% (w/w) carbomer, about 50% (w/w) glycerin, about 15% (w/w) polyethylene glycol 1000, and about 0.2% (w/w) sucralose liquid concentrate.

25. A method of making a taste-masking spill-resistant pharmaceutical composition comprising from about 0.1% to about 0.5% (w/w) diphenhydramine and a spill-resistant base comprising from about 0.18% to about 0.60% (w/w) carbomer and from about 5% to about 30.0% (w/w) polyethylene glycol (PEG), comprising

(a) determining a bitterness masking amount of polyethylene glycol (PEG), and

(b) adding said bitterness masking amount of PEG to the spill-resistant base to form said composition for oral administration.