Pharmaceutical compositions comprising levodopa, a dopamine decarboxylase inhibitor and a COMT inhibitor and method of administration thereof

1. A pharmaceutical composition for intra-intestinal administration, comprising at least about 10 mg/ml of levodopa, at least about 2.5 mg/ml of carbidopa, and at least about 10 mg/ml of entacapone.

2. The pharmaceutical composition of claim 1 , wherein:

the pharmaceutical composition has a pH of about 5.7 or less;

the pharmaceutical composition is deoxygenized;

the pharmaceutical composition further comprises an antioxidant;

the pharmaceutical composition is free from metal chelating agent; and/or

the pharmaceutical composition is provided in a light-protected container.

3. The pharmaceutical composition of claim 1 , wherein the composition has a pH of about 4.5 to about 5.5.

4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises an antioxidant, wherein said antioxidant is ascorbic acid or citric acid.

5. The pharmaceutical composition of claim 1 , wherein the levodopa, the carbidopa, and the entacapone are in the form of particles, wherein the particles are suspended in an aqueous carrier, and have a particle size no greater than 80 μm; and the aqueous carrier has a viscosity of at least 300 mPas at a moderate shear rate.

6. The pharmaceutical composition of claim 5 , wherein the aqueous carrier comprises a polysaccharide selected from the group consisting of cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, salts thereof, and combinations thereof.

7. The pharmaceutical composition of claim 6 , wherein the aqueous carrier comprises sodium carboxymethyl cellulose.

8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises about 1.0 to about 15% (w/w) micronized levodopa, about 0.1 to about 2.0% (w/w) micronized carbidopa, about 1.0 to about 5.0% (w/w) micronized entacapone, and about 1.0 to about 7.5% (w/w) sodium carboxymethyl cellulose.

9. The pharmaceutical composition of claim 5 , wherein the pH of the pharmaceutical composition is greater than about 5.0, and the viscosity of the aqueous carrier after 12 days at 25° C. is at least about 300 mPas at a moderate shear rate.

10. The pharmaceutical composition of claim 1 , wherein the weight ratio of carbidopa to levodopa is about 1:10 to about 1:2, or about 1:5 to about 1:3.

11. The pharmaceutical composition of claim 1 , wherein the weight ratio of entacapone to levodopa is about 10:1 to about 2:1, or 5:1 to 3:1.

12. A pharmaceutical composition for intra-intestinal administration, comprising about 20 mg/ml of levodopa, about 5 mg/ml of carbidopa, and about 20 mg/ml of entacapone.

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition has a pH of about 4.5 to about 5.5.

14. The pharmaceutical composition of claim 12 , wherein the levodopa, the carbidopa, and the entacapone are in the form of particles, wherein the particles are suspended in an aqueous carrier, and have a particle size no greater than 80 μm; and the aqueous carrier has a viscosity of at least 300 mPas at a moderate shear rate.

15. The pharmaceutical composition of claim 14 , wherein the aqueous carrier comprises a polysaccharide selected from the group consisting of cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, salts thereof, and combinations thereof.

16. The pharmaceutical composition of claim 15 , wherein the aqueous carrier comprises sodium carboxymethyl cellulose.

17. The pharmaceutical composition of claim 12 , wherein the pH of the pharmaceutical composition is greater than about 5.0, and the viscosity of the aqueous carrier after 12 days at 25° C. is at least about 300 mPas at a moderate shear rate.

18. A method of treating a neurodegenerative disease comprising administering intra-intestinally a pharmaceutical composition of claim 1 to a subject in need thereof.

19. A method of treating Parkinson's Disease, Alzheimer's Disease, or Huntington's Disease comprising administering intra-intestinally a pharmaceutical composition of claim 1 to a subject in need thereof.

20. The pharmaceutical composition according to claim 1 wherein the composition is in the form of a gel suspension.

21. A method of treating a neurodegenerative disease comprising administering intra-intestinally a pharmaceutical composition of claim 16 to a subject in need thereof.

22. A method of treating Parkinson's Disease, Alzheimer's Disease, or Huntington's Disease comprising administering intra-intestinally a pharmaceutical composition of claim 16 to a subject in need thereof.

23. The pharmaceutical composition according to claim 16 wherein the composition is in the form of a gel suspension.