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 a dopamine replacement agent selected from levodopa, melevodopa, etilevodopa and combinations thereof, a dopamine decarboxylase inhibitor (DDI) wherein the dopamine decarboxylase inhibitor is carbidopa, benzerazide or combination thereof, and a catechol-O-methyltransferase (COMT) inhibitor selected from entacapone, tolcapone, opicapone and combinations thereof; and

wherein the pharmaceutical composition comprises about 1.0 to about 15% (w/w) micronized dopamine replacement agent, about 0.1 to about 2.0% (w/w) micronized DDI, about 1.0 to about 5.0% (w/w) micronized COMT inhibitor, and about 1.0 to about 7.5% (w/w) sodium carboxymethyl cellulose.

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 dopamine replacement agent, the DDI, and the COMT inhibitor 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 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.

9. The pharmaceutical composition of claim 1 , wherein the weight ratio of DDI to COMT inhibitor is about 1:10 to about 1:2, or about 1:5 to about 1:3.

10. The pharmaceutical composition of claim 1 , wherein the weight ratio of COMT inhibitor to dopamine replacement agent is about 10:1 to about 2:1, or 5:1 to 3:1.

11. A pharmaceutical composition for intra-intestinal administration, comprising about 20 mg/ml of dopamine replacement agent, about 5 mg/ml of DDI, and about 20 mg/ml of COMT inhibitor.

12. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition has a pH of about 4.5 to about 5.5.

13. The pharmaceutical composition of claim 11 , wherein the dopamine replacement agent, the DDI, and the COMT inhibitor 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.

14. The pharmaceutical composition of claim 13 , 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.

15. The pharmaceutical composition of claim 14 , wherein the aqueous carrier comprises sodium carboxymethyl cellulose.

16. The pharmaceutical composition of claim 11 , 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.

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

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

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

20. A method of treating a neurodegenerative disease comprising administering intra-intestinally a pharmaceutical composition of claim 15 to a subject in need thereof.

21. A method of treating Parkinson's Disease, Alzheimer's Disease, or Huntington's Disease comprising administering intra-intestinally a pharmaceutical composition of claim 15 to a subject in need thereof.

22. The pharmaceutical composition according to claim 15 wherein the composition is in the form of a gel suspension.