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

1. A pharmaceutical gel composition for intra-intestinal administration, comprising a dopamine replacement agent, a dopamine decarboxylase inhibitor (DDI), and a catechol-O-methyltransferase (COMT) inhibitor.

2. The pharmaceutical gel composition of claim 1 , wherein the dopamine replacement agent is levodopa.

3. The pharmaceutical gel composition of claim 1 , wherein the dopamine decarboxylase inhibitor is selected from the group consisting of carbidopa, benserazide, and combinations thereof.

4. The pharmaceutical gel composition of claim 1 , wherein the COMT inhibitor is selected from the group consisting of entacapone, tolcapone, opicapone, and combinations thereof.

5. The pharmaceutical gel composition of claim 3 , wherein the gel composition further comprises a substance inhibiting degradation of carbidopa to hydrazine.

6. The pharmaceutical gel composition of claim 1 , wherein:

the gel composition has a pH value equal to or lower than about 5.7; or

the gel composition is deoxygenized; or

the gel composition further comprises an antioxidant; or

the gel composition is free from metal chelating agent; or

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

7. The pharmaceutical gel composition of claim 2 , wherein the levodopa, the DDI, and the COMT inhibitor are in the form of particles;

the particles are suspended in an aqueous carrier, and have the particle size no greater than 80 μm; and

the aqueous carrier has a viscosity of at least 300 mPas at a moderate shear rate.

8. The pharmaceutical gel composition of claim 7 , wherein the carrier is a polysaccharide selected from the group consisting of cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, salts thereof, and combinations thereof.

9. The pharmaceutical gel composition of claim 2 , wherein the gel 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.

10. The pharmaceutical gel composition of claim 9 , wherein the pH of the gel 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.

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

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

13. The pharmaceutical gel composition of claim 2 , wherein the composition comprises at least about 10 mg/ml of levodopa, at least about 2.5 mg/ml of a dopamine decarboxylase inhibitor, and at least about 10 mg/ml of a COMT inhibitor.

14. The composition of claim 2 , wherein the levodopa, the dopamine decarboxylase inhibitor and the COMT inhibitor are in the form of particles, wherein the particles are suspended in an aqueous carrier, and have a particle size of no greater than about 80 μm.

15. A method of preparing the pharmaceutical gel of claim 2 comprising: mixing levodopa, dopamine decarboxylase inhibitor and a COMT inhibitor with an aqueous carrier.

16. A method of treating a neurodegenerative disorder comprising intra-intestinal administration of the composition of claim 1 .

17. The method of claim 16 , wherein the neurodegenerative disorder is Parkinson's Disease, Alzheimer's Disease, or Huntington's Disease.