Pharmaceutical formulation for intraduodenal administration comprising melevodopa and carbidopa

1. An aqueous pharmaceutical formulation for intraduodenal administration, comprising carbidopa and melevodopa as active ingredients in a ratio of 1:5 by weight, and one or more excipients, wherein said melevodopa is completely dissolved, and said carbidopa is present as nanoparticles having a volume diameter of 100 to 1000 nm.

2. The formulation according to claim 1 , wherein said nanoparticles have a volume diameter of 200 to 900 nm.

3. The formulation according to claim 1 , wherein said one or more excipients comprise a component selected from the group consisting of a stabilization agent, a wetting agent, and mixtures thereof.

4. The formulation according to claim 3 , wherein said stabilization agent is selected from the group consisting of hydroxypropyl methylcellulose, polyvinylpyrrolidone, a vinylpyrrolidone-vinyl acetate copolymer, a methacrylic copolymer, carboxymethylcellulose, a carbomer, a plant gum, and a plant colloid, and mixtures thereof.

5. The formulation according to claim 3 , wherein said wetting agent is selected from the group consisting of a pharmaceutically acceptable salt of a fatty acid, a poloxamer, a polysorbate, sorbitan monolaurate, and mixtures thereof.

6. The formulation according to claim 1 , which further comprises one or more additional excipients selected from the group consisting of an antioxidant, a preserving agent, a pH regulating agent, and mixtures thereof.

7. The formulation according to claim 1 , wherein said carbidopa nanoparticles are prepared by a process comprising:

i) suspending carbidopa in the presence of one or more excipients in an acidic aqueous solution;

ii) milling the obtained suspension; and

iii) removing the aqueous medium.

8. The formulation according to claim 1 , wherein said carbidopa nanoparticles are prepared by a process comprising:

i) dissolving carbidopa in the presence of one or more excipients in an acidic aqueous solution of HCl;

ii) generating the carbidopa nanoparticles by controlled precipitation against a basic aqueous solution as anti-solvent using micro jet reactor technology; and

iii) removing the aqueous medium.

9. The pharmaceutical formulation according to claim 8 , wherein at least one of said excipients is adsorbed on the surface of the carbidopa nanoparticles in such a way as that said carbidopa nanoparticles are coated by the excipient.

10. A pharmaceutical formulation according to claim 1 , which is in a form of a dried powder to be reconstituted in water before use.

11. A pharmaceutical formulation according to claim 1 , wherein, said melevodopa is present in a concentration of 50 to 150 mg/ml, expressed as levodopa, and said carbidopa is present in a concentration of 5 to 30 mg/ml, expressed as carbidopa anhydrous.

12. The pharmaceutical formulation according to claim 11 , wherein said melevodopa is present in a concentration of 100 to 125 mg/ml, and said carbidopa is present in a concentration of 15 to 20 mg/ml.

13. A method for the treatment of Parkinson's disease, comprising administering to a subject in need thereof an effective amount of a formulation according to claim 1 .

14. A kit, comprising: a) a pharmaceutical formulation according to claim 10 ; b) a pharmaceutically acceptable aqueous vehicle; c) container means for containing the pharmaceutical formulation, and the aqueous vehicle; and d) an infusion pump.

15. The formulation according to claim 3 , wherein said stabilization agent is selected from the group consisting of xantan gum, guar gum, pectin, agar, an alginate, dextran, and mixtures thereof.

16. The formulation according to claim 3 , wherein said wetting agent comprises sodium octanoate.