Muco-adhesive, controlled release formulation of levodopa and/or esters of levodopa and uses thereof
The invention provides an oral solid formulation comprising (a) a controlled release component comprising a core comprising levodopa, wherein the core is coated with a muco-adhesive coating and the muco-adhesive coating is externally coated with an enteric coating; and (b) an immediate release component comprising levodopa. The invention further provides a method for making and using the oral solid formulation.
1. A multiparticulate controlled release formulation comprising:
i) an immediate release component comprising levodopa, esters or salts thereof and a decarboxylase inhibitor, and
ii) a controlled release component comprising a core comprising levodopa, esters or salts thereof,
wherein the formulation is free of a pH adjusting carboxylic acid.
2. The multiparticulate controlled release formulation of claim 1 , wherein the controlled release component is free of the decarboxylase inhibitor.
3. The multiparticulate controlled release formulation of claim 1 , wherein the immediate release component comprises from about 80% to about 100% of the total amount of decarboxylase inhibitor in the multiparticulate controlled release formulation.
4. The multiparticulate controlled release formulation of claim 1 , wherein the controlled release component further comprises a mucoadhesive coating over the core.
5. The multiparticulate controlled release formulation of claim 4 , wherein the controlled release component further comprises a controlled release coating which undercoats the mucoadhesive coating.
6. The multiparticulate controlled release formulation of claim 5 , wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof.
7. The multiparticulate controlled release formulation of claim 4 , wherein the mucoadhesive coating comprises a mucoadhesive polymer that is capable of forming a positive ionic charge at a pH of a human gastrointestinal tract.
8. The multiparticulate controlled release formulation of claim 7 , wherein the mucoadhesive polymer is amino methacrylate copolymer.
9. The controlled release formulation of claim 8 , wherein the amino methacrylate copolymer is a poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate).
10. The multiparticulate controlled release formulation of claim 4 , wherein the formulation further comprises a coating comprising an enteric material surrounding the mucoadhesive coating.
11. The multiparticulate controlled release formulation of claim 1 , wherein the controlled release component passes through a number 12, 14, and/or 16 mesh screen.
12. The multiparticulate controlled release formulation of claim 1 , wherein the controlled release component is retained on a number 18, 24, and/or 25 mesh screen.
13. A multiparticulate controlled release formulation comprising:
i) an immediate release component comprising levodopa, esters or salts thereof and a decarboxylase inhibitor, and
ii) a controlled release component comprising a core comprising levodopa, esters or salts thereof,
wherein the formulation is free of a pH adjusting carboxylic acid, and
wherein the formulation on oral administration to a human subject under fasting conditions provides 50% of a maximum levodopa plasma concentration (50% C max ) within one hour of the administration of the formulation and the 50% C max plasma concentration of levodopa is maintained for at least about 3 hours.
14. The multiparticulate controlled release formulation of claim 13 , wherein the 50% C max plasma concentration of levodopa is maintained for at least about 5 hours.
15. The multiparticulate controlled release formulation of claim 13 , wherein the controlled release component is free of the decarboxylase inhibitor.
16. A multiparticulate controlled release formulation comprising:
i) an immediate release component comprising granules comprising levodopa, esters or salts thereof and a decarboxylase inhibitor, and
ii) a controlled release component comprising spheronized bead cores comprising levodopa, esters or salts thereof,
wherein the formulation is free of a pH adjusting carboxylic acid.
17. The multiparticulate controlled release formulation of claim 16 , wherein the controlled release component further comprises a mucoadhesive coating over the spheronized bead core.
18. The multiparticulate controlled release formulation of claim 17 , wherein the controlled release component further comprises a controlled release coating which undercoats the mucoadhesive coating.
19. The multiparticulate controlled release formulation of claim 18 , wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof.
20. The multiparticulate controlled release formulation of claim 17 , wherein the mucoadhesive coating comprises a mucoadhesive polymer that is capable of forming a positive ionic charge at a pH present in a human gastrointestinal tract.
21. The multiparticulate controlled release formulation of claim 16 , wherein the controlled release component is free of the decarboxylase inhibitor.
22. A method for treating Parkinson's disease or Primary Parkinsonism in a subject in need of such treatment comprising oral administration of a multiparticulate controlled release formulation comprising:
i) an immediate release component comprising levodopa, esters or salts thereof and a decarboxylase inhibitor, and
ii) a controlled release component comprising a core comprising levodopa, esters or salts thereof, and
wherein the formulation is free of a pH adjusting carboxylic acid.
23. The method of claim 22 , wherein the controlled release component is free of the decarboxylase inhibitor.