Claims for Patent: 12,178,919

Summary for Patent: 12,178,919

Title:	Muco-adhesive, controlled release formulation of levodopa and/or esters of levodopa and uses thereof
Abstract:	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.
Inventor(s):	Ann Hsu, Liang Dong, Amy Ding, Suneel Gupta
Assignee:	Impax Laboratories LLC
Application Number:	US18/791,632
Patent Claims:	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% Cmax) within one hour of the administration of the formulation and the 50% Cmax plasma concentration of levodopa is maintained for at least about 3 hours. 14. The multiparticulate controlled release formulation of claim 13, wherein the 50% Cmax 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.