Claims for Patent: 12,303,605

Summary for Patent: 12,303,605

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) one or more controlled release components comprising a core comprising levodopa; and (b) one or more immediate release components comprising levodopa. The oral solid formulation also contains a decarboxylase inhibitor wherein the one or more controlled release components are substantially free of the decarboxylase inhibitor.
Inventor(s):	Ann Hsu, Liang Dong, Amy Ding, Suneel Gupta
Assignee:	Impax Laboratories LLC
Application Number:	US18/975,144
Patent Claims:	1. A controlled release formulation comprising: i) one or more immediate release components comprising levodopa and a decarboxylase inhibitor, and ii) one or more controlled release components comprising levodopa wherein the one or more controlled release components are substantially free of a decarboxylase inhibitor, wherein when the controlled release formulation is orally administered to a healthy subject in a single-dose crossover study with an immediate release oral carbidopa-levodopa-entacapone dosage form wherein the ratio of carbidopa to levodopa to entacapone in the immediate release carbidopa-levodopa-entacapone dosage form is 1:4:8, and the amount of levodopa orally administered with the controlled release formulation is 3.6 times the amount of levodopa administered with the immediate release carbidopa-levodopa-entacapone dosage form, a dose normalized levodopa AUC0-∞ value of about 55% to about 77% for the controlled release formulation is obtained compared to a dose normalized levodopa AUC0-∞ value obtained from the oral administration of the immediate release oral carbidopa-levodopa-entacapone dosage form. 2. The controlled release formulation of claim 1, wherein the one or more controlled release components are free of the decarboxylase inhibitor. 3. The controlled release formulation of claim 1, wherein the one or more immediate release components comprise from about 80% to about 100% of the total amount of decarboxylase inhibitor in the controlled release formulation. 4. The controlled release formulation of claim 1, wherein the one or more controlled release components comprise a core comprising levodopa. 5. The controlled release formulation of claim 4, wherein the core is coated with a coating comprising a mucoadhesive material. 6. The controlled release formulation of claim 5, wherein the one or more controlled release components further comprises a controlled release coating which undercoats the coating comprising the mucoadhesive material. 7. The controlled release formulation of claim 6, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. 8. The controlled release formulation of claim 7, wherein the coating comprising the mucoadhesive material comprises a mucoadhesive polymer that is capable of forming a positive ionic charge at a pH of a human gastrointestinal tract. 9. The controlled release formulation of claim 8, wherein the mucoadhesive polymer is amino methacrylate copolymer. 10. The controlled release formulation of claim 9, wherein the amino methacrylate copolymer is a poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate). 11. The controlled release formulation of claim 6, wherein the one or more controlled release components further comprises a coating comprising an enteric material surrounding the coating comprising the mucoadhesive material. 12. The controlled release formulation of claim 11 wherein the one or more controlled release components comprise an extruded spheronized core. 13. The controlled release formulation of claim 12 wherein the spheronized cores coated with the controlled release coating, the coating comprising the mucoadhesive material and the coating comprising the enteric material pass through a mesh screen size of 16 or less and are retained on a mesh screen size of at least 18. 14. A controlled release formulation comprising: i) one or more immediate release components comprising levodopa and a decarboxylase inhibitor, and ii) one or more controlled release components comprising levodopa wherein the one or more controlled release components are substantially free of a decarboxylase inhibitor, wherein when the controlled release formulation is orally administered to a healthy subject in a single-dose crossover study with an immediate release oral carbidopa-levodopa-entacapone dosage form wherein the ratio of carbidopa to levodopa to entacapone in the immediate release carbidopa-levodopa-entacapone dosage form is 1:4:8, and the amount of levodopa orally administered with the controlled release formulation is 3.6 times the amount of levodopa administered with the immediate release carbidopa-levodopa-entacapone dosage form, a dose normalized levodopa Cmax value of about 33% to about 50% for the controlled release formulation is obtained compared to a dose normalized levodopa Cmax value obtained from the oral administration of the immediate release oral carbidopa-levodopa-entacapone dosage form. 15. The controlled release formulation of claim 14, wherein the one or more controlled release components are free of the decarboxylase inhibitor. 16. The controlled release formulation of claim 14, wherein the one or more immediate release components comprise from about 80% to about 100% of the total amount of decarboxylase inhibitor in the controlled release formulation. 17. The controlled release formulation of claim 14, wherein the one or more controlled release components comprise a core comprising levodopa. 18. The controlled release formulation of claim 17, wherein the core is coated with a coating comprising a mucoadhesive material. 19. The controlled release formulation of claim 18, wherein the one or more controlled release components further comprises a controlled release coating which undercoats the coating comprising the mucoadhesive material. 20. The controlled release formulation of claim 19, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. 21. The controlled release formulation of claim 20, wherein the coating comprising a mucoadhesive material comprises a mucoadhesive polymer that is capable of forming a positive ionic charge at a pH of a human gastrointestinal tract. 22. The controlled release formulation of claim 21, wherein the mucoadhesive polymer is amino methacrylate copolymer. 23. The controlled release formulation of claim 22, wherein the amino methacrylate copolymer is a poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate). 24. The controlled release formulation of claim 19, wherein the one or more controlled release components further comprises a coating comprising an enteric material surrounding the coating comprising the mucoadhesive material. 25. The controlled release formulation of claim 24 wherein the one or more controlled release components comprise an extruded spheronized core. 26. The controlled release formulation of claim 25 wherein the spheronized cores coated with the controlled release coating, the coating comprising the mucoadhesive material and the coating comprising the enteric material pass through a mesh screen size of 16 or less and are retained on a mesh screen size of at least 18.