Claims for Patent: 11,622,941

Summary for Patent: 11,622,941

Title:	Muco-adhesive, controlled release formulations 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 layer of a muco-adhesive polymer and externally coated with a layer of an enteric polymer; and (b) an immediate release component comprising carbidopa and levodopa.
Inventor(s):	Ann Hsu, Liang Dong, Amy Ding, Suneel Gupta
Assignee:	Impax Laboratories LLC
Application Number:	US17/372,434
Patent Claims:	1. A multiparticulate controlled release formulation comprising: (a) a controlled release component comprising a plurality of controlled release particles comprising a core comprising levodopa or levodopa equivalence, a mucoadhesive layer or coat surrounding the core; and an enteric coat or layer surrounding the mucoadhesive layer or coat, wherein mucoadhesive layer or coat comprises a cationic mucoadhesive polymer; and (b) an immediate release component comprising levodopa and carbidopa. 2. The multiparticulate controlled release formulation of claim 1, wherein the core of the controlled release component is a spheronized core. 3. The multiparticulate controlled release formulation of claim 2, wherein the spheronized core is a spheronized bead. 4. The multiparticulate controlled release formulation of claim 1, wherein the core of the controlled release component is an extruded and spheronized core. 5. The multiparticulate controlled release formulation of claim 1, wherein the cationic mucoadhesive polymer is an aminoalkyl methacrylate copolymer. 6. The multiparticulate controlled release formulation of claim 1, wherein the cationic mucoadhesive copolymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) (1:2:1). 7. The multiparticulate controlled release formulation of claim 1, wherein the controlled release component passes through a mesh screen size of 16 or less and is retained on a mesh screen size of at least 18. 8. The multiparticulate formulation of claim 1, wherein the controlled release component passes through a mesh screen size of 16 or less and is retained on a mesh screen size of 24. 9. The multiparticulate formulation of claim 1, wherein the controlled release component passes through a mesh screen size of 12 and is retained on a mesh screen size of 24. 10. The multiparticulate controlled release formulation of claim 1, wherein the controlled release component releases less than 20% of the levodopa within two hours, measured using a United States Pharmacopeia (USP) Type I apparatus at 75 rpm, in about 900 ml of a dissolution medium at pH of about 1. 11. The multiparticulate formulation of claim 1, wherein the formulation releases from about 75% to about 100% of the carbidopa in 30 minutes or less, measured using United States Pharmacopeia (USP) Type I or Type II apparatus, in about 500-900 mL of an aqueous medium with a pH from about 1 to about 7.5. 12. The multiparticulate controlled release formulation of claim 1, wherein the formulation releases from about 85% to about 100% of the carbidopa in 30 minutes or less, measured using USP Type I or Type II apparatus, in about 500-900 mL of an aqueous medium with a pH from about 1 to about 7.5. 13. The multiparticulate controlled release formulation of claim 1, further comprising a rate-controlling coat or layer which undercoats the mucoadhesive layer or coat within the controlled release particles. 14. The multiparticulate controlled release formulation of claim 13, wherein the rate-controlling coat or layer comprises ethylcellulose or cellulose acetate. 15. The multiparticulate controlled release formulation of claim 1, wherein the immediate release component (b) is formulated as a granule. 16. The multiparticulate controlled release formulation of claim 1, wherein the formulation is encapsulated in a capsule. 17. The multiparticulate controlled release formulation of claim 1, wherein the enteric coat or layer comprises one or more methacrylic acid copolymers. 18. A multiparticulate controlled release formulation comprising a plurality of controlled release particles comprising a spheronized core comprising levodopa or levodopa equivalence; a mucoadhesive layer or coat surrounding the core; and an enteric coat or surrounding the mucoadhesive layer or coat. 19. The multiparticulate controlled release formulation of claim 18, wherein the spheronized core is a spheronized bead. 20. The multiparticulate controlled release formulation of claim 19, wherein the spheronized bead passes through a mesh screen size of 12 and is retained on a mesh screen size of 24. 21. The multiparticulate controlled release formulation of claim 18, wherein the mucoadhesive layer or coat comprises a cationic mucoadhesive polymer. 22. The multiparticulate controlled release formulation of claim 21, wherein the cationic mucoadhesive polymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) (1:2:1). 23. The multiparticulate controlled release formulation of claim 18, further comprising a rate-controlling coat or layer which undercoats the mucoadhesive layer or coat within the controlled release particles. 24. The multiparticulate controlled release formulation of claim 23, wherein the rate-controlling coat or layer comprises ethylcellulose or cellulose acetate. 25. The multiparticulate controlled release formulation of claim 18, wherein the formulation further comprises a plurality of immediate release particles comprising levodopa or levodopa equivalence. 26. The multiparticulate controlled release formulation of claim 25, wherein the immediate release particles further comprise carbidopa or carbidopa equivalence. 27. The multiparticulate controlled release formulation of claim 25, wherein the immediate release particles are immediate release granules. 28. A multiparticulate controlled release formulation comprising a plurality of controlled release particles comprising a core comprising levodopa or levodopa equivalence; a mucoadhesive layer or coat surrounding the core; and an enteric coat or surrounding the mucoadhesive layer or coat, wherein the formulation comprises from 90 mg to 500 mg of levodopa or levodopa equivalence. 29. The multiparticulate controlled release formulation of claim 28, wherein the formulation further comprises a plurality of immediate release particles.