Claims for Patent: 11,357,733

Summary for Patent: 11,357,733

Title:	Muco-adhesive, controlled release formulations of levodopa and/or esters of levodopa and uses thereof
Abstract:	The invention provides a controlled release oral solid formulation comprising (a) a controlled release component comprising core comprising levodopa and/or an ester of levodopa or salts thereof, wherein the core is coated with a layer of a muco-adhesive polymer and externally coated with a layer of an enteric coated polymer; and (b) a decarboxylase inhibitor component.
Inventor(s):	Ann Hsu, Liang Dong, Amy Ding, Suneel Gupta
Assignee:	Impax Laboratories LLC
Application Number:	US17/148,320
Patent Claims:	1. A multiparticulate controlled release levodopa solid oral dosage form comprising: (i) one or more immediate release levodopa components; and (ii) one or more controlled release levodopa particles wherein the one or more controlled release levodopa particles comprise: (a) a spheronized core comprising levodopa and at least one pharmaceutically acceptable excipient; (b) a coating surrounding the core comprising a muco-adhesive material; and (c) a coating comprising an enteric material surrounding the coating comprising the muco-adhesive material. 2. The dosage form of claim 1 wherein the one or more controlled release particles pass through a 12 mesh screen but are retained on a 25 mesh screen. 3. The dosage form of claim 1 wherein the one or more controlled release particles pass through a 14 mesh screen but are retained on a 24 mesh screen. 4. The dosage form of claim 1 wherein the one or more controlled release particles comprise an extruded and spheronized core. 5. The dosage form of claim 1 wherein the immediate release levodopa components comprise levodopa and is a powder, coating, mini-tablet, bead, pellet, granule or combination thereof. 6. The dosage form of claim 5 wherein the immediate release levodopa components comprise a powder or a granule. 7. The dosage form of claim 5 wherein the immediate release levodopa components comprise a coating applied to one or more of the controlled release levodopa particles. 8. The dosage form of claim 1, wherein the muco-adhesive material is selected from the group consisting of amino methacrylate copolymers, polycarbophil, carbomer, cellulosics, chitosan, diethylaminodextran, diethylaminoethyldextran, polygalactosamine, polylysine, polyomithine, prolamine, polyimine, hyaluronic acid, sodium alginate, sodium carboxymethylcellulose, alginate or a combination thereof. 9. The dosage form of claim 8, wherein the muco-adhesive material is an amino methacrylate copolymer. 10. The dosage form of claim 8, wherein the amino methacrylate copolymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate polymer. 11. The dosage form of claim 1, wherein the enteric material dissolves at a pH of greater than or equal to 5.5. 12. The dosage form of claim 11 wherein the enteric material comprises a methacrylic acid copolymer. 13. The dosage form of claim 1 wherein the core of the one or more controlled release particles comprises a mixture of levodopa and one or more pharmaceutically acceptable excipients selected from the group consisting of lubricants, fillers, binders, disintegrants, glidants, surfactants, pH adjusting agents, antioxidants or mixtures of the foregoing. 14. The dosage form of claim 1 wherein the core of the one or more controlled release particles comprises a mixture of levodopa, one or more fillers, one or more binders, and one or more surfactants. 15. The dosage form of claim 1 wherein dosage form releases at least 90% of the levodopa in approximately 5 to 7 hours when tested in a United States Pharmacopeia (USP) Type I dissolution apparatus at 37° C. with a rotational speed of 75 rpms and 900 mL of simulated gastric fluid with a pH of 1.0 for 2 hours followed by simulated intestinal fluid with a pH of 7.0. 16. The dosage form of claim 1 wherein the one or more controlled release particles further comprises a controlled release coating surrounding the core and wherein the controlled release coating is applied prior to the coating (b) comprising the muco-adhesive material. 17. The dosage form of claim 1 further comprising carbidopa. 18. The dosage form of claim 1 comprising about 95 mg to about 390 mg of levodopa. 19. The dosage form of claim 18 comprising about 140 mg of levodopa and about 35 mg of carbidopa. 20. The dosage form of claim 18 comprising about 210 mg of levodopa and about 52.5 mg of carbidopa. 21. The dosage form of claim 18 comprising about 280 mg of levodopa and about 70 mg of carbidopa. 22. The dosage form of claim 18 comprising about 350 mg levodopa and about 87.5 mg of carbidopa. 23. The dosage form of claim 1 wherein the one or more controlled release particles pass through a 12 mesh screen but are retained on a 25 mesh screen; the core of the one or more controlled release particles comprises an extruded and spheronized mixture of levodopa and one or more pharmaceutically acceptable excipients selected from the group consisting of lubricants, fillers, binders, disintegrants, glidants, surfactants, pH adjusting agents, antioxidants or mixtures of the foregoing and the dosage form comprises about 95 mg to about 390 mg of levodopa. 24. A capsule comprising: (i) one or more immediate release levodopa components; and (ii) a plurality of controlled release levodopa particles comprising: (a) a spheronized core comprising levodopa, one or more fillers and one or more binders; (b) a controlled release coating surrounding the spheronized core; (c) a muco-adhesive coating comprising a poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate polymer surrounding the controlled release coating; and (d) an enteric coating comprising a methacrylic acid copolymer that dissolves at a pH of 5.5 or greater surrounding the muco-adhesive coating. 25. The capsule of claim 24 wherein the one or more controlled release particles pass through a 12 mesh screen but are retained on a 25 mesh screen. 26. The capsule of claim 24 wherein the one or more controlled release particles pass through a 14 mesh screen but are retained on a 24 mesh screen. 27. The capsule of claim 24 wherein the one or more controlled release particles comprise an extruded and spheronized core comprising levodopa, one or more fillers, one or more binders, and one or more surfactants. 28. The capsule of claim 24 comprising about 95 mg to about 390 mg of levodopa. 29. The capsule of claim 24 wherein the immediate release levodopa components comprise levodopa and is a powder, coating, mini-tablet, bead, pellet, granule or combination thereof. 30. The capsule of claim 29 wherein the immediate release levodopa components comprises a powder or granule. 31. The capsule of claim 24 wherein the immediate release levodopa components comprise one or more granules comprising a mixture of levodopa, carbidopa and one or more pharmaceutically acceptable excipients selected from the group consisting of lubricants, fillers, binders, disintegrants, glidants, surfactants, pH adjusting agents, antioxidants or mixtures of the foregoing. 32. The capsule of claim 31 wherein the one or more immediate release granules comprise a mixture of levodopa, carbidopa, croscarmellose sodium, povidone and magnesium stearate. 33. The capsule of claim 29 wherein the immediate release levodopa components comprise a coating applied to one or more of the controlled release particles. 34. The capsule of claim 24 wherein the controlled release coating comprises ethylcellulose. 35. The capsule of claim 24 wherein the controlled release coating comprises cellulose acetate. 36. The capsule of claim 24 wherein the plurality of controlled release levodopa particles pass through a 14 mesh screen but are retained on a 24 mesh screen and comprise: (a) a spheronized core comprising levodopa, microcrystalline cellulose, mannitol, sodium lauryl sulfate and povidone; (b) a controlled release coating surrounding the spheronized core wherein the controlled release coating comprises cellulose acetate or ethylcellulose; (c) a muco-adhesive coating comprising a poly(butylmethacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate polymer surrounding the controlled release coating; and (d) an enteric coating comprising a methacrylic acid copolymer that dissolves at a pH of 5.5 or greater surrounding the muco-adhesive coating. 37. The capsule of claim 36 wherein the one or more immediate release levodopa components comprise one or more immediate release granules comprising a mixture of levodopa, carbidopa, one or more disintegrants and one or more binders. 38. The capsule of claim 37 wherein the one or more immediate release granules comprise a mixture of levodopa, carbidopa, croscarmellose sodium, povidone and magnesium stearate. 39. The capsule of claim 36 wherein the plurality of controlled release levodopa particles comprise an extruded and spheronized core comprising levodopa, microcrystalline cellulose, mannitol, sodium lauryl sulfate and povidone. 40. A capsule comprising: (i) one or more immediate release levodopa components; and (ii) a plurality of controlled release levodopa particles comprising: (a) an extruded spheronized core comprising levodopa, one or more fillers, and one or more binders; (b) a controlled release coating surrounding the spheronized core; (c) a muco-adhesive coating comprising a poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate polymer surrounding the controlled release coating; and (d) an enteric coating comprising a methacrylic acid copolymer that dissolves at a pH of 5.5 or greater surrounding the muco-adhesive coating; wherein the controlled release levodopa particles pass through a 12 mesh screen but are retained on a 25 mesh screen and the capsule contains about 95 mg to about 390 mg of levodopa.