Claims for Patent: 12,403,099

Summary for Patent: 12,403,099

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, esters or salts thereof and wherein the one or more controlled release components; and (b) one or more immediate release components comprising levodopa, esters or salts thereof. The oral solid formulation also contains a decarboxylase inhibitor and about 80% to 100% of the decarboxylase inhibitor present in the oral solid formulation is present in the one or more immediate release components.
Inventor(s):	Ann Hsu, Liang Dong, Amy Ding, Suneel Gupta
Assignee:	Impax Laboratories LLC
Application Number:	US19/004,850
Patent Claims:	1. A capsule comprising 95 mg to 390 mg±10% of levodopa wherein the capsule contains: (i) one or more immediate release components comprising levodopa and carbidopa, and (ii) a plurality of controlled release components comprising: (a) a core comprising levodopa, at least one filler, at least one binder and at least one surfactant; (b) a controlled release coating comprising a controlled release polymer surrounding the core; (c) a muco-adhesive coating comprising a poly (butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methylmethacrylate) surrounding the controlled release coating; and (d) an enteric coating comprising an enteric polymer that dissolves at a pH greater than 5.5 surrounding the mucoadhesive coating; and (iii) optionally additional glidant or lubricant, wherein the plurality of controlled release components are free of carbidopa and pass through a 12 mesh screen and retained on a 25 mesh screen; wherein the filler comprises about 1 wt % to about 50 wt % of the total weight of the controlled release components, the binder comprises about 0.1 wt % to about 15 wt % of the total weight of the controlled release components and the surfactant comprises about 0.1 wt % to about 15 wt % of the total weight of the controlled release components; and wherein the ratio of levodopa in the plurality of controlled release components to levodopa in the one or more immediate release components is about 2:1 to about 3:1. 2. The capsule of claim 1 wherein the ratio of levodopa in the plurality of controlled release components to levodopa in the one or more immediate release components is about 3:1. 3. The capsule of claim 2 wherein: the plurality of controlled release components are beads; the filler in the core of the controlled release beads comprises mannitol, microcrystalline cellulose or a combination thereof; the binder in the core of the controlled release beads is povidone; and the surfactant in the core of the controlled release beads is sodium lauryl sulfate. 4. The capsule of claim 3 wherein the controlled release polymer comprises cellulose acetate or ethylcellulose. 5. The capsule of claim 3 wherein the enteric polymer is a methacrylic acid copolymer. 6. The capsule of claim 3 wherein the filler in the core of the controlled release beads comprises about 5 wt % to about 40 wt % of the total weight of the controlled release beads and is combination of mannitol and microcrystalline cellulose. 7. The capsule of claim 3 wherein the surfactant in the core of the controlled release beads comprises about 0.2 wt % to about 10 wt % of the total weight of the controlled release beads. 8. The capsule of claim 3 wherein the controlled release polymer is cellulose acetate. 9. The capsule of claim 3 wherein the immediate release components are a plurality of beads or granules comprising carbidopa, levodopa, at least one disintegrant, at least one binder and at least one lubricant. 10. The capsule of claim 9 wherein the at least one disintegrant in the immediate release beads or granules is croscarmellose sodium. 11. The capsule of claim 9 wherein the at least one binder in the immediate release beads or granules is povidone. 12. The capsule composition of claim 9 wherein the at least one lubricant in the immediate release beads or granules is magnesium stearate. 13. The capsule of claim 9 wherein: the one or more immediate release components are beads or granules comprising levodopa, carbidopa, croscarmellose sodium, povidone and magnesium stearate; the plurality of controlled release components are beads comprising: (a) an extruded and spheronized core comprising levodopa, mannitol, microcrystalline cellulose, povidone, and sodium lauryl sulfate; (b) the controlled release coating comprises cellulose acetate and copovidone; (c) the muco-adhesive coating comprising a poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methylmethacrylate) and talc; and (d) the enteric coating comprises a poly(methacrylic acid-co-ethyl methacrylate) copolymer, or a poly(methacrylic acid-co-methyl acrylate) copolymer, talc and triethyl citrate; and wherein the capsule content is free of any pH adjusting acid and the capsule releases at least 90% of the levodopa in approximately 5 to 7 hours when tested in a United States Pharmacopeia Type I dissolution apparatus at 37° C., with a rotational speed of 75 rpms and 900 mL of simulated gastric fluid with a pH o 1.0 for 2 hours followed by simulated intestinal fluid with a pH of 7.0. 14. The capsule of claim 13 comprising about 140 mg of levodopa and about 35 mg of carbidopa, based on the anhydrous weight of carbidopa. 15. The capsule of claim 13 comprising about 210 mg of levodopa and about 52.5 mg of carbidopa, based on the anhydrous weight of carbidopa. 16. The capsule of claim 13 comprising about 280 mg of levodopa and about 70 mg of carbidopa, based on the anhydrous weight of carbidopa. 17. The capsule of claim 13 comprising about 350 mg of levodopa and about 87.5 mg of carbidopa, based on the anhydrous weight of carbidopa. 18. A capsule comprising about 140 mg to about 350 mg levodopa wherein the capsule consists of: (i) one or more immediate release beads or granules comprising levodopa, carbidopa, croscarmellose sodium, povidone and magnesium stearate, and (ii) a plurality of controlled release beads comprising: (a) an extruded and spheronized core comprising levodopa, mannitol, microcrystalline cellulose, povidone, and sodium lauryl sulfate; (b) a controlled release coating comprising cellulose acetate and copovidone surrounding the core; (c) a muco-adhesive coating comprising a poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methylmethacrylate) and talc surrounding the controlled release coating; and (d) an enteric coating comprising a poly(methacrylic acid-co-methyl methacrylate) copolymer, talc and triethyl citrate surrounding the mucoadhesive coating; and (iii) optionally additional glidant or lubricant, wherein the plurality of controlled release beads are free of carbidopa and pass through a 12 mesh screen and retained on a 25 mesh screen; wherein the ratio of levodopa in the plurality of controlled release components to levodopa in the one or more immediate release components is about 3:1; wherein the capsule content is free of any pH adjusting acid. 19. The capsule of claim 18 wherein the capsule releases at least 90% of the levodopa in approximately 5 to 7 hours when tested in a United States Pharmacopeia Type I dissolution apparatus at 37° C., with a rotational speed of 75 rpms and 900 mL of simulated gastric fluid with a pH o 1.0 for 2 hours followed by simulated intestinal fluid with a pH of 7.0.