Claims for Patent: 12,178,918

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Summary for Patent: 12,178,918

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 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:	US18/755,045
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,178,918
Patent Claims:	1. A multiparticulate controlled release levodopa solid oral dosage form comprising: (i) one or more immediate release levodopa granules; and (ii) one or more controlled release levodopa particles comprising: (a) a spheronized core comprising levodopa and at least one pharmaceutically acceptable excipient selected from the group consisting of a binder, a filler, a wetting agent, and mixtures thereof; (b) a rate controlling coating surrounding the spheronized core wherein the rate controlling coating comprises a rate controlling material; (c) a muco-adhesive coating surrounding the rate controlling coating wherein the muco-adhesive coating comprises a muco-adhesive material capable of forming a positive ionic charge at pHs present in a human gastro-intestinal tract; and (d) an enteric coating surrounding the muco-adhesive coating wherein the enteric coating comprises an enteric material. 2. The dosage form of claim 1, wherein the rate controlling material comprises a rate controlling polymer selected from the group consisting of cellulose acetate, ethyl cellulose, and a mixture thereof. 3. The dosage form of claim 1, wherein the muco-adhesive material comprises a cationic muco-adhesive polymer. 4. The dosage form of claim 3, wherein the cationic muco-adhesive polymer is an amino methacrylate copolymer. 5. The dosage form of claim 4, wherein the amino methacrylate copolymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate). 6. The dosage form of claim 1, wherein the spheronized core is a spheronized bead. 7. The dosage form of claim 6, wherein the spheronized bead has a size of between 0.8 to 1.2 mm. 8. The dosage form of claim 7, wherein the spheronized bead coated with the rate controlling coating, the muco-adhesive coating, and the enteric coating passes through a mesh screen size of 16 or less and is retained on a mesh screen size of at least 18. 9. The dosage form of claim 1, wherein the controlled release levodopa particles do not include carbidopa. 10. The dosage form of claim 1, wherein the immediate release levodopa granules comprise levodopa and carbidopa. 11. A multiparticulate controlled release levodopa solid oral dosage form comprising: one or more controlled release levodopa particles comprising: (a) a core comprising levodopa and at least one pharmaceutically acceptable excipient selected from the group consisting of a binder, a filler, a wetting agent, and mixtures thereof; (b) a rate controlling coating surrounding the core wherein the rate controlling coating comprises a rate controlling material; (c) a muco-adhesive coating surrounding the rate controlling coating wherein the muco-adhesive coating comprises a muco-adhesive material capable of forming a positive ionic charge at pHs present in a human gastro-intestinal tract; and (d) an enteric coating surrounding the muco-adhesive coating wherein the enteric coating comprises an enteric material. 12. The dosage form of claim 11, wherein the rate controlling material is a rate controlling polymer selected from the group consisting of cellulose acetate, ethyl cellulose, and a mixture thereof. 13. The dosage form of claim 11, wherein the muco-adhesive material comprises a cationic muco-adhesive polymer. 14. The dosage form of claim 13, wherein the cationic muco-adhesive polymer is an amino methacrylate copolymer. 15. The dosage form of claim 14, wherein the amino methacrylate copolymer is poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate). 16. The dosage form of claim 11, wherein the core is a bead. 17. The dosage form of claim 16, wherein the bead has a size of between 0.8 to 1.2 mm. 18. The dosage form of claim 17, wherein the bead coated with the rate controlling coating, the muco-adhesive coating and the enteric coating passes through a mesh screen size of 16 or less and is retained on a mesh screen size of at least 18. 19. The dosage form of claim 11 further comprising an immediate release component comprising levodopa and carbidopa and the controlled release levodopa particles do not include carbidopa. 20. A multiparticulate controlled release levodopa solid oral dosage form comprising: (i) an immediate release component comprising one or more immediate release levodopa granules; and (ii) a controlled release component comprising one or more controlled release levodopa particles comprising: (a) a spheronized core comprising levodopa and (b) a muco-adhesive coating surrounding the spheronized core wherein the muco-adhesive coating comprises a muco-adhesive material capable of forming a positive ionic charge at pHs present in a human gastro-intestinal tract, and wherein ratio of levodopa in the controlled release component:levodopa in the immediate release component is about 3:1. 21. The dosage form of claim 20, wherein the dosage form provides an in vivo levodopa plasma profile following oral administration of the multiparticulate formulation to a human subject under fasting conditions comprising: (a) a levodopa plasma concentration corresponding to a maximum levodopa plasma concentration (Cmax) occurring within 6 hours after administration of the multiparticulate formulation; (b) a time to reach 50% Cmax of less than one hour after administration of the multiparticulate formulation; and (c) wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 5.0 hours after administration of the multiparticulate formulation.