Claims for Patent: 11,666,538

Summary for Patent: 11,666,538

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:	US17/959,681
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,666,538
Patent Claims:	1. A controlled release oral solid formulation comprising (a) a controlled release component comprising a core comprising levodopa and/or an ester of levodopa or salts thereof, wherein the core is free of a decarboxylase inhibitor and is coated with a layer of a muco-adhesive polymer comprising an amino methacrylate copolymer, and externally coated with a layer of an enteric coating polymer; and (b) an immediate release component comprising levodopa and/or an ester of levodopa or salts thereof. 2. The controlled release oral solid formulation of claim 1 further comprising a rate-controlling polymer which undercoats the muco-adhesive polymer within the controlled release component. 3. The controlled release oral solid formulation of claim 1 wherein the controlled release component (a) is formulated as a bead. 4. The controlled release oral solid formulation of claim 3 wherein the muco-adhesive polymer constitutes 2% to 50% of the mass of the controlled release component and the controlled release bead size is between 0.8 to 1.2 mm. 5. The controlled release oral solid formulation of claim 3 wherein the controlled release bead is a size that passes through a 12 mesh screen but are retained on a 24 mesh screen. 6. The controlled release oral solid formulation of claim 3 wherein the controlled release bead is a size that passes through a 14 mesh but are retained on a 24 mesh screen. 7. The controlled release oral solid formulation of claim 3 wherein the controlled release bead is a size that passes through a 16 mesh but are retained on a 24 mesh screen. 8. The controlled release oral solid formulation of claim 1 wherein the immediate release component (b) further comprises carbidopa. 9. The controlled release oral solid formulation of claim 1, wherein the amino methacrylate copolymer comprises poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) 1:2:1. 10. The controlled release oral solid formulation of claim 1, wherein the muco-adhesive polymer layer also comprises an additional polymer selected from the group consisting of polycarbophil, carbomer, cellulosics, chitosan, diethylaminodextran, diethylaminoethyldextran, polygalactosamine, polylysine, polyomithine, prolamine, polyimine, hyaluronic acid, sodium alginate, sodium carboxymethylcellulose (sodium CMC), and alginate, or a combination thereof. 11. The controlled release oral solid formulation of claim 2, wherein the rate-controlling polymer comprises cellulose acetate or ethylcellulose. 12. The controlled release oral solid formulation of claim 2 wherein the core of the controlled release component (a) comprises levodopa and the immediate release component (b) comprises levodopa and carbidopa. 13. The controlled release oral solid formulation of claim 1, wherein the controlled release component (a) has an in vitro dissolution profile with less than 20% release of the levodopa and/or ester of levodopa or salts thereof at about pH 1.0 within two hours, measured using United States Pharmacopeia (USP) I dissolution method at 75 rpm. 14. The controlled release oral solid formulation of claim 1, wherein the controlled release component (a) has an in vitro dissolution profile with less than 10% release of the levodopa and/or ester of levodopa or salts thereof at about pH 1.0 within two hours, measured using United States Pharmacopeia (USP) I dissolution method at 75 rpm. 15. The controlled release oral solid formulation of claim 1, having an in vivo levodopa plasma profile following oral administration of the controlled release oral solid formulation to a subject under fasting conditions comprising (a) a time of administration; (b) a levodopa plasma concentration corresponding to maximum levodopa plasma concentration (Cmax) occurring within 6 hours after administration of the dosage form; (c) a time to reach 50% Cmax of less than one hour; and (d) wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 3 hours. 16. The controlled release formulation of claim 15, wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 4 hours. 17. The controlled release formulation of claim 15, wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 5.0 hours. 18. A method for treating Parkinson's disease or primary parkinsonism in a subject in need of such treatment comprising the oral administration of the controlled release oral solid formulation of claim 1. 19. The controlled release oral solid formulation of claim 1, wherein the levodopa, and/or ester of levodopa, and/or salts thereof are dispersed throughout the core or layered on a sugar sphere. 20. A controlled release oral solid formulation comprising (a) a plurality of controlled release beads comprising: (a) a spheronized core comprising levodopa wherein the core is free of a decarboxylase inhibitor; (b) a rate-controlling polymer layer; (c) a layer of a muco-adhesive polymer applied to the rate-controlling polymer layer wherein the layer of a muco-adhesive polymer comprises a cationic muco-adhesive polymer; and (d) an external layer of an enteric coating polymer; and (b) an immediate release component comprising levodopa and carbidopa; wherein the muco-adhesive polymer constitutes 2% to 50% of the mass of the controlled release bead and the controlled release bead size is between 0.8 mm to 1.2 mm. 21. The controlled release oral solid formulation of claim 20, wherein the cationic muco-adhesive polymer poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) 1:2:1.