Muco-adhesive, controlled release formulation of levodopa and/or esters of levodopa and uses thereof

1 . A capsule comprising:

(i) one or more immediate release components comprising levodopa and carbidopa; and

(ii) one or more controlled release components comprising:

(a) a core comprising levodopa;

(b) a rate-controlling polymer coating comprising cellulose acetate surrounding the core;

(c) a muco-adhesive polymer coating comprising poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate) 1:2:1 surrounding the rate-controlling polymer coating; and

(d) an enteric polymer coating comprising a poly(methacrylic acid-co-methyl methacrylate) 1:1 copolymer surrounding the muco-adhesive polymer coating; and

wherein the controlled release components are free of carbidopa.

2 . The capsule of claim 1 wherein the immediate release components further comprise croscarmellose sodium, povidone, and magnesium stearate.

3 . The capsule of claim 2 wherein the core of the controlled release components further comprises microcrystalline cellulose, mannitol, sodium lauryl sulfate, and povidone.

4 . The capsule of claim 3 wherein the rate-controlling polymer coating of the controlled release components further comprises copovidone.

5 . The capsule of claim 4 wherein the muco-adhesive polymer coating of the controlled release components further comprises talc.

6 . The capsule of claim 5 wherein the enteric polymer coating of the controlled release components further comprises triethyl citrate and talc.

7 . The capsule of claim 6 wherein the capsule content is free of a pH adjusting acid.

8 . The capsule of claim 7 comprising 140 mg of levodopa and 35 mg of carbidopa, based on the anhydrous weight of carbidopa.

9 . The capsule of claim 7 comprising 210 mg of levodopa and 52.5 mg of carbidopa, based on the anhydrous weight of carbidopa.

10 . The capsule of claim 7 comprising 280 mg of levodopa and 70 mg of carbidopa, based on the anhydrous weight of carbidopa.

11 . The capsule of claim 7 comprising 350 mg of levodopa and 87.5 mg of carbidopa, based on the anhydrous weight of carbidopa.

12 . The capsule of claim 1 wherein the capsule produces an in vivo levodopa plasma profile following oral administration of the capsule to a subject under fasting conditions comprising:

(A) a levodopa plasma concentration corresponding to a maximum levodopa plasma concentration (C max ) occurring within 6 hours after administration of the capsule;

(B) a time to reach 50% C max of less than one hour; and

(C) wherein the in vivo plasma level of levodopa is maintained at 50% C max or above for at least 5.0 hours.

13 . A capsule consisting essentially of:

(i) one or more immediate release components consisting essentially of levodopa, carbidopa, croscarmellose sodium, povidone, and magnesium stearate; and

(ii) one or more controlled release components consisting essentially of:

(a) a core consisting essentially of levodopa, mannitol, microcrystalline cellulose, sodium lauryl sulfate and povidone;

(b) a rate-controlling polymer coating consisting essentially of cellulose acetate and copovidone surrounding the core;

(c) a muco-adhesive polymer coating consisting essentially of poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methylmethacrylate) 1:2:1 and talc surrounding the rate-controlling polymer coating; and

(d) an enteric polymer coating consisting essentially of a poly(methacrylic acid-co-methyl methacrylate) 1:1 copolymer, talc and triethyl citrate surrounding the muco-adhesive polymer coating; and

wherein the controlled release components are free of carbidopa.

14 . The capsule of claim 13 comprising 140 mg of levodopa and 35 mg of carbidopa, based on the anhydrous weight of carbidopa.

15 . The capsule of claim 13 comprising 210 mg of levodopa and 52.5 mg of carbidopa, based on the anhydrous weight of carbidopa.

16 . The capsule of claim 13 comprising 280 mg of levodopa and 70 mg of carbidopa, based on the anhydrous weight of carbidopa.

17 . The capsule of claim 13 comprising 350 mg of levodopa and 87.5 mg of carbidopa, based on the anhydrous weight of carbidopa.

18 . The capsule of claim 13 wherein the capsule produces an in vivo levodopa plasma profile following oral administration of the capsule to a subject under fasting conditions comprising:

(A) a levodopa plasma concentration corresponding to a maximum levodopa plasma concentration (C max ) occurring within 6 hours after administration of the capsule;

(B) a time to reach 50% C max of less than one hour; and

(C) wherein the in vivo plasma level of levodopa is maintained at 50% C max or above for at least 5.0 hours.

19 . A capsule consisting of:

(i) one or more immediate release components consisting essentially of levodopa, carbidopa, croscarmellose sodium, povidone, and magnesium stearate; and

(ii) one or more controlled release components consisting of:

(a) a core consisting of levodopa, mannitol, microcrystalline cellulose, sodium lauryl sulfate and povidone;

(b) a rate-controlling polymer coating consisting of cellulose acetate and copovidone surrounding the core;

(c) a muco-adhesive polymer coating consisting of poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methylmethacrylate) 1:2:1 and talc surrounding the rate-controlling polymer coating; and

(d) an enteric polymer coating consisting of a poly(methacrylic acid-co-methyl methacrylate) 1:1 copolymer, talc and triethyl citrate surrounding the muco-adhesive polymer coating.

20 . The capsule of claim 19 wherein the capsule produces an in vivo levodopa plasma profile following oral administration of the capsule to a subject under fasting conditions comprising:

(A) a levodopa plasma concentration corresponding to a maximum levodopa plasma concentration (C max ) occurring within 6 hours after administration of the capsule;

(B) a time to reach 50% C max of less than one hour; and

(C) wherein the in vivo plasma level of levodopa is maintained at 50% C max or above for at least 5.0 hours.