Claims for Patent: 10,987,313

Summary for Patent: 10,987,313

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:	US16/573,634
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 components wherein one or more of the controlled release levodopa components comprise one or more beads, pellets, tablets, minitablets, or granules comprising: (a) 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 and wherein the dosage form comprises 90 mg to 500 mg of levodopa. 2. The dosage form of claim 1 wherein the immediate release levodopa component comprises levodopa and is a powder, coating, tablet, mini-tablet, bead, pellet, granule or combination thereof. 3. The dosage form of claim 1 comprising 95 mg to 390 mg levodopa. 4. The dosage form of claim 1 comprising 145 mg; 195 mg, 200 mg, 245 mg, 255.6 mg, 360 mg or 390 mg of levodopa±10%. 5. The dosage form of claim 1 further comprising carbidopa. 6. The dosage form of claim 5 wherein the carbidopa is anhydrous. 7. The dosage form of claim 5 wherein the one or more controlled release levodopa components are substantially free of controlled release carbidopa. 8. The dosage form of claim 5 wherein the one or more controlled release levodopa components are free of controlled release carbidopa. 9. The dosage form of claim 5 wherein the dosage form is substantially free of controlled release carbidopa. 10. The dosage form of claim 5 wherein the dosage form is free of controlled release carbidopa. 11. The dosage form of claim 5 wherein the ratio of levodopa to carbidopa is about 4:1. 12. The dosage form of claim 1 wherein the dosage form is a capsule. 13. The dosage form of claim 5 comprising about 140 mg of levodopa and about 35 mg of carbidopa. 14. The dosage form of claim 5 comprising about 210 mg of levodopa and about 52.5 mg of carbidopa. 15. The dosage form of claim 5 comprising about 280 mg of levodopa and about 70 mg of carbidopa. 16. The dosage form of claim 5 comprising about 350 mg levodopa and 87.5 mg of carbidopa. 17. The dosage form of claim 5 wherein about 75% to 100% of the carbidopa is released within 30 minutes of in vitro testing using a USP type I or type II apparatus with 900 mL of an aqueous media with a pH of about 1 to about 7.5. 18. The dosage form of claim 1 wherein about 15% to 45% of the levodopa is released within 30 minutes of in vitro testing using a USP type I or type II apparatus with 900 mL of an aqueous media with a pH of about 1 to about 4.0. 19. The dosage form of claim 1 when tested using a USP Apparatus I at 75 rpms and 37°±0.5° C. with 500-900 ml of simulated gastric fluid for 2 hours and pH 6.8 phosphate buffer thereafter exhibits the following levodopa release profile: 20% to 60% of levodopa is released after 2 hours; 40% to 80% of levodopa is released after 3 hours; 60% to 100% of levodopa is release after 4 hours; and not less than 80% is released after 7 hours. 20. A method of treating Parkinson's disease comprising administering to a patient in need of such treatment, one or more capsules comprising: (i) one or more immediate release levodopa components; and (ii) one or more controlled release levodopa components wherein the one or more controlled release levodopa components comprise one or more beads, pellets, tablets, mini-tablet, or granules comprising: (a) 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 and wherein the capsules comprise 95 mg to 390 mg of levodopa. 21. The method of claim 20 wherein the immediate release levodopa component comprises levodopa and is a powder, coating, tablet, mini-tablet, bead, pellet, granule or combination thereof. 22. The method of claim 20 wherein the capsule comprises 145 mg; 195 mg, 200 mg, 245 mg, 255.6 mg, 360 mg or 390 mg of levodopa±10%. 23. The method of claim 20 wherein the capsule comprises carbidopa. 24. The method of claim 23 wherein the carbidopa is anhydrous. 25. The method of claim 23 wherein the controlled release levodopa components are substantially free of controlled release carbidopa. 26. The method of claim 23 wherein the controlled release levodopa components are free of controlled release carbidopa. 27. The method of claim 23 wherein the capsule is substantially free of controlled release carbidopa. 28. The method of claim 23 wherein the capsule is free of controlled release carbidopa. 29. The method of claim 23 wherein the ratio of levodopa to carbidopa is 4:1. 30. The method of claim 23 wherein the capsule comprises about 140 mg of levodopa and about 35 mg of carbidopa. 31. The method of claim 23 wherein the capsule comprises about 210 mg of levodopa and about 52.5 mg of carbidopa. 32. The method of claim 23 wherein the capsule comprises about 280 mg of levodopa and about 70 mg of carbidopa. 33. The method of claim 23 wherein the capsule comprises about 350 mg of levodopa and about 87.5 mg of carbidopa. 34. The method of claim 23 wherein the one or more capsules are administered by swallowing the capsules. 35. The method of claim 20 wherein the capsules are administered by opening the capsules and sprinkling the immediate release component and controlled release component onto food or liquid and swallowing the food or liquid with the immediate release component and controlled release component. 36. The method of claim 20 comprising administering the capsule every 7 to 8 hours. 37. The method of claim 20 wherein the administration produces a levodopa plasma level in the patient that is continuously above 50% of Cmax for 5.0 hours or longer. 38. The method of claim 20 wherein the administration produces a levodopa plasma level in the patient that is continuously above 50% of Cmax for 5.5 hours or longer. 39. The method of claim 20 wherein the administration produces a levodopa plasma level in the patient that is continuously above 50% of Cmax for 6.0 hours or greater. 40. The method of claim 37 wherein the levodopa plasma level is a mean levodopa plasma level. 41. The method of claim 37 wherein the levodopa plasma level is a mean levodopa plasma level after a single dose administration of the one or more capsules to the patient. 42. The method of claim 37 wherein the levodopa plasma level is a mean levodopa plasma level after multidose administration of the one or more capsules to the patient or at a steady state. 43. The method of claim 37 wherein the levodopa plasma level is a mean levodopa plasma level after administration of the one or more capsules to the patient in a fed state. 44. The method of claim 37 wherein the levodopa plasma level is a mean levodopa plasma level after administration of the one or more capsules to the patient in a fasting state.