Claims for Patent: 10,292,935

Summary for Patent: 10,292,935

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):	Hsu Ann, Dong Liang C., Ding Amy, Gupta Suneel
Assignee:	Impax Laboratories, Inc.
Application Number:	US15092086
Patent Claims:	1. A multiparticulate controlled release oral solid formulation comprising:(a) a plurality of controlled release particles comprising: i) a core comprising levodopa, optionally carbidopa, and at least one pharmaceutically acceptable excipient, ii) a layer or coating applied to the core comprising a muco-adhesive polymer; iii) and an enteric coating surrounding the core and the muco-adhesive layer or coating;(b) an immediate release component comprising levodopa, optionally carbidopa; andwherein the controlled release particles pass through a 12 mesh screen and are retained on a 25 mesh screen and comprise a controlled release material and the controlled release material is: A) mixed with the levodopa and at least one pharmaceutically acceptable excipient to form a controlled release matrix core; B) applied as a coating or layer onto the core comprising the levodopa and at least one pharmaceutically acceptable excipient; C) incorporated into the muco-adhesive coating or layer; or D) a combination of (A), (B) and/or (C); andwherein the solid oral formulation does not comprise an organic acid in the core other than levodopa and carbidopa and the solid oral dosage formulation releases at least 90% of the levodopa in approximately 5 to 7 hours when tested in a United States Pharmacopeia (USP) Type I dissolution apparatus at 37° C. with a rotational speed of 75 rpms and 900 mL of simulated gastric fluid with a pH of 1.0 for 2 hours followed by simulated intestinal fluid with a pH of 7.0.2. The multiparticulate formulation of wherein the controlled release material undercoats the muco-adhesive coating or layer and is a rate-controlling polymer.3. The multiparticulate formulation of claim 1 , wherein the controlled release particles are a mini-tablet claim 1 , bead claim 1 , pellet claim 1 , or granule.4. The multiparticulate formulation of claim 1 , wherein the immediate release component is a powder claim 1 , mini-tablet claim 1 , bead claim 1 , pellet claim 1 , granule claim 1 , a coating applied to the controlled release particles claim 1 , or a combination thereof.5. The multiparticulate formulation of wherein the carbidopa in the immediate release component is not optional.6. The multiparticulate formulation of claim 1 , wherein the controlled release particles and immediate release component are in a capsule.7. The multiparticulate formulation of claim 1 , wherein the muco-adhesive polymer is selected from the group consisting of amino methacrylate copolymer claim 1 , polycarbophil claim 1 , carbomer claim 1 , cellulosics claim 1 , chitosan claim 1 , diethylaminodextran claim 1 , diethylaminoethyldextran claim 1 , polygalactosamine claim 1 , polylysine claim 1 , polyomithine claim 1 , prolamine claim 1 , polyimine claim 1 , hyaluronic acid claim 1 , sodium alginate claim 1 , sodium carboxymethylcellulose (sodium CMC) and alginate or a combination thereof.8. The multiparticulate formulation of claim 7 , wherein the muco-adhesive polymer is an amino methacrylate copolymer.9. The multiparticulate formulation of claim 8 , wherein the amino methacrylate copolymer is a dimethylaminoethyl methacrylate copolymer.10. The multiparticulate formulation of claim 1 , wherein the enteric coating comprises a methacrylic acid copolymer.11. The multiparticulate formulation of claim 2 , wherein the rate-controlling polymer comprises cellulose acetate or ethylcellulose.12. The multiparticulate formulation of having an in vivo levodopa plasma profile following administration of an oral dosage form of the 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 5.0 hours.13. The multiparticulate formulation of claim 12 , wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 5.5 hours.14. The multiparticulate formulation of claim 12 , wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 6.0 hours.15. The multiparticulate formulation of claim 12 , wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 6.5 hours.16. The multiparticulate formulation of claim 12 , wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 7.0 hours.17. The multiparticulate formulation of claim 12 , wherein the in vivo plasma level of levodopa is maintained at 50% Cmax or above for at least 5.0 hours under fed conditions.18. A method of treating Parkinson's disease or primary parkinsonism comprising claim 1 , administering to the subject an effective amount of the multiparticulate formulation of .19. The multiparticulate formulation of wherein the controlled release particles have a size that passes through a 14 mesh screen but are retained on a 24 mesh screen.20. The multiparticulate formulation of wherein the carbidopa of the controlled release particles is not optional.