# US 12,178,919 B2 · Muco-adhesive, controlled release formulation of levodopa and/or esters of levodopa and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,178,919 B2 - Document ID: US12178919B2 - Status: Granted - Kind: B2 - Application number: 18/791,632 - Filed: 2024-08-01 - Published: 2024-12-05 - Granted: 2024-12-31 - Earliest claimed: 2013-10-07 - Assignees: Impax Laboratories, LLC - Applicants: Impax Laboratories, LLC - Inventors: Ann Hsu; Liang Dong; Amy Ding; Suneel Gupta - Web page: https://patentgrep.com/patent/US12178919B2 ## CPC - A61K 9/4808: {characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release (capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084)} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)} - A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)} - A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/5042: {Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose} - A61K 9/5073: {having two or more different coatings optionally including drug-containing subcoatings} - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - A61K 31/216: of acids having aromatic rings, e.g. benactizyne, clofibrate - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE ## 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. ## Claims ### Claim 1 A multiparticulate controlled release formulation comprising: i) an immediate release component comprising levodopa, esters or salts thereof and a decarboxylase inhibitor, and ii) a controlled release component comprising a core comprising levodopa, esters or salts thereof, wherein the formulation is free of a pH adjusting carboxylic acid. ### Claim 2 (depends on 1) The multiparticulate controlled release formulation of claim 1, wherein the controlled release component is free of the decarboxylase inhibitor. ### Claim 3 (depends on 1) The multiparticulate controlled release formulation of claim 1, wherein the immediate release component comprises from about 80% to about 100% of the total amount of decarboxylase inhibitor in the multiparticulate controlled release formulation. ### Claim 4 (depends on 1) The multiparticulate controlled release formulation of claim 1, wherein the controlled release component further comprises a mucoadhesive coating over the core. ### Claim 5 (depends on 4) The multiparticulate controlled release formulation of claim 4, wherein the controlled release component further comprises a controlled release coating which undercoats the mucoadhesive coating. ### Claim 6 (depends on 5) The multiparticulate controlled release formulation of claim 5, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. ### Claim 7 (depends on 4) The multiparticulate controlled release formulation of claim 4, wherein the mucoadhesive coating comprises a mucoadhesive polymer that is capable of forming a positive ionic charge at a pH of a human gastrointestinal tract. ### Claim 8 (depends on 7) The multiparticulate controlled release formulation of claim 7, wherein the mucoadhesive polymer is amino methacrylate copolymer. ### Claim 9 (depends on 8) The controlled release formulation of claim 8, wherein the amino methacrylate copolymer is a poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate). ### Claim 10 (depends on 4) The multiparticulate controlled release formulation of claim 4, wherein the formulation further comprises a coating comprising an enteric material surrounding the mucoadhesive coating. ### Claim 11 (depends on 1) The multiparticulate controlled release formulation of claim 1, wherein the controlled release component passes through a number 12, 14, and/or 16 mesh screen. ### Claim 12 (depends on 1) The multiparticulate controlled release formulation of claim 1, wherein the controlled release component is retained on a number 18, 24, and/or 25 mesh screen. ### Claim 13 A multiparticulate controlled release formulation comprising: i) an immediate release component comprising levodopa, esters or salts thereof and a decarboxylase inhibitor, and ii) a controlled release component comprising a core comprising levodopa, esters or salts thereof, wherein the formulation is free of a pH adjusting carboxylic acid, and wherein the formulation on oral administration to a human subject under fasting conditions provides 50% of a maximum levodopa plasma concentration (50% Cmax) within one hour of the administration of the formulation and the 50% Cmax plasma concentration of levodopa is maintained for at least about 3 hours. ### Claim 14 (depends on 13) The multiparticulate controlled release formulation of claim 13, wherein the 50% Cmax plasma concentration of levodopa is maintained for at least about 5 hours. ### Claim 15 (depends on 13) The multiparticulate controlled release formulation of claim 13, wherein the controlled release component is free of the decarboxylase inhibitor. ### Claim 16 A multiparticulate controlled release formulation comprising: i) an immediate release component comprising granules comprising levodopa, esters or salts thereof and a decarboxylase inhibitor, and ii) a controlled release component comprising spheronized bead cores comprising levodopa, esters or salts thereof, wherein the formulation is free of a pH adjusting carboxylic acid. ### Claim 17 (depends on 16) The multiparticulate controlled release formulation of claim 16, wherein the controlled release component further comprises a mucoadhesive coating over the spheronized bead core. ### Claim 18 (depends on 17) The multiparticulate controlled release formulation of claim 17, wherein the controlled release component further comprises a controlled release coating which undercoats the mucoadhesive coating. ### Claim 19 (depends on 18) The multiparticulate controlled release formulation of claim 18, wherein the controlled release coating comprises a controlled release material selected from the group consisting of ethyl cellulose, cellulose acetate, and mixtures thereof. ### Claim 20 (depends on 17) The multiparticulate controlled release formulation of claim 17, wherein the mucoadhesive coating comprises a mucoadhesive polymer that is capable of forming a positive ionic charge at a pH present in a human gastrointestinal tract. ### Claim 21 (depends on 16) The multiparticulate controlled release formulation of claim 16, wherein the controlled release component is free of the decarboxylase inhibitor. ### Claim 22 A method for treating Parkinson's disease or Primary Parkinsonism in a subject in need of such treatment comprising oral administration of a multiparticulate controlled release formulation comprising: i) an immediate release component comprising levodopa, esters or salts thereof and a decarboxylase inhibitor, and ii) a controlled release component comprising a core comprising levodopa, esters or salts thereof, and wherein the formulation is free of a pH adjusting carboxylic acid. ### Claim 23 (depends on 22) The method of claim 22, wherein the controlled release component is free of the decarboxylase inhibitor.