LEVODOPA DOSAGE FORM
The invention is a multiparticulate controlled release dosage form comprising 350 mg of levodopa for use in treating patients with Parkinson's disease, primary parkinsonism/idiopathic parkinsonism, post-encephalitic parkinsonism, parkinsonism that may follow carbon monoxide intoxication, or parkinsonism that may follow manganese intoxication and provides an improvement of a patient's total post-dose “On” time or “Good On” time compared to post-dose of treatment regimens with oral immediate release levodopa tablets.
1 . A multiparticulate controlled release dosage form comprising 350 mg of levodopa, wherein the dosage form on oral administration to a healthy human subject under fasted conditions, as a single 350 mg dose, provides a maximum levodopa plasma concentration (Cmax) of 1826.947±385.3425 (21.09%) ng/mL, wherein the plasma concentration is expressed as mean value±standard deviation (% variance).
2 . The dosage form of claim 1 comprising a plurality of controlled release components comprising a core comprising levodopa wherein the core is coated with a layer comprising a muco-adhesive polymer, and externally coated with a layer comprising an enteric polymer.
3 . The dosage form of claim 2 wherein the controlled release components further comprise a rate-controlling polymer layer which undercoats the layer of muco-adhesive polymer within the controlled release component.
4 . The dosage form of claim 2 , wherein the muco-adhesive polymer is selected from the group consisting of basic amino methacrylate copolymer, glyceride, steroidal detergent, polycarbophil, carbomer, cellulosics, chitosan, diethylaminodextran, diethylaminoethyldextran, polygalactosamine, polylysine, polyomithine, prolamine, polyimine, hyaluronic acid, sodiumalginate, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), sodium carboxymethylcellulose (sodium CMC), alginate, or combinations thereof.
5 . The dosage form of claim 4 , wherein the muco-adhesive polymer is basic amino methacrylate copolymer.
6 . The dosage form of claim 3 , wherein the rate controlling polymer is ethyl cellulose, cellulose acetate, or a mixture thereof.
7 . The dosage form of claim 2 , wherein the enteric polymer is selected from the group consisting of shellac (esters of aleurtic acid), zein, cellulose acetate phthalate (CAP), poly (methacrylic acid-co-methyl methacrylate), poly(methacrylic acid-co-ethyl acrylate), poly(vinyl acetate phthalate) (PVAP), hydroxypropyl methylcellulose phthalate (HPMCP) and hydroxypropyl methylcellulose acetate succinates, and mixtures thereof.
8 . The dosage form of claim 1 , wherein the dosage form is a capsule comprising multiparticulate controlled release components comprising levodopa.
9 . A multiparticulate controlled release dosage form comprising 350 mg of levodopa, wherein the dosage form on oral administration to a healthy human subject under fed conditions, as a single 350 mg dose, provides a maximum levodopa plasma concentration (Cmax) of 2185.564±472.7236 (21.63%) ng/mL, wherein the plasma concentration is mean concentration±standard deviation (% variance).
10 . The dosage form of claim 9 comprising a plurality of controlled release components comprising a core comprising levodopa wherein the core is coated with a layer comprising a muco-adhesive polymer, and externally coated with a layer comprising an enteric polymer.
11 . The dosage form of claim 9 wherein the controlled release components further comprise a rate-controlling polymer layer which undercoats the layer of muco-adhesive polymer within the controlled release component.
12 . The dosage form of claim 10 , wherein the muco-adhesive polymer is basic amino methacrylate copolymer.
13 . The dosage form of claim 11 , wherein the rate controlling polymer is ethyl cellulose, cellulose acetate, or a mixture thereof.
14 . The dosage form of claim 10 , wherein the enteric polymer is selected from the group consisting of shellac (esters of aleurtic acid), zein, cellulose acetate phthalate (CAP), poly (methacrylic acid-co-methyl methacrylate), poly(methacrylic acid-co-ethyl acrylate), poly(vinyl acetate phthalate) (PVAP), hydroxypropyl methylcellulose phthalate (HPMCP) and hydroxypropyl methylcellulose acetate succinates, and mixtures thereof.
15 . The dosage form of claim 9 , wherein the dosage form is a capsule comprising multiparticulate controlled release components comprising levodopa.
16 . A multiparticulate controlled release dosage form comprising 350 mg of levodopa, wherein the dosage form on oral administration to a healthy human subject, as a single 350 mg dose sprinkled on 1 tablespoon of apple sauce, provides a maximum levodopa plasma concentration of 1634.170±409.3129 (25.05%) ng/mL, wherein the plasma concentration is mean concentration±standard deviation (% variance).
17 . The dosage form of claim 16 comprising a plurality of controlled release components comprising a core comprising levodopa wherein the core is coated with a layer comprising a muco-adhesive polymer, and externally coated with a layer comprising an enteric polymer.
18 . The dosage form of claim 17 wherein the controlled release components further comprise a rate-controlling polymer layer which undercoats the layer of muco-adhesive polymer within the controlled release component.
19 . The dosage form of claim 17 , wherein the muco-adhesive polymer is basic amino methacrylate copolymer.
20 . The dosage form of claim 18 , wherein the rate controlling polymer is ethyl cellulose, cellulose acetate, or a mixture thereof.
21 . The dosage form of claim 17 , wherein the enteric polymer is selected from the group consisting of shellac (esters of aleurtic acid), zein, cellulose acetate phthalate (CAP), poly (methacrylic acid-co-methyl methacrylate), poly(methacrylic acid-co-ethyl acrylate), poly(vinyl acetate phthalate) (PVAP), hydroxypropyl methylcellulose phthalate (HPMCP) and hydroxypropyl methylcellulose acetate succinates, and mixtures thereof.