Claims for Patent: 10,925,833

Summary for Patent: 10,925,833

Title:	Extended release compositions comprising pyridostigmine
Abstract:	Extended release pyridostigmine dosage forms, suitable for maintaining stable plasma concentrations with reduced or minimized initial burst release/dose dumping of pyridostigmine, are provided. The dosage forms include matrix tablets, gastroretentive tablets, and pellets, the latter being suitable for dosing in capsules, tablets, and sachets, as well as for sprinkling on foodstuffs. The disclosure also provides methods for improving patient compliance by administering once-a-day extended release pyridostigmine bromide dosage forms that provide a superior controlled drug release.
Inventor(s):	Namdev B. Shelke, Siva Ram Kiran Vaka, Dipen Desai, Wantanee Phuapradit, Navnit H. Shah
Assignee:	Amneal Complex Products Research LLC
Application Number:	US17/003,323
Patent Claims:	1. A gastroretentive dosage form comprising a core and a permeable elastic membrane containing at least one orifice and surrounding the core, wherein the core comprises from about 50 mg to about 400 mg of pyridostigmine or a pharmaceutically acceptable salt thereof, a swellable water-soluble hydrophilic polymer, an acid, and a gas-generating agent, wherein the permeable elastic membrane comprises a plasticizer, and a copolymer based on ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride (1:2:0.2), wherein the copolymer is present in an amount of from about 70 wt % to about 95 wt % of the membrane composition, wherein the plasticizer is present in an amount of from about 5 wt % to about 25 wt % of the membrane composition, and wherein the acid is selected from the group consisting of succinic acid, citric acid, acetic acid, malic acid, fumaric acid, stearic acid, tartaric acid, boric acid, benzoic acid, and mixtures thereof, wherein the gas generating agent is selected from the group consisting of carbonate salts, bicarbonate salts and mixture thereof, wherein the swellable water-soluble hydrophilic polymer is hypromellose, and wherein the dosage form provides an extended release of the pyridostigmine or the pharmaceutically acceptable salt thereof for at least about 14 hours. 2. The dosage form of claim 1, wherein the dosage form further comprises an immediate release layer covering at least a portion of the permeable elastic membrane, and wherein the immediate release layer comprises from about 10 mgs to about 60 mgs of pyridostigmine or a pharmaceutically acceptable salt thereof. 3. The dosage form of claim 1, wherein the core comprises from about 50 mg to about 400 mg of pyridostigmine bromide. 4. The dosage form of claim 1, wherein the dosage form, when in contact with gastric fluid, swells in about 60 minutes or less to a size that prevents its passage through pyloric sphincter. 5. The dosage form of claim 1, wherein the dosage form, when in contact with gastric fluid, floats in 30 minutes or less. 6. The dosage form of claim 4, wherein the dosage form maintains its integrity in the swollen state for a period of at least about 14 hours. 7. The dosage form of claim 1, wherein the core further includes a wicking agent. 8. The dosage form of claim 1, wherein the plasticizer is selected from the group consisting of triethyl citrate, triacetin, polyethylene glycol, propylene glycol, and dibutyl sebacate. 9. The dosage form of claim 1, wherein the dosage form is a tablet suitable for once daily administration and is administered as a single tablet/day. 10. The dosage form of claim 1, wherein the hypromellose is present in an amount of from about from about 5 wt % to about 40 wt %, based on the total weight of the core. 11. A gastroretentive dosage form comprising an immediate release layer and an extended release component; wherein the immediate release layer comprises about 10 mg to about 60 mg pyridostigmine or a pharmaceutically acceptable salt thereof; and the extended release component comprises a core, a permeable elastic membrane surrounding the core, and at least one orifice passing through the permeable elastic membrane, wherein the core comprises from about 50 mg to about 400 mg of pyridostigmine or a pharmaceutically acceptable salt thereof, a swellable water-soluble hydrophilic polymer, an acid, and a gas generating agent, wherein the permeable elastic membrane comprises a plasticizer, and a copolymer based on ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride (1:2:0.2), wherein the copolymer is present in an amount of about from 70 wt % to about 95 wt % of the membrane composition, wherein the plasticizer is present in an amount of from about 5 wt % to about 25 wt % of the membrane composition, wherein the acid is selected from the group consisting of succinic acid, citric acid, acetic acid, malic acid, fumaric acid, stearic acid, tartaric acid, boric acid, benzoic acid, and mixtures thereof, wherein the gas generating agent is selected from the group consisting of carbonate salts, bicarbonate salts and mixtures thereof, wherein the swellable water-soluble hydrophilic polymer is hypromellose, and wherein the dosage form provides an extended release of the pyridostigmine or the pharmaceutically acceptable salt thereof for at least about 14 hours. 12. The dosage form of claim 11, wherein the dosage form, when in contact with gastric fluid, swells in about 60 minutes or less to a size that prevents its passage through pyloric sphincter. 13. The dosage form of claim 11, wherein the dosage form, when in contact with gastric fluid, floats in 30 minutes or less. 14. The dosage form of claim 1, wherein the hypromellose is present in an amount of from about 5 wt % to about 40 wt %, based on the total weight of the core. 15. A gastroretentive tablet dosage form comprising a core and a permeable elastic membrane containing at least one orifice and surrounding the core, wherein the core comprises from about 50 mg to about 400 mg pyridostigmine or a pharmaceutically acceptable salt thereof, a swellable water-soluble hydrophilic polymer, an acid, and a gas-generating agent, wherein the permeable elastic membrane comprises a plasticizer, and a copolymer based on ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride (1:2:0.2), wherein the copolymer is present in an amount of from about 70 wt % to about 95 wt % of the membrane composition, wherein the plasticizer is present in an amount of from about 5 wt % to about 25 wt % of the membrane composition, wherein the acid is selected from the group consisting of succinic acid, citric acid, acetic acid, malic acid, fumaric acid, stearic acid, tartaric acid, boric acid, benzoic acid, and mixtures thereof, wherein the gas generating agent is selected from the group consisting of carbonate salts, bicarbonate salts and mixtures thereof, wherein the swellable water-soluble hydrophilic polymer is hypromellose, and wherein the tablet, comprises a long axis and a short axis, wherein the long axis is about 12 mm to about 22 mm, and the short axis is about 8 mm to about 11 mm, wherein the tablet on coming in contact with gastric fluid, swells in about 60 minutes or less to a size that prevents its passage through pyloric sphincter, and wherein the tablet provides an extended release of pyridostigmine or a pharmaceutically acceptable salt thereof for at least about 14 hours.