Claims for Patent: 11,666,536

Summary for Patent: 11,666,536

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):	Siva Ram Kiran Vaka, Dipen Desai, Wantanee Phuapradit, Navnit H. Shah, Namdev B. Shelke
Assignee:	Amneal Complex Products Research LLC
Application Number:	US17/550,117
Patent Claims:	1. A gastroretentive dosage form comprising a core, and a permeable elastic membrane comprising at least one orifice and surrounding the core, wherein the core comprises pyridostigmine or a pharmaceutically acceptable salt thereof, a gas-generating agent, and a swellable water-soluble hydrophilic polymer, wherein the permeable elastic membrane comprises a copolymer based on ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride, and wherein the copolymer is present in an amount of from about 70 wt % to about 95 wt %, based on the total weight of the membrane. 2. The dosage form of claim 1, wherein the core further comprises a wicking agent selected from the group consisting of crospovidone; croscarmellose sodium; sodium starch glycolate; low-substituted hydroxypropyl cellulose; a mixture of mannitol, crospovidone, and polyvinyl acetate; a coprocessed blend of mannitol, starch, crospovidone, croscarmellose sodium, colloidal silica, and silica; microcrystalline cellulose; alginic acid; and mixtures thereof. 3. The dosage form of claim 2, wherein the wicking agent is crospovidone. 4. The dosage form of claim 2, wherein the wicking agent is present in an amount of from about 5 wt % to about 25 wt %, based on the total weight of the core. 5. The dosage form of claim 1, wherein the core further comprises an acid 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. 6. The dosage form of claim 5, wherein the acid is succinic acid. 7. The dosage form of claim 5, wherein the acid is present in an amount of from about 0 wt % to about 20 wt %, based on the total weight of the core. 8. The dosage form of claim 1, wherein the gas generating agent is selected from the group consisting of carbonate salts and bicarbonate salts of alkali and alkaline earth metals. 9. The dosage form of claim 1, wherein the gas generating agent is selected from the group consisting of sodium bicarbonate, sodium carbonate, magnesium carbonate, and/or calcium carbonate, and mixtures thereof. 10. The dosage form of claim 9, wherein the gas generating agent is a mixture of sodium bicarbonate and calcium carbonate. 11. The dosage form of claim 1, wherein the gas generating agent is present in an amount of from about 5 wt % to about 50 wt %, based on the total wt of the core. 12. The dosage form of claim 1, wherein the core further comprises a glidant selected from the group consisting of talc, colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, tribasic calcium phosphate, and mixtures thereof. 13. The dosage form of claim 12, wherein the glidant is present in an amount of from about 0.1 wt % to about 2 wt %, based on the total weight of the core. 14. The dosage form of claim 1, wherein the swellable water-soluble hydrophilic polymer is selected from the group consisting of hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose, a polyethylene oxide polymer, a carbomer, sodium alginate, and mixtures thereof. 15. The dosage form of claim 14, wherein the swellable water-soluble hydrophilic polymer is hydroxypropyl methylcellulose. 16. The dosage form of claim 14, wherein the swellable water-soluble hydrophilic polymer is a mixture of two hydroxypropyl methylcellulose polymers with different viscosities. 17. The dosage form of claim 15 wherein the hydroxypropyl methylcellulose is present in an amount of from about 5 wt % to about 35 wt %, based on the total weight of the core. 18. The dosage form of claim 1, wherein the core comprises from about 50 mg to about 400 mg of pyridostigmine or a pharmaceutically acceptable salt thereof. 19. The dosage form of claim 1, wherein the core further comprises mannitol. 20. The dosage form of claim 19, wherein the mannitol is present in an amount of from about 1 wt % to about 40 wt %, based on the total weight of the core. 21. The dosage form of claim 1, wherein the permeable elastic membrane further comprises a plasticizer selected from the group consisting of triethyl citrate, triacetin, polyethylene glycol, propylene glycol, dibutyl sebacate, and mixtures thereof. 22. The dosage form of claim 21, wherein the plasticizer is present in an amount of from about 5 wt % to about 25 wt %, based on the total weight of the membrane composition. 23. The dosage form of claim 21, wherein the membrane further comprises an anti-tacking agent selected from the group consisting of talc, colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, tribasic calcium phosphate, or mixtures thereof. 24. The dosage form of claim 23, wherein the anti-tacking agent is present in an amount of from about 5 wt % to about 30 wt % of the membrane composition. 25. The dosage form of claim 1, wherein the dosage form further comprises an immediate release drug layer comprising pyridostigmine or a pharmaceutically acceptable salt thereof. 26. The dosage form of claim 25, wherein the immediate release drug layer comprises from about 10 mg to about 100 mg of pyridostigmine or a pharmaceutically acceptable salt thereof. 27. The dosage form of claim 1, wherein the dosage form further comprises a seal coat between the core and the permeable elastic membrane. 28. The dosage form of claim 27, wherein the seal coat comprises a water-soluble polymer selected from the group consisting of polyvinyl alcohol, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and mixtures thereof. 29. A gastroretentive dosage form comprising an immediate release portion and an extended release portion, wherein the immediate release portion comprises an immediate release drug layer comprising pyridostigmine or a pharmaceutically acceptable salt thereof, wherein the extended release portion comprises a core, and a permeable elastic membrane comprising at least one orifice and surrounding the core, wherein the core comprises pyridostigmine or a pharmaceutically acceptable salt thereof, a gas-generating agent, and a swellable water-soluble hydrophilic polymer, wherein the immediate release drug layer surrounds the core, wherein the permeable elastic membrane comprises a copolymer based on ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride, and wherein the copolymer is present in an amount of from about 70 wt % to about 95 wt %, based on the total weight of the membrane. 30. The dosage form of claim 29, wherein the core further comprises an acid 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. 31. The dosage form of claim 29, wherein the core further comprises a wicking agent selected from the group consisting of crospovidone; croscarmellose sodium; sodium starch glycolate; low-substituted hydroxypropyl cellulose; a mixture of mannitol, crospovidone, and polyvinyl acetate; a coprocessed blend of mannitol, starch, crospovidone, croscarmellose sodium, colloidal silica, and silica; microcrystalline cellulose; alginic acid; and mixtures thereof. 32. The dosage form of claim 29, wherein the permeable elastic membrane further comprises a plasticizer selected from the group consisting of triethyl citrate, triacetin, polyethylene glycol, propylene glycol, dibutyl sebacate, and mixtures thereof. 33. A method of treating Myasthenia Gravis, the method comprising orally administering to a person in need thereof an extended release gastroretentive dosage form comprising pyridostigmine or a pharmaceutically acceptable salt thereof, wherein the dosage form comprises a core comprising pyridostigmine or a pharmaceutically acceptable salt thereof and a permeable elastic membrane comprising at least one orifice and surrounding the core, wherein the core comprises pyridostigmine or a pharmaceutically acceptable salt thereof, wherein the permeable elastic membrane comprises a copolymer based on ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride, and wherein the copolymer is present in an amount of from about 70 wt % to about 95 wt %, based on the total weight of the membrane. 34. A method of treating nerve gas poisoning or injuries, the method comprising orally administering to a person in need thereof an extended release gastroretentive dosage form comprising pyridostigmine or a pharmaceutically acceptable salt thereof, wherein the dosage form comprises a core comprising pyridostigmine or a pharmaceutically acceptable salt thereof and a permeable elastic membrane comprising at least one orifice and surrounding the core, wherein the core comprises pyridostigmine or a pharmaceutically acceptable salt thereof, wherein the permeable elastic membrane comprises a copolymer based on ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride, and wherein the copolymer is present in an amount of from about 70 wt % to about 95 wt %, based on the total weight of the membrane.