Claims for Patent: 12,042,559

Summary for Patent: 12,042,559

Title:	Gastroretentive dosage forms for sustained drug delivery
Abstract:	The present disclosure is directed to floating gastroretentive dosage forms with prolonged gastric residence time. The disclosure also provides rapidly expanding sustained release or combined immediate release and sustained release formulations comprising drugs that require targeted release in the proximal gastrointestinal tract for maximum therapeutic benefit. The rapidly expanding floating gastroretentive dosage forms comprise a permeable elastic membrane providing desired characteristics for drug release and mechanical strength to maintain tablet integrity.
Inventor(s):	Kanji Meghpara, Jaydeep Vagashiya, Navnit H. Shah, Dipen Desai, Wantanee Phuapradit, Harpreet Kaur Sandhu, Siva Ram Kiran Vaka, Namdev B. Shelke, Ashish Chatterji
Assignee:	Amneal Complex Products Research LLC
Application Number:	US18/231,449
Patent Claims:	1. A gastroretentive tablet dosage form comprising: a) a tablet core comprising pyridostigmine bromide, a swellable water-soluble hydrophilic polymer, and a gas-generating agent, and b) a coating of water-insoluble permeable elastic membrane comprising an orifice, wherein the coating surrounds the tablet core, and wherein the water-insoluble permeable elastic membrane comprises a plasticizer, and a copolymer of ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride. 2. The dosage form of claim 1, wherein the plasticizer is selected from the group consisting of triethyl citrate, triacetin, polyethylene glycol, propylene glycol, and mixtures thereof. 3. The dosage form of claim 1, wherein the plasticizer is present in an amount of from about 5% wt/wt to about 20% wt/wt, based on a total weight of the copolymer and the plasticizer. 4. The dosage form of claim 1, wherein the gas generating agent is present in an amount of from about 10% wt/wt to about 25% wt/wt, based on a total weight of the tablet core. 5. The dosage form of claim 1, wherein the tablet 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 1, wherein the dosage form exhibits at least about 20% dissolution of pyridostigmine bromide in 900 ml of 50 mM pH 4.5 acetate buffer, measured using USP Apparatus I (custom basket) at 100 rpm. 7. The dosage form of claim 1, wherein the dosage form provides extended release of pyridostigmine bromide for at least about 12 hours in 900 ml of 50 mM pH 4.5 acetate buffer, measured using USP Apparatus I (custom basket) at 100 rpm. 8. The dosage form of claim 1, wherein the tablet core further comprises a superdisintegrant selected from the group consisting of crospovidone; croscarmellose sodium; sodium starch glycolate; low substituted hydroxypropyl cellulose; microcrystalline cellulose; alginic acid; a mixture of mannitol, crospovidone, and polyvinyl acetate; a mixture of mannitol, starch, croscarmellose sodium, silica, and colloidal silica; and mixtures thereof. 9. The dosage form of claim 1, wherein the swellable water-soluble hydrophilic polymer in the tablet core is selected from the group consisting of hypromellose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, a polyethylene oxide polymer, and sodium alginate. 10. The dosage form of claim 1, wherein the gas-generating agent is selected from the group consisting of sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium carbonate, and mixtures thereof. 11. A gastroretentive tablet dosage form comprising: a) a tablet core comprising pyridostigmine bromide, a swellable water-soluble hydrophilic polymer, and a gas-generating agent, b) a coating of water-insoluble permeable elastic membrane comprising an orifice, and c) an immediate release layer comprising pyridostigmine bromide, wherein the coating surrounds the tablet core, wherein the immediate release layer surrounds the coating such that the coating is between the tablet core and the immediate release layer, and wherein the water-insoluble permeable elastic membrane comprises a plasticizer, and a copolymer of ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride. 12. The dosage form of claim 11, wherein the plasticizer is selected from the group consisting of triethyl citrate, triacetin, polyethylene glycol, propylene glycol, and mixtures thereof. 13. The dosage form of claim 11, wherein the plasticizer is present in an amount of from about 5% wt/wt to about 20% wt/wt, based on a total weight of the copolymer and the plasticizer. 14. The dosage form of claim 11, wherein the gas generating agent is present in an amount of from about 10% wt/wt to about 25% wt/wt, based on a total weight of the tablet core. 15. The dosage form of claim 11, wherein the tablet 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. 16. The dosage form of claim 11, wherein the dosage form provides extended release of pyridostigmine bromide for at least about 12 hours in 900 ml of 50 mM pH 4.5 acetate buffer, measured using USP Apparatus I (custom basket) at 100 rpm. 17. The dosage form of claim 11, wherein the swellable water-soluble hydrophilic polymer in the tablet core is selected from the group consisting of hypromellose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, microcrystalline cellulose, a polyethylene oxide polymer, and sodium alginate. 18. The dosage form of claim 11, wherein the gas-generating agent is selected from the group consisting of sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium carbonate, and mixtures thereof. 19. A method for improving bioavailability of drugs with narrow absorption window in the proximal gastrointestinal (GI) tract comprising administering a gastroretentive tablet dosage form comprising: a) a tablet core comprising a drug with narrow absorption window in the upper GI trat tract, a swellable water-soluble hydrophilic polymer, and a gas-generating agent, and b) a coating of water-insoluble permeable elastic membrane comprising an orifice, wherein the coating surrounds the tablet core, and wherein the water-insoluble permeable elastic membrane comprises a plasticizer, and a copolymer of ethyl acrylate, methyl methacrylate, and trimethylammonioethyl methacrylate chloride. 20. The method of claim 19, wherein the dosage form-further comprises an immediate release layer comprising a second drug with narrow absorption window in the upper GI tract, wherein the second drug in the immediate release layer is same as the drug in the tablet core.