# US 2016/0113878 A1 · Stable benzimidazole formulation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2016/0113878 A1 - Document ID: US20160113878A1 - Status: Published application - Kind: A1 - Application number: 14/989,677 - Filed: 2016-01-06 - Published: 2016-04-28 - Earliest claimed: 1999-06-22 - Assignees: Dexcel Ltd. - Applicants: Dexcel Ltd. - Inventors: Raffael Lahav; Valerie Azoulay - Web page: https://patentgrep.com/patent/US20160113878A1 ## CPC - A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 9/2031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers} - A61K 9/284: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone} - A61K 9/5078: {with drug-free core} - A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A stable composition with a benzimidazole derivative, such as Omeprazole, which does not contain a separating layer between the active compound and an enteric coating layer. Instead, the enteric coating layer is applied as a solution with a pH value of at least 6.5, and more preferably in a range of from about 7 to about 10, directly to the benzimidazole derivative substrate. This solution, with the optional addition of a plasticizer, can be directly coated onto the substrate without any necessity for an intermediate layer. Furthermore, in this pH range, the enteric coating is optionally applicable in an aqueous solution, thereby obviating the need for organic solvents for dissolving the enteric coating material. The resultant formulation maintains the stability of the benzimidazole derivative during storage and at the same time protects the product during passage through the acidic environment of the stomach. ## Claims ### Claim at position 1 1-17. (canceled) ### Claim 18 A stable composition for oral administration of a benzimidazole derivative, the composition comprising: a) a single tablet core comprising a benzimidazole derivative; and b) an enteric coating on the single tablet core, wherein the enteric coating is formed from an aqueous solution or dispersion comprising an enteric coating material that has been at least about 60% neutralized by an alkaline compound prior to being applied on the single tablet core. ### Claim 19 (depends on 18) The composition of claim 18, wherein the enteric coating material has been at least about 80% neutralized by an alkaline compound. ### Claim 20 (depends on 19) The composition of claim 19, wherein the enteric coating material has been at least about 95% neutralized by an alkaline compound. ### Claim 21 (depends on 18) The composition of claim 18, wherein the aqueous solution or dispersion has a pH value of at least 6.5. ### Claim 22 (depends on 21) The composition of claim 21, wherein the pH value is in a range of from about 7 to about 10. ### Claim 23 (depends on 18) The composition of claim 18, wherein the alkaline compound comprises sodium or potassium hydroxide. ### Claim 24 (depends on 18) The composition of claim 18, wherein the alkaline compound comprises ammonium hydroxide. ### Claim 25 (depends on 18) The composition of claim 18, wherein the benzimidazole derivative is omeprazole or a pharmaceutically acceptable salt thereof. ### Claim 26 (depends on 18) The composition of claim 18, wherein the enteric coating material is selected from the group consisting of hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyvinyl acetate phthalate, cellulose acetate phthalate, cellulose acetate trimellitate, polymethacrylic acid methyl methacrylate and polymethacrylic acid ethyl methacrylate. ### Claim 27 (depends on 18) The composition of claim 18, wherein the enteric coating further comprises a plasticizer. ### Claim 28 (depends on 27) The composition of claim 27, wherein the plasticizer is selected from the group consisting of a citric acid ester and a phthalic acid ester. ### Claim 29 (depends on 18) The composition of claim 18, which is stable when stored under accelerated conditions of 30° C. and 60% relative humidity for at least 1 month. ### Claim 30 (depends on 29) The composition of claim 29, which is stable when stored under accelerated conditions of 30° C. and 60% relative humidity for at least 6 months. ### Claim 31 (depends on 18) The composition of claim 18, which has gastric acid resistance of at least 95% when placed in simulated gastric fluid at pH of about 1 for at least 2 hours. ### Claim 32 (depends on 31) The composition of claim 31, wherein the gastric resistance is maintained after storage under accelerated conditions of 30° C. and 60% relative humidity for 1 month. ### Claim 33 (depends on 32) The composition of claim 32, wherein the gastric resistance is maintained after storage under accelerated conditions of 30° C. and 60% relative humidity for 6 months.