Claims for Patent: 12,208,167

Summary for Patent: 12,208,167

Title:	Coated tablets for pH-dependent release of benzgalantamine
Abstract:	The invention relates to a pharmaceutical composition in the form of a tablet, said tablet comprising a tablet core, wherein said core comprises benzgalantamine (ALPHA-1062) or salt thereof, and an enteric coating, wherein said enteric coating is configured for dissolution at pH 5.5 and above. Further the invention relates to the pharmaceutical composition for use in the treatment of a brain disease associated with cognitive impairment and/or with a cholinergic deficit. The invention further relates to a method for preparing the pharmaceutical composition.
Inventor(s):	Michael McFadden, Denis G. Kay, Haranath Kumar Vaddi
Assignee:	Alpha Cognition Inc
Application Number:	US18/434,155
Patent Claims:	1. A pharmaceutical composition in the form of a tablet, said tablet comprising: a. a tablet core, wherein said core comprises benzgalantamine or salt thereof, and b. an enteric coating comprises a copolymer of methacrylic acid and ethyl acrylate, wherein said enteric coating is configured for dissolution at pH 5.5 and above, wherein the tablet core is coated by a film coating in direct contact with the tablet core and is coated by the enteric coating, and wherein the composition shows at most 10% dissolution of benzgalantamine under acidic stage at pH 1.2 at 120 minutes, and at least 80% release of benzgalantamine under a buffered stage at pH 5.5 or 6.8 after 60 minutes in the dissolution test according to USP 711. 2. The pharmaceutical composition according to claim 1, wherein the tablet core further comprises a water-soluble filler. 3. The pharmaceutical composition according to claim 2, wherein the water-soluble filler is mannitol. 4. The pharmaceutical composition according to claim 1, wherein the tablet core further comprises a glidant. 5. The pharmaceutical composition according to claim 4, wherein the glidant is colloidal silicon dioxide. 6. The pharmaceutical composition according to claim 1, wherein the tablet core further comprises one or more lubricants. 7. The pharmaceutical composition according to claim 6, wherein the lubricant is sodium stearyl fumarate and/or magnesium stearate. 8. The pharmaceutical composition according to claim 1, wherein the film coating comprises hydroxypropyl methylcellulose (HPMC). 9. The pharmaceutical composition according to claim 8, wherein the film coating comprises HPMC and polyethylene glycol. 10. The pharmaceutical composition according to claim 1, wherein the benzgalantamine is a gluconate salt of benzgalantamine. 11. The pharmaceutical composition according to claim 10, wherein the benzgalantamine gluconate salt is present as crystalline solid form A (anhydrous form), wherein said crystalline form has prominent peaks at 3.61, 10.98, 14.41 and 18.44 degrees 2-theta (±0.2) in a powder X-ray diffraction pattern. 12. The pharmaceutical composition according to claim 1, wherein the tablet core comprises: benzgalantamine or salt thereof in an amount (wt % of the tablet core) of 5-20%, A water-soluble filler in an amount of 60-90%, A glidant in an amount of 0.1-5%, and One or more lubricants in an amount of 0.1-5%. 13. The pharmaceutical composition according to claim 12, wherein the tablet core comprises: benzgalantamine or salt thereof in an amount (wt % of the tablet core) of 10-15%, Mannitol in an amount of 70-90%, Colloidal silicon dioxide in an amount of 0.5-2%, Sodium stearyl fumarate in an amount of 14%, and Magnesium stearate in an amount of 0.5-2%. 14. The pharmaceutical composition according to claim 1, wherein the enteric coating is present in an amount, determined by weight gain in % in addition to the tablet core, of 5-20%. 15. The pharmaceutical composition according to claim 8, wherein the film coating is present in an amount, determined by weight gain in % in addition to the tablet core, of 2-10%. 16. The pharmaceutical composition according to claim 1, wherein a. the tablet core comprises: benzgalantamine or salt thereof in an amount (wt % of the tablet core) of 10-15%, Mannitol in an amount of 70-90%, Colloidal silicon dioxide in an amount of 0.5-2%, Sodium stearyl fumarate in an amount of 1-4%, and Magnesium stearate in an amount of 0.5-2%, and b. the enteric coating is present in an amount, determined by weight gain in % in addition to the tablet core, of 7-15%, and c. a film coating is present in an amount, determined by weight gain in % in addition to the tablet core, of 3-7%, and wherein said film coating is in direct contact with the tablet core and is coated by the enteric coating. 17. The pharmaceutical composition according to claim 1, wherein the composition is configured to release benzgalantamine after administration to a subject in the small intestine of said subject at pH 5.5 and above. 18. The pharmaceutical composition according to claim 1, wherein the composition shows at most 10% dissolution of benzgalantamine in the dissolution test according to USP 711 under acidic stage (pH 1.2) and in the presence of 20% (v/v) or less ethyl alcohol after 90 minutes. 19. The pharmaceutical composition according to claim 1, wherein after administration of the composition to a subject, benzgalantamine is at negligible levels or below a lower limit of detection in the plasma of the subject (exhibits complete or nearly complete conversion of benzgalantamine to Galantamine). 20. The composition according to claim 1, wherein after administration of the composition to a subject, a. a lower maximal plasma concentration (cmax) of Galantamine is obtained compared to an immediate release galantamine reference composition, and b. an area under the plasma curve (AUC) of Galantamine is obtained at 80-125% of the AUC for the reference composition, c. wherein said immediate release galantamine reference composition is a tablet comprising no coating or a coating configured for dissolution below pH 5.5 and a molar amount of Galantamine above the molar amount of galantamine in benzgalantamine in the pharmaceutical composition. 21. The composition according to claim 1, wherein after repeated administration of the composition to a subject, a. a greater maximal plasma concentration of Galantamine at steady state (cmax,ss) is obtained compared to an extended release galantamine reference composition, and b. an area under the plasma curve (AUC) of Galantamine is obtained at 80-125% of the AUC for the reference composition, c. wherein said extended release galantamine reference composition is a solid dosage form configured for extended release of Galantamine and comprising a molar amount of Galantamine above the molar amount of galantamine in benzgalantamine in the pharmaceutical composition. 22. The composition according to claim 1, wherein after administration of the composition to a subject, the subject has a likelihood of having a gastrointestinal adverse event equal to or less than 2%. 23. A method for the treatment of a brain disease associated with cognitive impairment and/or with a cholinergic deficit, comprising administering the pharmaceutical composition according to claim 1 to a subject in need thereof. 24. The method according to claim 23, wherein the brain disease is selected from the group consisting of a brain disease with a cholinergic deficit, a brain disease with a cholinergic deficit, Alzheimer's disease, Parkinson's disease, dementia, schizophrenia, epilepsy, stroke, poliomyelitis, neuritis, myopathy, oxygen and nutrient deficiencies in the brain after hypoxia, anoxia, asphyxia, cardiac arrest, chronic fatigue syndrome, poisoning, anesthesia, spinal cord disorders, central inflammatory disorders, Lewy Body Disease, multiple sclerosis, skeletal muscle pain, autism, Rett's syndrome, motor neuron disease such as amyotrophic lateral sclerosis, traumatic brain injury, post-traumatic stress disorder, postoperative delirium, neuropathic pain, abuse of alcohol and drugs, addictive alcohol and/or nicotine craving, severe gas in the gastro-intestinal tract (GIT), constipation, low blood pressure, erratic heart rate, and effects of radiotherapy. 25. A method for preparing a pharmaceutical composition in the form of a tablet according to claim 1, wherein said composition is prepared by blending components of the tablet core to form a blend, compressing said blend to form a tablet core, coating said tablet core with a film coating, and coating said film coating with an enteric coating.