# US 11,998,640 B2 · Room temperature stable oral calcitonin formulation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,998,640 B2 - Document ID: US11998640B2 - Status: Granted - Kind: B2 - Application number: 17/675,643 - Filed: 2022-02-18 - Published: 2023-01-05 - Granted: 2024-06-04 - Earliest claimed: 2016-08-05 - Assignees: Park Therapeutics, Inc.; Enteris BioPharma, Inc. - Applicants: Park Therapeutics, Inc.; Enteris Biopharma, Inc - Inventors: James P. Gilligan; George R. Maurer; Aniruddha M. Railkar; Phillip Bauer; Thomas A. Daggs; Paul P. Shields - Web page: https://patentgrep.com/patent/US11998640B2 ## CPC - A61K 9/2886: {having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer (of the type active core-drug layer-inactive layer A61K9/209)} - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/2081: {with microcapsules or coated microparticles according to A61K9/50} - A61K 9/2846: {Poly(meth)acrylates} - A61K 9/2853: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)} - A61K 9/2893: {Tablet coating processes (mechanical aspects A61J3/06)} - A61K 38/23: Calcitonins - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 19/10: for osteoporosis - A61K 9/2095: {Tabletting processes} - 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 Room-temperature stable dosage forms for oral delivery of calcitonin are disclosed herein. Dosage forms for oral delivery of calcitonin with low water content are also disclosed herein. Further disclosed herein are methods for producing such room-temperature stable dosage forms and low-water content dosage forms. Methods of treatment comprising the administration of such room-temperature stable dosage forms and low-water content dosage forms are also disclosed herein. ## Claims ### Claim 1 A method for preparing a tablet for oral delivery of calcitonin comprising: (a) dry blending calcitonin, silicified microcrystalline cellulose, coated citric acid, copovidone, crospovidone, and magnesium stearate; (b) compressing the blended mixture into a tablet core; (c) applying a water-soluble barrier layer in an initial spray at a first spray rate sufficient to add approximately 0.25% (w/w) to the tablet core in about 30 minutes at an average product temperature of at least 45° C.; and (d) applying an enteric coating. ### Claim 2 A method for spray coating a tablet core for oral delivery of calcitonin comprising: (a) providing a tablet core; (b) applying a water-soluble barrier layer in an initial spray at a first spray rate sufficient to add approximately 0.25% (w/w) of the water-soluble barrier layer to the tablet core in about 30 minutes at an average product temperature of at least 45° C.; and (c) applying an enteric coating. ### Claim 3 (depends on 2) The method of claim 2, wherein the tablet core comprises (a) calcitonin intermixed with coated citric acid particles, (b) crospovidone; (c) copovidone; (d) microcrystalline cellulose; and (e) magnesium stearate. ### Claim 4 (depends on 3) The method of claim 3, wherein the microcrystalline cellulose is silicified microcrystalline cellulose. ### Claim 5 (depends on 1) The method of claim 1, wherein the tablet core comprises (a) about 0.01% (w/w) to about 0.10% (w/w) salmon calcitonin; (b) about 62% (w/w) maltodextrin-coated citric acid; (c) about 1.1% (w/w) crospovidone; (d) about 5% (w/w) copovidone; (e) about 31% (w/w) silicified microcrystalline cellulose; and (f) about 0.5% (w/w) magnesium stearate. ### Claim 6 (depends on 5) The method of claim 5, wherein the tablet core comprises about 0.02% (w/w) salmon calcitonin. ### Claim 7 (depends on 1) The method of claim 1, wherein the first spray rate is sufficient to add approximately 0.5% (w/w) of the water-soluble barrier layer to the tablet core in about 30 minutes. ### Claim 8 (depends on 1) The method of claim 1, wherein after applying the water-soluble barrier layer at the first spray rate for at least 30 minutes, the water-soluble barrier layer is applied in a subsequent spray at a second spray rate, which is faster than the first spray rate. ### Claim 9 (depends on 8) The method of claim 8, wherein the second spray rate is sufficient to add about 5.5% (w/w) of the water-soluble barrier layer to the tablet core in about two hours to about four and a half hours. ### Claim 10 (depends on 8) The method of claim 8, wherein the method comprises applying the water-soluble barrier layer at the first spray rate until about 0.5% (w/w) to about 2.0% (w/w) of the water-soluble barrier layer is added to the tablet core and then applying the water-soluble barrier layer at the second spray rate. ### Claim 11 (depends on 10) The method of claim 10, wherein the water-soluble barrier layer is applied at the second spray rate until a total of about 3.0% (w/w) to about 7.0% (w/w) of the water-soluble barrier layer is added to the tablet core. ### Claim 12 (depends on 2) The method of claim 2, wherein the average product temperature during the initial spray is at least 46° C. to at least 50° C. ### Claim 13 (depends on 1) The method of claim 1, wherein the minimum product temperature during the initial spray is at least 45° C. ### Claim 14 (depends on 1) The method of claim 1, wherein the enteric coating adds about 6% to about 8% to the weight of the tablet, including the tablet core and the water-soluble barrier layer. ### Claim 15 (depends on 2) The method of claim 2, wherein after applying the water-soluble barrier layer at the first spray rate for at least 30 minutes, the water-soluble barrier layer is applied in a subsequent spray at a second spray rate, which is faster than the first spray rate. ### Claim 16 (depends on 15) The method of claim 15, wherein the second spray rate is sufficient to add about 5.5% (w/w) of the water-soluble barrier layer to the tablet core in about two hours to about four and a half hours. ### Claim 17 (depends on 15) The method of claim 15, wherein the method comprises applying the water-soluble barrier layer at the first spray rate until about 0.5% (w/w) to about 2.0% (w/w) of the water-soluble barrier layer is added to the tablet core and then applying the water-soluble barrier layer at the second spray rate. ### Claim 18 (depends on 17) The method of claim 17, wherein the water-soluble barrier layer is applied at the second spray rate until a total of about 3.0% (w/w) to about 7.0% (w/w) of the water-soluble barrier layer is added to the tablet core. ### Claim 19 (depends on 2) The method of claim 2, wherein the average product temperature during the initial spray is at least 46° C. to at least 50° C. ### Claim 20 (depends on 2) The method of claim 2, wherein the minimum product temperature during the initial spray is at least 45° C.