# US 11,298,331 B2 · Solid pharmaceutical preparation containing levothyroxine > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,298,331 B2 - Document ID: US11298331B2 - Status: Granted - Kind: B2 - Application number: 15/645,436 - Filed: 2017-07-10 - Published: 2017-10-26 - Granted: 2022-04-12 - Earliest claimed: 2012-08-20 - Assignees: Merck Patent GmbH - Applicants: Merck Patent GmbH - Inventors: Hiltrud Lindenblatt; Thomas T. Frank; Reiner Vonderschmitt - Web page: https://patentgrep.com/patent/US11298331B2 ## CPC - A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) - A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules} - A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)} - A61K 9/1658: {Proteins, e.g. albumin, gelatin} - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - A61K 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)} - A61K 9/4858: {Organic compounds} - A61K 9/50: Microcapsules {having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals (A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167)} - A61K 31/195: having an amino group - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61P 5/00: Drugs for disorders of the endocrine system - A61P 5/14: of the thyroid hormones, e.g. T3, T4 - 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 The invention relates to a solid pharmaceutical preparation comprising levothyroxine sodium, gelatine, citric acid and a filler. The solid pharmaceutical preparation has an improved stability. ## Claims ### Claim 1 A solid pharmaceutical preparation comprising levothyroxine sodium, 2-10% by weight based on the preparation of gelatine, 0.2 to 3% by weight based on the preparation of citric acid, and a filler that is 50 to 80% by weight, based on the preparation, of mannitol, sucrose or lactose, and 10 to 30% by weight, based on the preparation, of maize starch. ### Claim 2 (depends on 1) The solid pharmaceutical preparation according to claim 1, further comprising liothyronine sodium. ### Claim 3 (depends on 1) The solid pharmaceutical preparation according to claim 1, wherein the filler is sucrose. ### Claim 4 (depends on 1) The solid pharmaceutical preparation according to claim 1, wherein filler is mannitol and maize starch. ### Claim 5 (depends on 1) The solid pharmaceutical preparation according to claim 1, further comprising an antioxidant that is tocopherol, propyl gallate, tertiary butylhydroquinone, butylated hydroxyanisole or butylated hydroxytoluene. ### Claim 6 (depends on 5) The solid pharmaceutical preparation according to claim 5, wherein the antioxidant is butylated hydroxyanisole or butylated hydroxytoluene. ### Claim 7 (depends on 1) The solid pharmaceutical preparation according to claim 1, in granule, pellet, capsule or tablet form. ### Claim 8 (depends on 7) The solid pharmaceutical preparation according to claim 7, that is a tablet. ### Claim 9 (depends on 1) The solid pharmaceutical preparation according to claim 1, wherein at least one disintegrating agent is present. ### Claim 10 (depends on 9) The solid pharmaceutical preparation according to claim 9, wherein the disintegrating agent is sodium starch glycolate, carboxymethylcellulose sodium or a mixture thereof. ### Claim 11 (depends on 10) The solid pharmaceutical preparation according to claim 10, wherein the disintegrating agent present is carboxymethylcellulose sodium. ### Claim 12 (depends on 1) The solid pharmaceutical preparation according to claim 1, comprising 0.05 to 0.5% by weight butylated hydroxytoluene. ### Claim 13 (depends on 1) The solid pharmaceutical preparation according to claim 1, comprising 0.4-2% citric acid. ### Claim 14 (depends on 8) A process for the production of a solid pharmaceutical preparation according to claim 8, comprising suspending (a) levothyroxine sodium and optionally liothyronine sodium in an aqueous gelatine solution, (b) spraying the suspension obtained in (a) onto the filler in a fluidized bed granulation and drying to form granules, citric acid being either dissolved in the aqueous gelatine solution or admixed with the granules, (c) collecting the granules obtained in (b) and optionally, (d) mixing a disintegrant and optionally a lubricant with the granules obtained in (c), and (e) compressing a mixture obtained in (d) to give tablets. ### Claim 15 (depends on 14) The process for the production of a solid pharmaceutical preparation according to claim 14, wherein an antioxidant is dissolved in the aqueous gelatine solution used in (a) or is admixed with the granules in (d). ### Claim 16 (depends on 14) The process for the preparation of a solid pharmaceutical preparation according to claim 14, wherein the granules or the tablets are provided with a coating. ### Claim 17 A process for the stabilization of levothyroxine sodium, comprising adding to a composition of said levothyroxine sodium a stabilizing-effective amount of gelatine, citric acid and a filler that is sucrose, mannitol or lactose and maize starch, whereby said composition contains, by weight, based on the composition, 2-10% gelatine, 0.2-3% citric acid, 50-80% mannitol, sucrose or lactose and 10 to 30% maize starch. ### Claim 18 (depends on 17) The process according to claim 17, wherein the filler is mannitol and maize starch.