# US 2021/0330665 A1 · Pharmaceutical formulations > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0330665 A1 - Document ID: US20210330665A1 - Status: Published application - Kind: A1 - Application number: 17/237,201 - Filed: 2021-04-22 - Published: 2021-10-28 - Earliest claimed: 2020-04-24 - Assignees: AstraZeneca AB - Applicants: AstraZeneca AB - Inventors: Farhan Abdel Karim Mohammad AL HUSBAN - Web page: https://patentgrep.com/patent/US20210330665A1 ## CPC - A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) - A61K 9/2009: {Inorganic compounds} - A61K 9/2013: {Organic compounds, e.g. phospholipids, fats} - A61K 9/2027: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin} - A61K 9/2077: {Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets} - A61K 9/2095: {Tabletting processes} - A61K 9/284: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone} - A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/485: {Inorganic compounds} - A61K 9/4858: {Organic compounds} - A61K 9/4866: {Organic macromolecular compounds} - 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) ## Abstract The present specification relates to pharmaceutical formulations comprising N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine, microcrystalline cellulose (MCC) and dicalcium phosphate anhydrous (DCPA), for example tablets with immediate release properties. ## Claims ### Claim 1 A pharmaceutical formulation comprising N-(1-(3-fluoropropyl)-azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine, microcrystalline cellulose, and dicalcium phosphate anhydrous. ### Claim 2 (depends on 1) The pharmaceutical formulation of claim 1, wherein the formulation is an immediate release pharmaceutical formulation. ### Claim 3 (depends on 1) The pharmaceutical formulation of claim 1, wherein the amount of N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine is up to 60% w/w. ### Claim 4 (depends on 1) The pharmaceutical formulation of claim 1, wherein the amount of N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine is 27% w/w. ### Claim 5 (depends on 1) The pharmaceutical formulation of claim 1, wherein the ratio of microcrystalline cellulose to dicalcium phosphate anhydrous is from 3:1 to 2:3. ### Claim 6 (depends on 1) The pharmaceutical formulation of claim 1, wherein the ratio of microcrystalline cellulose to dicalcium phosphate anhydrous is from 3:1 to 3:2. ### Claim 7 (depends on 1) The pharmaceutical formulation of claim 1, wherein the combined amount of microcrystalline cellulose and dicalcium phosphate anhydrous is from 15% w/w to 85% w/w. ### Claim 8 (depends on 1) The pharmaceutical formulation of claim 1, wherein the combined amount of microcrystalline cellulose and dicalcium phosphate anhydrous is from 40% w/w to 85% w/w. ### Claim 9 (depends on 1) The pharmaceutical formulation of claim 1, further comprising at least one additional disintegrant in an amount of up to 10% w/w, optionally wherein the disintegrant is selected from croscarmellose sodium, crospovidine, and sodium starch glycolate. ### Claim 10 (depends on 9) The pharmaceutical formulation of claim 9, wherein the at least one additional disintegrant is sodium starch glycolate. ### Claim 11 (depends on 9) The pharmaceutical formulation of claim 9, wherein the at least one additional disintegrant is present in an amount of up to 5% w/w. ### Claim 12 (depends on 1) The pharmaceutical formulation of claim 1, further comprising at least one lubricant in an amount of up to 4% w/w, optionally wherein the disintegrant is selected from magnesium stearate, calcium stearate, and sodium stearyl fumarate. ### Claim 13 (depends on 12) The pharmaceutical formulation of claim 12, wherein the at least one lubricant is magnesium stearate. ### Claim 14 (depends on 12) The pharmaceutical formulation of claim 12, wherein the at least one lubricant is present in an amount of up to 1.5% w/w. ### Claim 15 (depends on 1) The pharmaceutical formulation of claim 1 in the form of a tablet, optionally wherein the tablet is coated. ### Claim 16 (depends on 15) The tablet of claim 15, wherein the tablet contains 25 mg, 50 mg or 100 mg of N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine. ### Claim 17 (depends on 1) The pharmaceutical formulation of claim 1 in the form of a capsule. ### Claim 18 (depends on 15) A process for manufacturing the tablet of claim 15 comprising the steps of: i) dry granulating N-(1-(3-fluoropropyl)azetidin-3-yl)-6-((6S,8R)-8-methyl-7-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-3H-pyrazolo[4,3-f]isoquinolin-6-yl)pyridin-3-amine with microcrystalline cellulose and dicalcium phosphate anhydrous to form a blend; and ii) compressing the blend into the tablet. ### Claim 19 (depends on 18) The process of claim 18 wherein the compression into tablets is performed by roller compaction. ### Claim 20 (depends on 18) The process of claim 18, wherein the process is a continuous direct compression process. ### Claim 21 (depends on 2) The pharmaceutical formulation of claim 2 wherein: the combined amount of microcrystalline cellulose and dicalcium phosphate anhydrous is from 40% w/w to 85% w/w; and the ratio of microcrystalline cellulose to dicalcium phosphate anhydrous is from 3:1 to 3:2. ### Claim 22 (depends on 21) The pharmaceutical formulation of claim 21, wherein the formulation further comprises at least one disintegrant in an amount of up to 5% w/w. ### Claim 23 (depends on 22) The pharmaceutical formulation of claim 22, wherein the disintegrant is selected from croscarmellose sodium, crospovidine, and sodium starch glycolate. ### Claim 24 (depends on 22) The pharmaceutical formulation of claim 22, wherein the formulation further comprises at least one lubricant in an amount of up to 1.5% w/w. ### Claim 25 (depends on 24) The pharmaceutical formulation of claim 24, wherein the at least one lubricant is selected from magnesium stearate, calcium stearate, and sodium stearyl fumarate. ### Claim 26 (depends on 2) The pharmaceutical formulation of claim 2, wherein: the combined amount of microcrystalline cellulose and dicalcium phosphate anhydrous is from 40% w/w to 85% w/w; the ratio of microcrystalline cellulose to dicalcium phosphate anhydrous is from 3:1 to 3:2; the formulation further comprises at least one disintegrant in an amount of up to 5% w/w, wherein the disintegrant is selected from croscarmellose sodium, crospovidine, and sodium starch glycolate; and the formulation further comprises at least one lubricant in an amount of up to 1.5% w/w, wherein the at least one lubricant is selected from magnesium stearate, calcium stearate, and sodium stearyl fumarate. ### Claim 27 (depends on 26) The pharmaceutical formulation of claim 26 in the form of a tablet. ### Claim 28 (depends on 27) The tablet of claim 27, wherein the tablet is coated.