# US 12,178,816 B2 · Immediate release pharmaceutical formulation of 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,178,816 B2 - Document ID: US12178816B2 - Status: Granted - Kind: B2 - Application number: 18/785,063 - Filed: 2024-07-26 - Published: 2024-12-05 - Granted: 2024-12-31 - Earliest claimed: 2008-10-07 - Assignees: Kudos Pharmaceuticals Limited - Applicants: Kudos Pharmaceuticals Limited - Inventors: Michael Karl Bechtold; Julie Kay Cahill; Katja Maren Fastnacht; Kieran James Lennon; Bernd Harald Liepold; Claudia Bettina Packhaeuser; Benedikt Steitz - Web page: https://patentgrep.com/patent/US12178816B2 ## CPC - A61K 31/502: ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine - 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 9/2095: {Tabletting processes} - A61K 47/02: Inorganic compounds - A61K 47/12: Carboxylic acids; Salts or anhydrides thereof - A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids - A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} - A61P 35/00: Antineoplastic agents - 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 present invention relates to a pharmaceutical formulation comprising the drug 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one in a solid dispersion with a matrix polymer that exhibits low hygroscopicity and high softening temperature, such as copovidone. The invention also relates to a daily pharmaceutical dose of the drug provided by such a formulation. In addition, the invention relates to the use of a matrix polymer that exhibits low hygroscopicity and high softening temperature in solid dispersion with 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one for increasing the bioavailability of the drug. ## Claims ### Claim 1 An immediate-release pharmaceutical composition in the form of a tablet comprising: (a) an extrudate comprising: (i) 100 mg to 200 mg of 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one (Compound 1); (ii) at least one polymer chosen from copovidone, povidone, hypromellose phthalate, hypromellose acetate succinate, 2-hydroxypropyl-β-cyclodextrin, hypromellose, polymethacrylates, hydroxypropyl cellulose, and cellulose acetate phthalate; and (iii) at least one glidant; and (b) at least one excipient; wherein the weight ratio of Compound 1 to the at least one polymer in the extrudate is in the range of from 1:1 to 1:9; and wherein the total concentration of Compound 1 in the tablet is in the range of from 10% by weight to 35% by weight. ### Claim 2 (depends on 1) The composition of claim 1, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 3 (depends on 1) The composition of claim 1, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 4 (depends on 1) The composition of claim 1, wherein the total concentration of Compound 1 in the extrudate is in the range of from 25% by weight to 50% by weight. ### Claim 5 (depends on 4) The composition of claim 4, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 6 (depends on 4) The composition of claim 4, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 7 (depends on 1) The composition of claim 1, wherein the total concentration of the at least one polymer in the extrudate is in the range of from 50% by weight to 75% by weight. ### Claim 8 (depends on 7) The composition of claim 7, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 9 (depends on 7) The composition of claim 7, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 10 (depends on 1) The composition of claim 1, wherein the total concentration of Compound 1 in the extrudate is in the range of from 25% by weight to 50% by weight; and wherein the total concentration of the at least one polymer in the extrudate is in the range of from 50% by weight to 75% by weight. ### Claim 11 (depends on 10) The composition of claim 10, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 12 (depends on 10) The composition of claim 10, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 13 (depends on 1) The composition of claim 1, wherein the at least one glidant is colloidal silicon dioxide. ### Claim 14 (depends on 13) The composition of claim 13, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 15 (depends on 14) The composition of claim 14, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 16 (depends on 1) The composition of claim 1, wherein the total concentration of Compound 1 in the extrudate is in the range of from 25% by weight to 50% by weight; wherein the total concentration of the at least one polymer in the extrudate is in the range of from 50% by weight to 75% by weight; and wherein the at least one glidant is colloidal silicon dioxide. ### Claim 17 (depends on 16) The composition of claim 16, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 18 (depends on 16) The composition of claim 16, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 19 (depends on 1) The composition of claim 1, wherein the at least one excipient is chosen from at least one soluble filler and at least one lubricant. ### Claim 20 (depends on 19) The composition of claim 19, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 21 (depends on 19) The composition of claim 19, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 22 (depends on 1) The composition of claim 1, wherein the total concentration of Compound 1 in the extrudate is in the range of from 25% by weight to 50% by weight; wherein the total concentration of the at least one polymer in the extrudate is in the range of from 50% by weight to 75% by weight; wherein the at least one glidant is colloidal silicon dioxide; and wherein the at least one excipient is chosen from at least one soluble filler and at least one lubricant. ### Claim 23 (depends on 22) The composition of claim 22, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 24 (depends on 23) The composition of claim 23, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 25 (depends on 1) The composition of claim 1, wherein the weight ratio of Compound 1 to the at least one polymer in the extrudate is in the range of from 1:1 to 1:4. ### Claim 26 (depends on 25) The composition of claim 25, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 27 (depends on 26) The composition of claim 26, wherein the at least one polymer is a combination of copovidone and povidone. ### Claim 28 (depends on 1) The composition of claim 1, wherein the weight ratio of Compound 1 to the at least one polymer in the extrudate is in the range of from 1:1 to 1:4; wherein the at least one glidant is colloidal silicon dioxide; and wherein the at least one excipient is chosen from at least one soluble filler and at least one lubricant. ### Claim 29 (depends on 28) The composition of claim 28, wherein the at least one polymer is chosen from copovidone and povidone. ### Claim 30 (depends on 28) The composition of claim 28, wherein the at least one polymer is a combination of copovidone and povidone.