Claims for Patent: 12,048,695

Summary for Patent: 12,048,695

Title:	Immediate release pharmaceutical formulation of 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluoro-benzyl]-2H-phthalazin-1-one
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.
Inventor(s):	Michael Karl Bechtold, Julie Kay Cahill, Katja Maren Fastnacht, Kieran James Lennon, Bernd Harald Liepold, Claudia Bettina Packhaeuser, Benedikt Steitz
Assignee:	Abbott GmbH and Co KG, Kudos Pharmaceuticals Ltd
Application Number:	US18/312,375
Patent Claims:	1. An immediate-release pharmaceutical composition in the form of a tablet comprising: (a) a core composition comprising: a solid dispersion comprising: (i) 100 mg to 200 mg of 4-[3-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one (Compound 1); and (ii) at least one polymer chosen from copovidone, povidone, hypromellose phthalate, hypromellose acetate succinate, 2-hydroxypropyl-B-cyclodextrin, hypromellose, polymethacrylates, hydroxypropyl cellulose, and cellulose acetate phthalate; wherein the weight ratio of Compound 1 to the at least one polymer in the core composition is in the range of from 1:1 to 1:9, wherein the total concentration of Compound 1 in the core composition is in the range of from 10% by weight to 50% by weight; and (b) optionally a tablet coating; wherein release of Compound 1 from the core composition is greater than 80% as measured by reverse-phase high performance liquid chromatography (HPLC) after 120 minutes of dissolution of the core composition which had been stored in a closed high density polyethylene (HDPE) bottle with a polyethylene liner and with desiccant for 1 month at 25° C. and 60% relative humidity (RH), 3 months at 25° C. and 60% RH, 4 months at 25° C. and 60% RH, 1 month at 40° C. and 75% RH, 3 months at 40° C. and 75% RH, or 4 months at 40° C. and 75% RH, and wherein said dissolution is performed according to general procedure of the United States Pharmacopeia using Apparatus II (paddle method) in 1000 mL of a pH 6.5 phosphate buffer at a temperature of 37° C. and a stirring speed of 75 revolutions per minute. 2. The composition of claim 1, wherein the release of Compound 1 is measured after the core composition had been stored for 3 months at 25° C. and 60% RH. 3. The composition of claim 1, wherein the release of Compound 1 is measured after the core composition had been stored for 4 months at 25° C. and 60% RH. 4. The composition of claim 1, wherein the release of Compound 1 is measured after the core composition had been stored for 1 month at 40° C. and 75% RH. 5. The composition of claim 1, wherein the release of Compound 1 is measured after the core composition had been stored for 3 months at 40° C. and 75% RH. 6. The composition of claim 1, wherein the release of Compound 1 is measured after the core composition had been stored for 4 months at 40° C. and 75% RH. 7. The composition of claim 1, wherein the at least one polymer is chosen from povidone and copovidone. 8. The composition of claim 1, wherein the total concentration of Compound 1 in the core composition is 25% by weight. 9. The composition of claim 8, wherein the total concentration of the at least one polymer in the core composition is 57.5% by weight. 10. The composition of claim 1, wherein the release of Compound 1 is measured after the core composition had been stored for 1 month at 25° C. and 60% RH.