Pharmaceutical composition of a cyp11a1 inhibitor

Patent metadata

Field	Value
Publication number	US-2025099451-A1
Application number	US-202318730692-A
Country	US
Kind code	A1
Filing date	Jan 19, 2023
Priority date	Jan 20, 2022
Publication date	Mar 27, 2025
Grant date	—

Abstract

The present invention relates to a pharmaceutical composition for oral administration, particularly in the form of a tablet or a powder suitable to be filled into a capsule shell, comprising 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)-piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof as an active ingredient. Compound (I) or a pharmaceutically acceptable salt thereof is a selective inhibitor of CYP11A1 enzyme and is useful in the treatment of hormonally regulated diseases such as cancer including prostate cancer and breast cancer.

First claim

1 . A wet granulated pharmaceutical composition comprising 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof and at least one excipient.

2 . The pharmaceutical composition according to claim 1 , comprising an intragranular part which comprises at least about 5%, per weight of the intragranular part, of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof, and at least one excipient.

3 . The pharmaceutical composition according to claim 2 , wherein the intragranular part comprises from about 5% to about 20%, per weight of the intragranular part, of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof.

4 . The pharmaceutical composition according to claim 1 comprising
(a) an intragranular part comprising at least about 5%, per weight of the intragranular part, of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof, and at least one excipient; and
(b) an extragranular part comprising at least one excipient.

5 . The pharmaceutical composition according to claim 1 , comprising from about 0.5 mg to about 10 mg of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof.

6 . The pharmaceutical composition according to claim 1 , comprising
(a) an intragranular part comprising, per weight of the intragranular part, (i) from about 5% to about 20%, of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof, (ii) from about 55% to about 95% of a filler; (iii) from about 0.5% to about 10% of a disintegrant; and (iv) from about 1% to about 15% of a binder; and (b) an extragranular part comprising, per weight of the extragranular part, (i) from about 50% to 100% of a filler; (ii) from 0% to about 25% of a disintegrant; and (iii) from 0% to about 25% of a lubricant.

7 . The pharmaceutical composition according to claim 6 , wherein the filler is selected from mannitol, pregelatinized starch, microcrystalline cellulose, lactose and a calcium hydrogen phosphate.

8 . The pharmaceutical composition according to claim 6 , wherein the disintegrant comprises croscarmellose sodium or sodium starch glycolate.

9 . The pharmaceutical composition according to claim 6 , wherein the binder comprises HPMC or HPC.

10 . The pharmaceutical composition according to claim 6 , wherein the lubricant comprises sodium stearyl fumarate.

11 . The pharmaceutical composition according to claim 6 , wherein the binder comprises HPMC and the disintegrant comprises croscarmellose sodium.

12 . The pharmaceutical composition according to claim 1 , comprising
(a) an intragranular part comprising, per weight of the intragranular part, (i) from about 5% to about 20%, of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof, (ii) from about 55% to about 95% of a filler selected from mannitol, pregelatinized starch, microcrystalline cellulose, lactose, calcium hydrogen phosphate and a combination thereof; (iii) from about 0.5% to about 10% of a disintegrant selected from croscarmellose sodium, sodium starch glycolate and a combination thereof, and (iv) from about 1% to about 15% of binder comprising HPMC, HPC or combination thereof, and (b) an extragranular part comprising, per weight of the extragranular part, (i) from about 50% to 100% of a filler selected from microcrystalline cellulose, mannitol, lactose, calcium hydrogen phosphate and a combination thereof, (ii) from 0% to about 25% of a disintegrant selected from croscarmellose sodium, sodium starch glycolate and a combination thereof, and (iii) from 0% to about 25% of a lubricant comprising sodium stearyl fumarate.

13 . The pharmaceutical composition according to claim 12 , comprising
(a) an intragranular part comprising, per weight of the intragranular part, (i) from about 5% to about 20%, of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof, (ii) from about 55% to about 95% of a combination of mannitol and pregelatinized starch; (iii) from about 0.5% to about 10% of croscarmellose sodium; (iv) from about 1% to about 15% of HPMC; and (b) an extragranular part comprising, per weight of the extragranular part, (i) from about 50% to 100% of microcrystalline cellulose; (ii) from 0% to about 25% of croscarmellose sodium; and (iii) from 0% to about 25% of sodium stearyl fumarate.

14 . The pharmaceutical composition according to claim 2 , wherein the intragranular part comprises, from about 30% to about 95% per weight of the composition.

15 . The pharmaceutical composition according to claim 1 , which is in the form of a tablet, or a powder suitable to be filled into a capsule shell.

16 . The pharmaceutical composition according to claim 1 , comprising p-toluenesulfonic acid salt of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I).

17 . The pharmaceutical composition according to claim 1 , wherein the composition provides a dissolution of at least about 80% per weight of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof within 60 minutes, or within 45 minutes, in 0.05 M phosphate buffer pH 6.8 using paddle apparatus (USP apparatus 2) with paddle speed of 75 rpm at 37° C. and vessel volume of 500 ml.

18 . The pharmaceutical composition according to claim 17 , providing dissolution of at least about 80% per weight of p-toluenesulfonic acid salt of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I).

19 . The pharmaceutical composition according to claim 1 , wherein the volume median diameter (Dv50) of particles of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof is not more than 50 μm, not more than 30 μm, or not more than 25 μm.

20 . A package comprising the pharmaceutical composition according to claim 1 , together with an oxygen scavenger.

21 . A pharmaceutical composition comprising
(a) an intragranular part comprising at least about 5%, per weight of the intragranular part, of 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof, and at least one excipient; and (b) an extragranular part comprising at least one excipient.

22 . A package comprising a pharmaceutical composition comprising 2-(isoindolin-2-ylmethyl)-5-((1-(methylsulfonyl)piperidin-4-yl)methoxy)-4H-pyran-4-one (I) or a pharmaceutically acceptable salt thereof and at least one excipient, the package also comprising an oxygen scavenger.

Assignees

• Orion Corp

Inventors

• Salmia Jukka
• Singhal Mayank
• Turunen Elina

Classifications

• A61K9/4866

  Organic macromolecular compounds · CPC title

• A61K9/4858

  Organic compounds · CPC title

• A61K9/2059

  Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin · CPC title

• A61K9/2054

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/2018 Primary

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title