Solid form of abiraterone acetate

Patent metadata

Field	Value
Publication number	US-10045998-B2
Application number	US-201415103146-A
Country	US
Kind code	B2
Filing date	Dec 9, 2014
Priority date	Dec 12, 2013
Publication date	Aug 14, 2018
Grant date	Aug 14, 2018

Abstract

Combinations of (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate (Abiraterone acetate) with acidic substances such as citric acid, ascorbic acid, methyl-4-hydroxy benzoate, saccharin, vanillic acid, adipic acid, maleic acid, malic acid, tartaric acid are useful as pharmaceutical preparations and show improved properties such as aqueous solubility and dissolution kinetics, especially in the form of cocrystals or their combination with a suitable acid.

First claim

The invention claimed is:

1. A pharmaceutical composition, comprising:
a crystalline material or a multicomponent molecular crystal; and
a pharmaceutically acceptable carrier or diluent,
wherein the crystalline material or the multicomponent molecular crystal comprises (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate and an organic acid selected from the group consisting of, methyl-4-hydroxy benzoate, saccharin, vanillic acid, adipic acid and maleic acid, within the same crystalline phase, and
wherein, in the crystalline material or the multicomponent molecular crystal, a molar ratio of (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate to the organic acid within the same crystalline phase ranges from 2.1:1 to 1:2.1.

2. The pharmaceutical composition of claim 1 , further comprising:
at least one of citric acid and ascorbic acid as an additional component which is not part of the same crystalline phase of the crystalline material or the multicomponent molecular crystal.

3. The pharmaceutical composition of claim 1 , comprising:
a crystalline material or a multicomponent molecular crystal of (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate and an organic acid as a coformer;
wherein the coformer is methyl-4-hydroxy benzoate and the crystalline phase comprising (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate and the coformer is form A exhibiting a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 10.7, 9.2, 7.8, 5.15, 4.93, 4.84, 4.38, 3.89, and 3.28, form B exhibiting a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 5.02, 4.80, 4.72, 4.29, 4.17, 3.81, 3.59, 3.47, 3.23, and 3.02, or form C exhibiting at a temperature of 100 K a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 6.2, 15.1, 15.4, 16.8, 20.3, and 23.2;
or
the coformer is saccharin and the crystalline phase comprising (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate and the coformer exhibits a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 13.5, 10.0, 6.7, 6.5, 5.99, 5.74, 5.36, 5.05, 4.35, 4.28, 3.72, and 3.41;
or
the coformer is vanillic acid and the crystalline phase comprising (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate and the coformer exhibits a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 13.5, 6.8, 6.4, 4.51, 4.15, and 3.20;
or
the coformer is adipic acid and the crystalline phase comprising (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate and the coformer exhibits a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 9.0, 6.2, 5.63, 5.30, 4.90, 4.47, 4.07, and 3.71;
or
the coformer is maleic acid and the crystalline phase comprising (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate and the coformer is form A exhibiting a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 13.7, 10.2, 7.7, 6.6, 6.1, 5.03, 4.46, 4.26, and 3.88, form B exhibiting a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 14.1, 10.4, 7.8, 6.7, 6.2, 5.74, 5.27, 5.08, 5.04, 4.82, 4.51, 4.30, 3.91, and 3.39, form C exhibiting a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 24.0, 20.8, 10.8, 8.7, 5.61, 5.42, 5.36, 5.21, 4.95, 4.38, and 3.77, or form D exhibiting a X-ray powder diffraction pattern with the characteristic peaks, expressed in d-values (Å), at 17.2, 6.7, 6.0, 5.36, 5.08, 4.58, 4.17, and 3.59;
wherein the d-values are as detectable under standard conditions.

4. A crystalline material or multicomponent molecular crystal, comprising:
(3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate; and
an organic acid selected from the group consisting of, methyl-4-hydroxy benzoate, saccharin, vanillic acid, adipic acid, and maleic acid,
wherein (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate and the organic acid are included within the same crystalline phase, and
wherein, in the crystalline material or the multicomponent molecular crystal, a molar ratio of (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate to the organic acid within the same crystalline phase ranges from 2.1:1 to 1:2.1.

5. A process for preparing the multicomponent molecular crystal of claim 4 , comprising:
a) combining abiraterone acetate and the organic acid in a suitable solvent such that a mixture is prepared;
b) agitating the mixture; and
c) separating a solid material and drying the solid material,
wherein, the agitating optionally comprises adding seed crystals to the mixture, and
wherein, a molar ratio of (3β)-17-(pyridin-3-yl)androsta-5,16-dien-3-yl acetate to the organic acid ranges from 2.1:1 to 1:2.1.

6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is solid.

Assignees

• Basf Se

Inventors

• Chiodo Tiziana
• Salvador Beate
• Vossen Marcus
• Hafner Andreas
• Hintermann Tobias
• Szelagiewicz Martin
• Blatter Fritz
• Viertelhaus Martin
• Weishaar Walter

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61K31/58 Primary

  containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) · CPC title

• A61K9/14

  Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} · CPC title

• C07J43/003

  not condensed · CPC title