Multicomponent crystalline system comprising deferasirox and isonicotinamide and a process for the preparation thereof

Patent metadata

Field	Value
Publication number	US-9290452-B2
Application number	US-201314415875-A
Country	US
Kind code	B2
Filing date	Aug 5, 2013
Priority date	Aug 6, 2012
Publication date	Mar 22, 2016
Grant date	Mar 22, 2016

Abstract

The present invention refers to a multicomponent crystalline system (co-crystal) comprising a compound of formula (1) (4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid; INN: Deferasirox) formula (1) and a compound of formula (2) (Isonicotinamide; pyridine-4-carboxamide) formula (2), as well as to a process for obtaining the same.

First claim

The invention claimed is:

1. A multicomponent crystalline system, comprising a compound of formula 1, which is 4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid:

and a compound of formula 2, which is isonicotinamide; pyridine-4-carboxamide:

2. The multicomponent crystalline system according to claim 1 , wherein a molar ratio of the compound of formula 1 to the compound of formula 2 is from 1:0.75 to 1:1.25.

3. The multicomponent crystalline system according to claim 1 , wherein the system has an XRPD pattern with a characteristic peak, expressed in 2θ±0.2° 2θ (CuKα radiation) at 9.6, 14.6, 15.6 and/or 24.4°.

4. The multicomponent crystalline system according to claim 3 , wherein the system has an XRPD pattern with a characteristic peak, expressed in 2θ±0.2° 2θ (CuKα radiation) at 4.9, 9.6, 13.7, 14.6, 15.6, 24.4, 26.1 and/or 26.2°.

5. The multicomponent crystalline system according to claim 1 , wherein the system is suitable for treatment of iron overload in transfusion dependent anemias to reduce iron-related morbidity and mortality, for the treatment of hemochromatosis, or both.

6. A process for obtaining the crystalline composition according to claim 1 , comprising:
a) adding a compound of formula 1

in a solvent or a mixture of solvents to obtain a mixture;
b) adding a compound of formula 2

to the mixture obtained in the adding a) to form a composition;
c) optionally concentrating the composition obtained in the adding b);
d) crystallizing to obtain a suspension;
e) optionally equilibrating the obtained suspension of the crystallizing d) to obtain a precipitate; and
f) isolating the obtained precipitate.

7. The process according to claim 6 , wherein a molar ratio of the compound of formula 1 in the adding a) to the compound of formula 2 in the adding b) is from 1:0.75 to 1:5.

8. The process according to claim 6 , wherein in the adding b), the compound of formula 1 is in solid form, or as a solution in an ether, an alcohol, a ketone, an acetate, or a mixture of solvents optionally comprising water.

9. The process according to claim 6 , wherein in the crystallizing d) and/or the equilibrating, e) seed crystals are added.

10. A pharmaceutical composition comprising the multicomponent crystalline system according to claim 1 and optionally a pharmaceutically acceptable excipient.

Assignees

• Basf Se

Inventors

• Hafner Andreas
• Blatter Fritz
• Roedel Eva
• Szelagiewicz Martin
• Chiodo Tiziana
• Hintermann Tobias
• Salvador Beate
• Vossen Marcus

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07D249/08

  1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• C07D213/81 Primary

  Amides; Imides · CPC title