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Brexpiprazole polymorphic forms

IP.com Disclosure Number: IPCOM000250413D
Publication Date: 2017-Jul-12

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Abstract

This disclosure relates to novel polymorphic forms of Brexpiprazole

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Brexpiprazole polymorphic forms

Brexpiprazole is chemically known as 7-[4-(4-benzo[b]thien-4-yl-1-piperazinyl) butoxy]-2(1H)-Quinolone and represented by the following chemical structure;

Formula I

The present disclosure relates to novel Brexpiprazole crystalline forms M1, M2 and M3 and these crystalline forms may be a solvates, preferably toluene, anisole and chlorobenzene solvates.

Th below table is the solvents used to prepare novel crystalline forms.

Solvent

Crystalline form

Toluene

Form-M1

Anisole

Form-M2

Chlorobenzene

Form-M3

The present disclosure also provides an amorphous premix of Brexpiprazole together with one or more pharmaceutically acceptable carriers.

Physical stability of Brexpiprazole amorphous form and amorphous premixes by spray-drying method were determined by storing the samples at 40°C/75% relative humidity (RH), at 25°C/60% relative humidity (RH) and at 5±3°C for 6 months. The product was analyzed by PXRD for final purity.

Amorphous Brexpiprazole is stable and shows no change in PXRD pattern when stored for 6 months at 5±3°C relative humidity (RH) conditions as mentioned in below Table 1.

Brexpiprazole amorphous premix with 50% Plasdone S-630 shows no change in PXRD pattern when stored for 6 months at 40°C/75%, 25°C/60% and at 5±3°C relative humidity (RH) conditions as mentioned in below Table 1.

Brexpiprazole amorphous premix with 50% Povidone K-30 shows no change in PXRD pattern when stored for 6 months at 25°C/60% and at 5±3°C relative humidity (RH) conditions and found to be physically unstable when stored at 40°C/75% relative humidity (RH) as mentioned in below Table 1.

Table 1

Condition\

Polymorph

Amorphous premix

50% w/w Plasdone S-630

Amorphous premix

50% w/w Povidone K30

Brexpiprazole amorphous form

PXRD

PXRD

PXRD

at 5± 3°C

Initial

Amorphous

Amorphous

Amorphous

15 days

Stable

Stable

Stable

1 months

Stable

Stable

Stable

2 months

Stable

Stable

Stable

3 months

Stable

Stable

Stable

6 months

Stable

Stable

Stable

at 25± 2°C / 60 ± 5 %RH

Initial

Amorphous

Amorphous

-

15 days

Stable

Stable

-

1 months

Stable

Stable

-

2 months

Stable

Stable

-

3 months

Stable

Stable

-

6 months

Stable

Stable

-

at 40 ± 2°C / 75 ± 5 %RH

Initial

Amorphous

Amorphous

-

15 days

Stable

Stable

-

1 months

Stable

Stable

-

2 months

Stable

Stable

-

3 months

Stable

Stable

-

6 months

Stable

Not Stable

-

In view of the above description and the examples below, one of ordinary skill in the art will be able to practice the invention as claimed without undue experimentation. The foregoing will be better understood regarding the following examples that detail certain procedures for the preparation of molecules, compositions and Formulations according to the present invention. All references made to these examples are for the purposes of illustration. The following examples should not be considered exhaustive, but merely illustrative of only a few of the many aspects and embodiments contemplated by the present disclosure.

Examples:

Exam...