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A crystalline form of bosentan

IP.com Disclosure Number: IPCOM000185691D
Publication Date: 2009-Jul-31
Document File: 2 page(s) / 126K

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure relates to a solid form of bosentan and a crystallization process for its preparation

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The present disclosure relates to a solid form of bosentan and a crystallization process for its preparation

A three-neck 100 ml flask was charged with 10.0 g of bosentan, 15 ml of methanol and 15 ml of isopropyl acetate. The resulting suspension was heated to reflux (64-66ºC) resulting in complete dissolution. The solution was allowed to cool to 25 ºC, causing precipitation and the resulting suspension was further cooled to 0-5 ºC and stirred for 2 hours. The precipitate was suction-filtered and washed twice with 2 ml of methanol. The solid was dried under vacuum at 50 ºC to obtain 9.6 g of yellow crystals (yield 96%, HPLC purity 98.3%).

The product was analysed by powder X-ray diffraction, see Figure 1 and Table 1 below.

Figure 1: X-ray powder diffractogram for Bosentan Form X

 

Peak Number

Pos [°2-Theta]

d-spacing [Å]

Height [counts]

Rel. Int. [%]

1

7.72

11.40

4571

44.2

2

9.18

9.60

2731

25.5

3

9.66

9.20

7537

74.3

4

10.25

8.60

3321

31.5

5

11.79

7.50

2084

18.9

6

12.07

7.30

2007

18.2

7

13.71

6.50

1319

11.2

8

15.30

5.80

6343

62.2

9

15.52

5.70

10064

100.0

10

16.41

5.40

2197

20.1

11

16.62

5.30

2811

26.3

12

18.14

4.90

3866

37.0

13

18.40

4.80

5532

54.0

14

18.62

4.80

2965

27.9

15

19.43

4.60

1778

15.8

16

19.84

4.50

2325

21.4

17

20.15

4.40

1500

13.0

18

21.00

4.20

5287

51.5

19

21.38

4.20

1646

14.5

20

21.63

4.10

4760

46.1

21

22.12

4.00

2687

25.1

22

23.09

3.80

1290

10.9

23

23.18

3.80

1674

14.8

24

23.77

3.70

3275

31.0

25

24.55

3.60

1265

10.6

26

24.74

3.60

2241

20.5

27

25.02

3.60

2737

25.6

28

26.62

3.30

1295

10.9

29

26.96

3.30

1691

14.9

30

27.17

3.30

1439

12.4

31

27.35

3.30

2052

18.6

32

29.05

3.10

1224

10.2

Table 1: X-Ray powder diffraction peak listing for Bosentan Form X

 

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