Polymorphic form of montelukast sodium
View Patent ↗The invention provides novel polymorphic form of montelukast sodium, as well as methods of using and pharmaceutical compositions containing saud novel form. Also provided are montelukast sodium: acetonitrile solvates, which are intermediates in the formation of crystalline montelukast sodium.
1. Form B montelukast sodium characterized as having an x-ray powder diffraction pattern peak position substantially as shown:
2 θ
d spacing (A)
Intensity
5.4
16.4
s
5.7
15.6
vs
9.5
9.3
m
10.4
8.5
m
17.1
5.2
s
18.7
4.73
s
21.6
4.11
s.
2. Montelukast sodium:acetonitrile monosolvate.
3. Montelukast sodium:acetonitrile monosolvate of claim 2 characterized by having 13 C solid-state CPMAS NMR chemical shifts in ppm at 72 (sharp triplet), 74 (sharp triplet), 77 (sharp triplet), 179 (sharp doublet), and 182 (sharp doublet).
4. Montelukast sodium:acetonitrile monosolvate of claim 2 further characterized by having X-ray powder diffraction peaks substantially as shown:
2 θ
d spacing (Å)
Intensity
4.30
20.5
vs
5.9
14.9
s
6.2
14.3
s
6.8
13.0
w
7.3
12.0
w
10.5
8.4
m
11.0
8.0
w
12.7
7.0
m
16.2
5.5
s
18.1
4.90
w
18.7
4.74
w
21.6
4.12
w
23.4
3.80
w
23.9
3.72
w.
5. Montelukast sodium:acetonitrile hemisolvate.
6. Montelukast sodium:acetonitrile hemisolvate of claim 4 characterized by having 13 C solid-state CPMAS NMR chemical shifts in ppm at 27 (well resolved) and 55 (well resolved), referenced by setting the carbonyl resonance of glycine to 176.08.
7. Montelukast sodium:acetonitrile hemisolvate of claim 4 characterized by having X-ray powder diffraction peaks substantially as shown:
2 θ
d spacing (Å)
Intensity
4.57
19.3
s
5.3
16.7
s
5.6
15.7
vs
6.5
13.6
m
9.4
9.4
m
10.3
8.6
w
11.6
7.6
m
14.1
6.3
w
14.5
6.1
m
15.1
5.8
w
16.2
5.5
m
17.0
5.2
m
18.5
4.79
s
20.8
4.26
m
21.3
4.17
s.
8. A method for the preparation of montelukast sodium Form A substantially free of amorphous montelukast sodium comprising: 1) collecting montelukast sodium:acetonitrile monosolvate; and 2) removing acetonitrile from the collected monosolvate.
9. A method for the preparation of montelukast sodium Form A substantially free of amorphous montelukast sodium comprising: 1) contacting amorphous montelukast sodium or a mixture of amorphous montelukast sodium and montelukast sodium Form A with acetonitrile to form montelukast sodium:acetonitrile monosolvate; 2) collecting said monosolvate; and 3) removing acetonitrile from the collected monosolvate.
10. The method of claim 8 wherein a mixture of amorphous montelukast sodium and montelukast sodium Form A is used in step 1).