Polymorphic forms and process
The present invention relates to a polymorph of a compound of formula (I) This polymorph is particularly suitable in treating IPF by pulmonary administration.
1. A polymorph of a compound of formula (I)
wherein the polymorph is 3,3′-Dideoxy-3,3′-bis-[4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl]-1,1′-sulfanediyl-di-β-D-galactopyranoside and wherein:
the polymorph has a polymorphic form 1 as identified in the following XRPD diffractogram peak list:
No.
Pos. [°2Th.]
Rel. Int. [%]
1
7.1269
77.72
2
7.5067
56
3
10.125
36.86
4
14.3791
32.28
5
15.0846
18.59
6
15.8201
35.78
7
16.7088
78.1
8
18.6001
21.29
9
19.7777
100
10
20.3353
57.04
11
21.7744
79.92
12
22.6053
35.8
13
23.4305
45.78
14
24.3658
51.03
15
25.8091
54.36
16
26.7046
25.38
17
29.028
16.19
18
30.2989
28.02
19
32.2693
14.86
20
33.5132
11.55
21
34.6078
11.54
22
35.8435
9.6
23
44.6257
22.73;
or
the polymorph has a polymorphic form 1 as identified in the XRPD diffractogram in FIG. 1 .
2. The polymorph of claim 1 , wherein the polymorph is a hydrate.
3. The polymorph of claim 2 , wherein the hydrate contains 3-5% by weight water.
4. The polymorph of claim 1 , wherein the polymorph is micronized.
5. The polymorph of claim 4 , wherein the polymorph is micronized to a size that can reach the bronchioles and/or the alveoli of the human.
6. A pharmaceutical composition comprising the polymorph of claim 1 , and optionally a pharmaceutically acceptable additive.
7. A process of making the polymorph of claim 1 comprising:
suspending or dissolving 3,3′-Dideoxy-3,3′-bis-[4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl]-1,1′-sulfanediyl-di-β-D-galactopyranoside in an organic solvent; and then
making polymorphic form 1 by temperature cycling, crash cooling, evaporation, or a combination thereof.
8. A method for treatment of pulmonary fibrosis in a human comprising administering to the lung tissue of the human an amount of the polymorph of claim 1 effective to treat said pulmonary fibrosis.
9. The method of claim 8 , wherein the administration is carried out by a dry powder inhaler.
10. The method of claim 9 , wherein the administration is carried out by a monodose dry powder inhaler.
11. The method of claim 8 , wherein the polymorph is administered to the bronchioles and/or the alveoli of the human.
12. The method of claim 8 , wherein the amount is a once daily amount from 0.15 mg to 50 mg.
13. The method of claim 12 , wherein the amount is a once daily amount selected from the group consisting of: 0.15 mg to 0.50 mg, 0.50 mg to 0.75 mg, 0.75 mg to 1.25 mg, 1.25 mg to 1.5 mg, 1.5 mg to 1.75 mg, 1.75 mg to 2 mg, 2 mg to 2.25 mg, 2.25 mg to 2.5 mg, 2.5 mg to 2.75 mg, 2.75 mg to 3 mg, 3 mg to 5 mg, 5 mg to 7 mg, 7 mg to 8 mg, 8 mg to 10 mg, 10 mg to 20 mg and 20 mg to 50 mg.
14. A method for treatment of pulmonary fibrosis in a human comprising administering to the lung tissue of the human an amount of the polymorph of claim 2 effective to treat said pulmonary fibrosis.
15. A method for treatment of pulmonary fibrosis in a human comprising administering to the lung tissue of the human an amount of the polymorph of claim 3 effective to treat said pulmonary fibrosis.
16. A method for treatment of pulmonary fibrosis in a human comprising administering to the lung tissue of the human an amount of the polymorph of claim 4 effective to treat said pulmonary fibrosis.
17. A method for treatment of pulmonary fibrosis in a human comprising administering to the lung tissue of the human an amount of the polymorph of claim 5 effective to treat said pulmonary fibrosis.