Solid state forms of Ensifentrine and process for preparation thereof
The present disclosure encompasses solid state forms of Ensifentrine, in embodiments crystalline polymorphs or salts of Ensifentrine, particularly Ensifentrine ethane-1.2-disulfonate, processes for preparation thereof, and pharmaceutical compositions thereof.
1 . Crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate characterized by data selected from at least one of:
a) an XRPD pattern having peaks at 14.4, 19.0, 19.7, 26.1 and 31.1 degrees 2-theta±0.2 degrees 2-theta;
b) a solid state 13 C NMR spectrum having peaks at 45.0, 112.8, 140.0, 146.9, 157.2 and 161.3 ppm±0.2 ppm; or
c) a solid state 13 C NMR spectrum having the following chemical shift absolute differences from a reference peak at 41.7 ppm±2 ppm of 3.3, 71.1, 98.3, 105.2, 115.5 and 119.6 ppm±0.1 ppm and
d) combinations of (a) with (b), (a) with (c), or (b) with (c).
2 . Crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 , which is characterized by an XRPD pattern having peaks at 14.4, 19.0, 19.7, 26.1 and 31.1 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, or four additional peaks selected from 10.4, 17.2, 21.6 and 29.4 degrees two theta±0.2 degrees 2-theta.
3 . Crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 , which is characterized by an XRPD pattern having peaks at: 10.4, 14.4, 17.2, 19.0, 19.7, 21.6, 26.1, 29.4 and 31.1 degrees 2-theta #0.2 degrees 2-theta.
4 . Crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 , which is characterized by: an XRPD pattern substantially as depicted in FIG. 2 , and/or a solid state 13 C NMR spectrum substantially as depicted in any of FIG. 5 a , 5 b or 5 c.
5 . Crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 , wherein said crystalline form is hydrate form, optionally wherein the crystalline form contains about 5.0% to about 6.0% (w/w) of water.
6 . Crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 , which contains no more than about 20% of any other crystalline forms of Ensifentrine ethane-1,2-disulfonate.
7 . Crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 , which contains no more than about 20% of amorphous Ensifentrine ethane-1,2-disulfonate.
8 . A pharmaceutical composition comprising a crystalline form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 .
9 . A pharmaceutical formulation comprising a crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 , or a with at least one pharmaceutically acceptable excipient.
10 . A process for preparing a pharmaceutical formulation comprising combining a crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 , with at least one pharmaceutically acceptable excipient.
11 . A method of treating chronic obstructive pulmonary disease, cystic fibrosis or asthma, comprising administering a therapeutically effective amount of a crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate according to claim 1 to a subject in need of the treatment.
12 . A medicament for treating chronic obstructive pulmonary disease (COPD), cystic fibrosis and asthma, comprising the crystalline Form ES2 of Ensifentrine ethane-1,2-disulfonate, according to claim 1 .