Solid state forms of pemafibrate

Abstract

The present disclosure relates to solid state forms of Pemafibrate processes for preparation thereof and pharmaceutical compositions thereof.

1 . A crystalline form of Pemafibrate selected from:
 (A) crystalline Form A, which is characterized by data selected from one or more of the following:
 i. an XRPD pattern having peaks at 7.7, 8.2, 11.1, 11.6 and 18.6 degrees 2-theta±0.2 degrees 2-theta; 
 ii. an XRPD pattern as depicted in  FIG. 1 ; 
 iii. a solid state  13 C-NMR spectrum with peaks at 171.2, 158.0, 147.9, 141.1 and 137.7 ppm±0.2 ppm; 
 iv. a solid state  13 C-NMR spectrum having the following chemical shift absolute differences from a peak at 127.8 ppm±1 ppm: 43.4, 30.2, 20.1, 13.3 and 9.9 ppm±0.1 ppm; 
 v. a solid state  13 C-NMR spectrum substantially as depicted in  FIG. 7 a   ; or combinations of (i)-(v); 
   (B) crystalline Form C, which is characterized by data selected from one or more of the following:
 i. an XRPD pattern having peaks at 5.1, 13.8, 14.7, 16.9 and 17.2 degrees 2-theta±0.2 degrees 2-theta; 
 ii. an XRPD pattern as depicted in  FIG. 3 ; 
 iii. a solid state  13 C-NMR spectrum with peaks at 153.8, 147.9, 139.5, 129.7 and 125.0 ppm±0.2 ppm; 
 iv. a solid state  13 C-NMR spectrum having the following chemical shift absolute differences from a peak at 107.3 ppm±1 ppm: 46.5, 40.6, 32.1, 22.4 and 17.6 ppm±0.1 ppm; 
 v. a solid state  13 C-NMR spectrum substantially as depicted in  FIG. 9 a   ; or combinations of (i)-(v); 
 or 
   (C) crystalline Form D which is characterized by data selected from one or more of the following:
 i. an XRPD pattern having peaks at 12.4, 14.2, 16.2, 22.2 and 23.0 degrees 2-theta±0.2 degrees 2-theta; 
 ii. an XRPD pattern as depicted in  FIG. 4 ; 
 iii. a solid state  13 C-NMR spectrum with peaks at 153.3, 146.9, 129.8, 124.0 and 111.8 ppm±0.2 ppm; 
 iv. a solid state  13 C-NMR spectrum having the following chemical shift absolute differences from a peak at 107.5 ppm±1 ppm: 45.8, 39.4, 22.3, 16.5 and 4.3 ppm±0.1 ppm; 
 v. a solid state  13 C-NMR spectrum substantially as depicted in  FIG. 10 a   ; or combinations of (i)-(v). 
   
     
     
         2 . The crystalline Form A of Pemafibrate according to  claim 1 , which is characterized by data selected from one or more of the following:
 i. an XRPD pattern having peaks at 7.7, 8.2, 11.1, 11.6 and 18.6 degrees 2-theta±0.2 degrees 2-theta;   ii. an XRPD pattern as depicted in  FIG. 1 ;   iii. a solid state  13 C-NMR spectrum with peaks at 171.2, 158.0, 147.9, 141.1 and 137.7 ppm±0.2 ppm;   iv. a solid state  13 C-NMR spectrum having the following chemical shift absolute differences from a peak at 127.8 ppm±1 ppm: 43.4, 30.2, 20.1, 13.3 and 9.9 ppm±0.1 ppm;   v. a solid state  13 C-NMR spectrum substantially as depicted in  FIG. 7 a   ; or combinations of (i)-(v).   
     
     
         3 . The crystalline Form A of Pemafibrate according to  claim 2 , which is characterized by an XRPD pattern having peaks at 7.7, 8.2, 11.1, 11.6 and 18.6 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 9.8, 14.1, 16.4, 17.4 and 20.1 degrees 2-theta±0.2 degrees 2-theta. 
     
     
         4 . The crystalline Form C of Pemafibrate according to  claim 1 , which is characterized by data selected from one or more of the following:
 i. an XRPD pattern having peaks at 5.1, 13.8, 14.7, 16.9 and 17.2 degrees 2-theta±0.2 degrees 2-theta;   ii. an XRPD pattern as depicted in  FIG. 3 ;   iii. a solid state  13 C-NMR spectrum with peaks at 153.8, 147.9, 139.5, 129.7 and 125.0 ppm±0.2 ppm;   iv. a solid state  13 C-NMR spectrum having the following chemical shift absolute differences from a peak at 107.3 ppm±1 ppm: 46.5, 40.6, 32.1, 22.4 and 17.6 ppm±0.1 ppm;   v. a solid state  13 C-NMR spectrum substantially as depicted in  FIG. 9 a   ; or combinations of (i)-(v).   
     
     
         5 . The crystalline Form C of Pemafibrate according to  claim 4 , which is characterized by an XRPD pattern having peaks at 5.1, 13.8, 14.7, 16.9 and 17.2 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 8.6, 10.2, 18.3, 19.7 and 21.5 degrees 2-theta±0.2 degrees 2-theta. 
     
     
         6 . The crystalline Form D of Pemafibrate according to  claim 1 , which is characterized by data selected from one or more of the following:
 i. an XRPD pattern having peaks at 12.4, 14.2, 16.2, 22.2 and 23.0 degrees 2-theta±0.2 degrees 2-theta;   ii. an XRPD pattern as depicted in  FIG. 4 ;   iii. a solid state  13 C-NMR spectrum with peaks at 153.3, 146.9, 129.8, 124.0 and 111.8 ppm±0.2 ppm;   iv. a solid state  13 C-NMR spectrum having the following chemical shift absolute differences from a peak at 107.5 ppm±1 ppm: 45.8, 39.4, 22.3, 16.5 and 4.3 ppm±0.1 ppm;   v. a solid state  13 C-NMR spectrum substantially as depicted in  FIG. 10 a   ; or combinations of (i)-(v).   
     
     
         7 . The crystalline Form D of Pemafibrate according to  claim 6 , which is characterized by an XRPD pattern having peaks at 12.4, 14.2, 16.2, 22.2 and 23.0 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 3.9, 7.9, 8.8, 18.4 and 21.2 degrees 2-theta±0.2 degrees 2-theta. 
     
     
         8 . A pharmaceutical composition comprising the crystalline Form A of Pemafibrate according to  claim 2 , and at least one pharmaceutically acceptable excipient. 
     
     
         9 . A pharmaceutical formulation comprising the crystalline Form C of Pemafibrate according to  claim 4 , and at least one pharmaceutically acceptable excipient. 
     
     
         10 . A pharmaceutical formulation comprising the crystalline Form D of Pemafibrate according to  claim 6 , and at least one pharmaceutically acceptable excipient.