Polymorphs of 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S dioxide and methods of making and using the same
View Patent ↗Disclosed herein are novel polymorphs of 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide. Also described herein are novel pharmaceutical compositions comprising one or more 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide polymorphs, methods of making, and related methods of treatment.
1. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I, wherein said Form I exhibits a powder X-ray diffractogram comprising a peak at about 5.89 degrees 2-theta.
2. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I, wherein said Form I exhibits a powder X-ray diffractogram comprising a peak at about 7.82 degrees 2-theta.
3. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I of claim 2 , wherein said Form I exhibits a powder X-ray diffractogram further comprising peaks at about 8.93 degrees 2-theta.
4. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I of claim 1 , wherein said Form I exhibits a powder X-ray diffractogram further comprising peaks at about 7.82, and about 8.93 degrees 2-theta.
5. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I, wherein said Form I exhibits a powder X-ray diffractogram comprising peaks at about 12.66, about 13.32, about 16.26, and about 17.64 degrees 2-theta.
6. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I of claim 4 , wherein said Form I exhibits a powder X-ray diffractogram further comprising peaks at about 12.66, about 13.32, and about 17.64 degrees 2-theta.
7. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I, wherein said Form I exhibits a powder X-ray diffractogram comprising peaks at about 5.89, about 7.82, about 8.93, about 12.66, about 13.32, about 14.72, about 16.26, about 17.64, about 19.50, about 21.56, about 22.58, and about 25.19 degrees 2-theta.
8. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I, wherein said Form I exhibits a DSC thermogram comprising an endothermic transition at about 139 degrees C.
9. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II, wherein said Form II exhibits a powder X-ray diffractogram comprising a peak at about 8.52 degrees 2-theta.
10. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II, wherein said Form II exhibits a powder X-ray diffractogram comprising a peak at about 10.46 degrees 2-theta.
11. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II of claim 9 , wherein said Form II exhibits a powder X-ray diffractogram further comprising peaks at about 10.46 degrees 2-theta.
12. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II, wherein said Form II exhibits a powder X-ray diffractogram comprising peaks at about 15.05, about 17.14, and about 20.99 degrees 2-theta.
13. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II of claim 11 , wherein said Form II exhibits a powder X-ray diffractogram further comprising peaks at about 15.05, and about 17.14 degrees 2-theta.
14. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II of claim 13 , wherein said Form II exhibits a powder X-ray diffractogram further comprising peaks at about 20.99, and about 21.66 degrees 2-theta.
15. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II, wherein said Form II exhibits a powder X-ray diffractogram comprising peaks at about 8.52, about 10.46, about 15.05, about 17.14, about 18.22, about 20.99, about 21.66, about 22.68, about 23.35, about 23.88, about 24.55, and about 26.71 degrees 2-theta.
16. 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II, wherein said Form II exhibits a DSC thermogram comprising an endothermic transition at about 148 degrees C.
17. A method of making a polymorph of 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide of claim 7 , comprising:
(a) providing 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide sodium salt; and
(b) contacting said 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide sodium salt with an appropriate acid so as to desalify said sodium salt;
(c) contacting the desalified mixture from step (b) with an appropriate solvent; and
(d) crystallizing said polymorph of 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide.
18. A method of making a polymorph of 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide of claim 15 , comprising:
(a) providing 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I;
(b) contacting said 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I with an appropriate solvent; and
(c) crystallizing said polymorph of 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide.
19. A method of treating a mammal suffering from depression, irritable bowel syndrome, attention deficit hyperactivity disorder, or asthma, comprising administering to said mammal an effective amount of the 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form I of claim 4 .
20. A method of treating a mammal suffering from depression, irritable bowel syndrome, attention deficit hyperactivity disorder, or asthma, comprising administering to said mammal an effective amount of the 7-[(3-chloro-6,11-dihydro-6-methyldibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide Form II of claim 15 .