US2012076857A1PendingUtilityA1
Forms of rifaximin and uses thereof
Individually held — no corporate assignee on recordPriority: Feb 25, 2008Filed: Sep 6, 2011Published: Mar 29, 2012
Est. expiryFeb 25, 2028(~1.6 yrs left)· nominal 20-yr term from priority
Inventors:Karen S. GushurstDonglai YangMelanie RoeNathan Carl SchultheissPetinka VlahovaJeffrey S. StultsTravis L. Houston
A61P 31/00A61P 29/00A61P 31/04A61P 1/04C07D 471/22C07D 498/18C07D 498/22A61K 31/437C07D 498/16A61P 1/18A61P 1/12A61P 1/00Y02A50/30
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Claims
Abstract
The present invention relates to Rifaximin polymorphic, salt, hydrate, and amorphous forms, to their use in medicinal preparations and to therapeutic methods using them.
Claims
exact text as granted — not AI-modified1 . Polymorphic Form ξ, Form γ−1 (ξ), Form η, Form α-dry, Form ι, Form mesylate or amorphous forms of rifaximin.
2 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 4.7 (doublet), 7.6 (doublet), and 9.5 degrees 2-θ;
3 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 4.7 (doublet), 7.3, and 8.2 degrees 2-θ.
4 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 7.6 (doublet), 8.6, and 10.5 degrees 2-θ.
5 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 8.2, 8.6, and 9.5 degrees 2-θ.
6 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 10.2 (triplet), 12.6 (quintet), and 13.2 (doublet) degrees 2-θ; or 7.3, 10.5, and 12.9 (doublet) degrees 2-θ.
7 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 7.3, 7.6 (doublet), 8.2, 8.6 degrees 2-θ; or 4.7 (doublet), 7.3, 7.6 (doublet), 9.5, and 10.5 degrees 2-θ.
8 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 8.2, 8.6, 9.5, 10.2 (triplet), and 10.5 degrees 2-θ.
9 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 8.6, 9.5, 10.2 (triplet), 10.5, and 11.2 (doublet) degrees 2-θ.
10 . The polymorph Form ξ of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 4.7 (doublet), 6.3, 6.4, 7.3, 7.6 (doublet), 8.2, 8.6, 9.5, 10.2 (triplet), 10.5, 11.2 (doublet), 11.9 (doublet), 12.2 (weak), 12.6 (quintet), 12.9 (doublet), 13.2 (doublet) degrees 2-θ.
11 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.1, 7.3, and 7.5 degrees 2-θ.
12 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.1, 7.3, and 7.9 degrees 2-θ.
13 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.1, 7.3, and 8.8 degrees 2-θ.
14 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.1, 7.3, and 12.7 degrees 2-θ.
15 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.1, 7.5, and 8.8 degrees 2-θ.
16 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.1, 7.5, and 7.9 degrees 2-θ.
17 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, and 7.3 degrees 2-θ.
18 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, and 7.9 degrees 2-θ.
19 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, and 12.7 degrees 2-θ.
20 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, and 7.5 degrees 2-θ.
21 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, and 8.8 degrees 2-θ.
22 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.1, 7.3, 7.5, 7.9, 8.8, and 12.7 degrees 2-θ.
23 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, 7.3, 7.5, 7.9, 8.8, 12.7 degrees 2-θ.
24 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, 7.3, 7.9, 8.8, and 12.7 degrees 2-θ.
25 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, 7.3, 7.5, 8.8, and 12.7 degrees 2-θ.
26 . The polymorph Form η of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.3, 6.1, 7.3, 7.5, 7.9, 8.8, and 12.7 degrees 2-θ.
27 . The polymorph Form ι of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.9±0.1; 9.0±0.1; or 12.7±0.1; 13.9±0.1; 14.9±0.1; or 5.9±0.1; 7.9±0.1; 12.7±0.1; or 5.9±0.1; 9.0±0.1; 12.7±0.1; or 5.9±0.1; 13.9±0.1; 14.9±0.1; or 5.9±0.1; 7.9±0.1; 14.9±0.1; or 9.0±0.1; 12.7±0.1; 14.9±0.1; or 5.9±0.1; 7.9±0.1; 9.0±0.1; 14.9±0.1; or 5.9±0.1; 7.9±0.1; 9.0±0.1; 12.7±0.1; or 5.9±0.1; 7.9±0.1; 9.0±0.1; 12.7±0.1; 13.9±0.1; 14.9±0.1.
28 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.4±0.1; 7.9±0.1; 9.4±0.1.
29 . The polymorph Form ι of claim 1 , wherein polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 7.4±0.1; 20.0±0.1; 20.9±0.1.
30 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 13.9±0.1; 14.9±0.1.
31 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 20.0±0.1; 20.9±0.1; 23.4±0.1.
32 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 13.9±0.1; 14.9±0.1; 20.0±0.1; 20.9±0.1.
33 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 7.4±0.1; 12.7±0.1; 13.9±0.1; 23.4±0.1.
34 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.4±0.1; 7.9±0.1; 12.7±0.1; 13.9±0.1; 14.9±0.1; 20.0±0.1; 20.9±0.1; 23.4±0.1.
35 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.4±0.1; 7.9±0.1; 9.0±0.1; 9.4±0.1; 12.7±0.1; 13.9±0.1; 14.9±0.1; 20.0±0.1; 20.9±0.1; 23.4±0.1
36 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 13.9±0.1; 14.9±0.1; 20.0±0.1; 20.9±0.1; or 5.9±0.1; 13.9±0.1; 14.9±0.1; or 7.4±0.1; 12.7±0.1; 13.9±0.1; 23.4±0.1; or 20.0±0.1; 20.9±0.1; 23.4±0.1; or 5.9±0.1; 7.4±0.1; 7.9±0.1; 12.7±0.1; 13.9±0.1; 14.9±0.1; 20.0±0.1; 20.9±0.1; 23.4±0.1; or 5.9±0.1; 7.4±0.1; 7.9±0.1; 9.4±0.1; or 7.4±0.1; 20.0±0.1; 20.9±0.1; or 5.9±0.1; 7.4±0.1; 7.9±0.1; 9.0±0.1; 9.4±0.1; 12.7±0.1; 13.9±0.1; 14.9±0.1; 20.0±0.1; 20.9±0.1; 23.4±0.1.
37 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.9±0.1; 9.0±0.1; 12.7±0.1; 13.9±0.1; 14.9±0.1.
38 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.9±0.1; 9.0±0.1.
39 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 12.7±0.1; 13.9±0.1; 14.9±0.1.
40 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.9±0.1; 12.7±0.1.
41 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 9.0±0.1; 12.7±0.1.
42 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 13.9±0.1; 14.9±0.1.
43 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.9±0.1; 14.9±0.1.
44 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 9.0±0.1; 12.7±0.1; 14.9±0.1.
45 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.9±0.1; 9.0±0.1; 14.9±0.1.
46 . The polymorph Form ι of claim 1 , wherein the polymorph Form ι exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.9±0.1; 7.9±0.1; 9.0±0.1; 12.7±0.1.
47 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 8.46±0.10; 10.95±0.10; or 5.34±0.10; 6.93±0.10; 8.46±0.10; or 5.34±0.10; 10.95±0.10; 16.23±0.10; 17.70±0.10; or 7.41±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; or 16.23±0.10; 17.70±0.10; 17.94±0.10; 19.29±0.10; 22.77±0.10; or 16.23±0.10; 17.70±0.10; 19.29±0.10; 22.77±0.10; or 5.34±0.10; 16.23±0.10; 17.70±0.10; or 5.34±0.10; 6.93±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; 16.23±0.10; 17.70±0.10; 17.94±0.10; 19.29±0.10; 22.77±0.10.
48 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 6.93±0.10; 7.41±0.10; or 5.34±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10; or 5.34±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; 16.23±0.10; or 6.93±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; or 10.62±0.10; 10.95±0.10; 16.23±0.10; 17.70±0.10; 17.94±0.10; or 6.93±0.10; 7.41±0.10; 8.46±0.10; or 5.34±0.10; 6.93±0.10; 7.41±0.10; 17.94±0.10; or 5.34±0.10; 6.93±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10; or 5.34±0.10; 6.93±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; 16.23±0.10; or 5.34±0.10; 6.93±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; 16.23±0.10; 17.70±0.10; 17.94±0.10; 22.77±0.10; 24.81±0.10; 27.81±0.10.
49 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 6.93±0.10; 7.41±0.10.
50 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/− 0.20 degree θ) at 5.34±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10.
51 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/− 0.20 degree θ) at 5.34±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; 16.23±0.10.
52 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.93±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10.
53 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 10.62±0.10; 10.95±0.10; 16.23±0.10; 17.70±0.10; 17.94±0.10; 0.29±0.10.
54 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 6.93±0.10; 7.41±0.10; 8.46±0.10.
55 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 6.93±0.10; 7.41±0.10; 17.94±0.10.
56 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 6.93±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10.
57 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 6.93±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; 16.23±0.10.
58 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 6.93±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; 16.23±0.10; 17.70±0.10; 17.94±0.10; 0.29±0.10; 22.77±0.10; 24.81±0.10; 27.81±0.10.
59 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 8.46±0.10; 10.95±0.10.
60 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 6.93±0.10; 8.46±0.10.
61 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 10.95±0.10; 16.23±0.10; 17.70±0.10.
62 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 7.41±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10.
63 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 16.23±0.10; 17.70±0.10; 17.94±0.10; 19.29±0.10; 22.77±0.10.
64 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 16.23±0.10; 17.70±0.10; 19.29±0.10; 22.77±0.10.
65 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 16.23±0.10; 17.70±0.10.
66 . The mesylate Form of claim 1 , wherein the mesylate Form of rifaximin exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.34±0.10; 6.93±0.10; 7.41±0.10; 8.46±0.10; 10.62±0.10; 10.95±0.10; 16.23±0.10; 17.70±0.10; 17.94±0.10; 19.29±0.10; 22.77±0.10.
67 . The polymorph amorphous forms of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 7.3 (approximate halo maximum), 11.3-17.8 (amorphous halo range), and 15.8 (approximate halo maximum) degrees 2-θ.
68 . The polymorph amorphous forms of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.1-10.1 (amorphous halo range), 11.3-17.8 (amorphous halo range), and 15.8 (approximate halo maximum) degrees 2-θ.
69 . The polymorph amorphous forms of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.1-10.1 (amorphous halo range), 7.3 (approximate halo maximum), and 11.3-17.8 (amorphous halo range) degrees 2-θ.
70 . The polymorph amorphous forms of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.1-10.1 (amorphous halo range), 7.3 (approximate halo maximum), and 15.8 (approximate halo maximum) degrees 2-θ.
71 . The polymorph amorphous forms of claim 1 , wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) at 5.1-10.1 (amorphous halo range), 7.3 (approximate halo maximum), 11.3-17.8 (amorphous halo range), 15.8 (approximate halo maximum) degrees 2-θ.
72 . The polymorph amorphous forms of claim 1 , wherein the polymorph exhibits Thermogravimetric analyses (TGA) of a 1.5% weight loss at 100° C.
73 . The polymorph amorphous forms of claim 1 , wherein the polymorph exhibits Differential Scanning Calorimetry (DSC) of a broad endotherm at about 78° C. and a minor endotherm at 203° C.
74 . The polymorph amorphous forms of claim 1 , wherein the polymorph exhibits Modulated Differential Scanning Calorimetry (MDSC) having a glass transition (Tg) temperature onset to be about 199° C.
75 . The Form ξ, Form η, Form α-dry, Form ι or amorphous forms of rifaximin of claim 1 , wherein the polymorph contains less than 5% by weight total impurities.
76 . The Form ξ, Form γ−1 (ξ), Form η, Form α-dry, Form ι, Form mesylate or amorphous forms of rifaximin of claim 1 , wherein the form is at least 50% pure, or at least 75% pure, or at least 80% pure, or at least 90% pure, or at least 95% pure, or at least 98% pure.
77 . A pharmaceutical composition comprising one or more of a Form ξ, Form γ−1 (ξ), Form η, Form α-dry, Form ι, Form mesylate or amorphous forms of rifaximin and a pharmaceutically acceptable carrier.
78 . The pharmaceutical composition of claim 77 , further comprising one or more pharmaceutically acceptable excipients.
79 . The pharmaceutical composition of claim 78 , wherein the excipient comprises one or more of a diluting agent, binding agent, lubricating agent, disintegrating agent, coloring agent, flavoring agent or sweetening agent.
80 . The pharmaceutical composition of claim 77 , formulated as coated or uncoated tablets, hard or soft gelatin capsules, sugar-coated pills, lozenges, wafer sheets, pellets or powders in sealed packets.
81 . The pharmaceutical composition of claim 77 , formulated for topical use.
82 . A method of treating, preventing or alleviating a bowel related disorder comprising administering to a subject in need thereof an effective amount of one or more of Form ξ, Form γ-1 (ξ), Form η, Form α-dry, Form ι, mesylate Form or amorphous forms of rifaximin.
83 . The method according to claim 82 , wherein the subject is suffering from at least one bowel related disorder selected from the group consisting of irritable bowel syndrome, travelers' diarrhea, small intestinal bacterial overgrowth, Crohn's disease, chronic pancreatitis, pancreatic insufficiency, enteritis and colitis.
84 . A process for producing Form ξ of rifaximin comprising forming an EtOH slurry of an initial Form α-dry of rifaximin at ambient temperature and crystallizing rifaximin from the slurry.
85 . The method of claim 84 , further comprising crash cooling the slurry prior to crystallization.
86 . The process for producing Form ξ of rifaximin of claim 84 , wherein the EtOH slurry comprises an EtOH/H 2 O slurry in the ratio of from between 1 to 0.02-0.45.
87 . A process for producing a mixture of polymorphs ξ and γ of rifaximin comprising humidifying Form ξ of rifaximin.
88 . A process for the production of Form β of rifaximin comprising crystallizing amorphous rifaximin by vapor diffusion in methanol and tetrahydrofuran, using water as an antisolvent.
89 . A process for producing Form η of rifaximin comprising drying Form ξ of rifaximin.
90 . A process for producing amorphous rifaximin comprising grinding Form γ of rifaximin or a mixture of Form γ and Form η of rifaximin.
91 . A process for producing amorphous rifaximin comprising crash precipitation of rifaximin from ethyl acetate with heptane.
92 . The process of claim 91 , further comprising milling the produced amorphous rifaximin.
93 . A process for producing amorphous rifaximin comprising lyophilization of rifaximin in p-dioxane:water 1:1, and fast evaporation from acetone.
94 . The process of claim 93 , further comprising milling the produced amorphous rifaximin.
95 . A process for producing amorphous rifaximin comprising precipitation of rifaximin from acetone.
96 . The process of claim 95 , further comprising milling the produced amorphous rifaximin.
97 . A process of producing β-2 Form of rifaximin comprising precipitating an α-dry Form of rifaximin in a mixture of EtOH and water.
98 . A process of producing ξ and ξ and γ mixtures of rifaximin comprising precipitating the initial forms of rifaximin in the manner set forth in Table 15.
99 . A process of producing a mesylate Form of rifaximin comprising the conditions set forth in Table 26.
100 . A process of producing mixtures of Form γ of rifaximin, Form γ and Form η mixtures, and Form γ and Form ξ mixtures comprising precipitating the initial forms in the manner set forth in Table 14.
101 . A process of producing mixtures of Form γ−1 (ξ) and Form γ−1 (ξ) and Form β mixtures of rifaximin, comprising precipitating the initial forms in the manner set forth in Table 13.
102 . A process for producing Form ι of rifaximin comprising performing the conditions set forth in Table 27.
103 . A process for producing α, β, α and β mixtures comprising precipitating the initial forms of rifaximin in the manner set forth in Tables 10 and 11.
104 . A process for producing ε-dry comprising precipitating the initial forms of rifaximin in the manner set forth in Table 16.
105 . A process for producing η and η and γ mixtures of rifaximin comprising precipitating the initial forms in the manner set forth in Table 17.
106 . A process for producing amorphous rifaximin comprising precipitating the initial forms of rifaximin in the manner set forth in Table 18.
107 . A process for producing Form ξ, Form β-1, mixtures of Form α and Form β, Form β-2, and Form ξ-1 of rifaximin comprising precipitating the initial forms of rifaximin in the manner set forth in Table 19.
108 . A process for producing Form α-dry, Form α, Form ε-dry, Form η, Form ε-dry, Form ξ, Form γ, amorphous Form, From γ−1 (ξ) and From β mixtures, Form ξ and Form γ mixtures and Form γ and From η mixtures of rifaximin comprising precipitating the initial forms of rifaximin in the manner set forth in Tables 20-22.
109 . A kit for treating a bowel disorder in a subject, comprising one or more of a Form ξ, Form η, or an amorphous form of rifaximin and instructions for use.
110 . A packaged composition comprising, a therapeutically effective amount of one or more of a Form ξ, Form η, Form α-dry, Form ι or amorphous forms of rifaximin and a pharmaceutically acceptable carrier or diluent, wherein the composition is formulated for treating a subject suffering from or susceptible to a bowel disorder, and packaged with instructions to treat a subject suffering from or susceptible to a bowel disorder.
111 . A mesylate form of rifaximin.
112 . Polymorphic Form β-1, Form β-2, Form γ−1(ξ) or Form ε-dry of rifaximin.
113 . The Form γ−1 (ξ) of claim 1 , comprising an XRPD pattern substantially similar to FIG. 1 .
114 . The Form ξ of rifaximin of claim 1 , comprising an XRPD pattern substantially similar to FIG. 2 .
115 . The Form η of rifaximin of claim 1 , comprising an XRPD pattern substantially similar to FIG. 3 .
116 . The Form amorphous of rifaximin of claim 1 , comprising an XRPD pattern substantially similar to FIG. 4 .
117 . The Form amorphous of rifaximin of claim 1 , comprising a TGA and a DSC substantially similar to FIG. 5 .
118 . The Form ξ of rifaximin of claim 1 , comprising an XRPD pattern substantially similar to FIG. 8 .
119 . The Form η of rifaximin of claim 1 , comprising an XRPD pattern substantially similar to FIG. 9 .
120 . The Form amorphous of rifaximin of claim 1 , comprising an XRPD pattern substantially similar to FIG. 10 .
121 . The Form ι of rifaximin of claim 1 , comprising an XRPD pattern substantially similar to FIG. 11 .
122 . The mesylate Form of rifaximin of claim 93 comprising an XRPD pattern substantially similar to FIG. 15 .
123 . The Form amorphous of rifaximin of claim 1 , comprising a DSC substantially similar to FIG. 20 .
124 . The Form amorphous of rifaximin of claim 1 , comprising a cycling DSC substantially similar to FIG. 21 .
125 . The Form amorphous of rifaximin of claim 1 , comprising a TG substantially similar to FIG. 22 .
126 . The Form amorphous of rifaximin of claim 1 , comprising a cycling DSC substantially similar to FIG. 24 .
127 . The Form amorphous of rifaximin of claim 1 , comprising a TG substantially similar to FIG. 25 .
128 . The Form amorphous of rifaximin of claim 1 , comprising a cycling DSC substantially similar to FIG. 27 .
129 . The Form amorphous of rifaximin of claim 1 , comprising a TG substantially similar to FIG. 28 .
130 . The Form amorphous of rifaximin of claim 1 , comprising a modulated DSC substantially similar to FIG. 29 .
131 . The Form amorphous of rifaximin of claim 1 , comprising a modulated DSC substantially similar to FIG. 30 .
132 . The Form ι of claim 1 , comprising thermal data substantially similar to FIG. 31 .
133 . The Form ι of claim 1 , comprising proton NMR spectrum substantially similar to FIG. 34 .
134 . The Form α □dry of claim 1 , comprising a TGA and DSC substantially similar to FIG. 37 .
135 . The Form β-1 of rifaximin of claim 94 , comprising the XRPD substantially similar FIG. 38 .
136 . The Form β-2 of rifaximin of claim 94 , comprising the XRPD substantially similar FIG. 38 .
137 . The Form β-2 of rifaximin of claim 94 , comprising aTGA and/or DSC substantially similar to FIG. 39 .
138 . The Form ε-dry of claim 94 , comprising a TGA and/or a DSC substantially similar to FIG. 40 .
139 . The Form ε-dry of claim 94 , comprising an XRPD pattern substantially similar to FIG. 41 .Join the waitlist — get patent alerts
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