Solid Forms of Upadacitinib
Provided are solid forms of upadacitinib. Specific solid forms include an amorphous solid dispersion of upadacitinib and magnesium chloride and crystalline forms of upadacitinib incorporating magnesium chloride, magnesium acetate, magnesium orotate, magnesium fumarate, magnesium citrate, or orotic acid. Also provided are pharmaceutical compositions including the upadacitinib solid forms and the use of these forms in the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, and/or ankylosing spondylitis.
1 . A crystalline form of upadacitinib comprising upadacitinib and a magnesium salt.
2 . The crystalline form of claim 1 , wherein the magnesium salt is selected form the group consisting of magnesium chloride, magnesium acetate, magnesium orotate, magnesium fumarate, and magnesium citrate.
3 . The crystalline form of claim 2 , wherein the molar ratio of upadacitinib to the magnesium salt is from about 1:0.4 to about 1:5.
4 . The crystalline form of claim 3 , wherein the crystalline form is a hydrate.
5 . The crystalline form of claim 3 , wherein the crystalline form is anhydrous.
6 . A crystalline form of upadacitinib comprising upadacitinib and magnesium chloride.
7 . The crystalline form of claim 6 , wherein the molar ratio of upadacitinib to the magnesium chloride is about 1:0.4 to about 1:1.
8 . The crystalline form of claim 7 , wherein the crystalline form is a hydrate.
9 . The crystalline form of upadacitinib of claim 7 , characterized by a PXRD diffractogram comprising peaks, expressed in degrees 2θ (±0.2°), at 4.3°, 5.5°, and 21.1°.
10 . The crystalline form of claim 9 , further comprising at least three peaks, expressed in degrees 2θ (±0.2°), selected from the group consisting of: 8.1°, 8.7°, 13.3°, 15.7°, 17.1°, and 23.6°.
11 . The crystalline form of claim 9 , further comprising peaks, expressed in degrees 2θ (±0.2°), at 8.1°, 8.7°, 13.3°, 15.7°, 17.1°, and 23.6°.
12 . The crystalline form of claim 7 , providing a PXRD diffractogram comprising peaks in substantially the same positions (±0.2°2θ) as those shown in FIG. 1 .
13 . The crystalline form of claim 7 , providing a PXRD diffractogram comprising peaks in substantially the same positions (±0.2°2θ) as those shown in FIG. 9 .
14 . An amorphous solid dispersion of upadacitinib comprising upadacitinib and a magnesium salt.
15 . The amorphous solid dispersion of claim 14 , wherein the molar ratio of upadacitinib to the magnesium salt is from about 1:0.4 to about 1:1.
16 . The amorphous solid dispersion of claim 15 , wherein the molar ratio of upadacitinib to the magnesium salt is from about 1:0.4 to about 1:0.6.
17 . The amorphous solid dispersion of claim 15 , wherein the magnesium salt is magnesium chloride.
18 . A pharmaceutical composition comprising the crystalline form of upadacitinib of claim 6 and one or more pharmaceutically acceptable excipients.
19 . The pharmaceutical composition of claim 18 , wherein the composition is in the form of a capsule or a tablet.
20 . The pharmaceutical composition of claim 19 , wherein the composition is in the form of an extended-release tablet.
21 . A pharmaceutical composition comprising the amorphous solid dispersion of claim 14 and one or more pharmaceutically acceptable excipients.