Sustained-release dosage forms of ruxolitinib
The present invention relates to sustained-release formulations and dosage forms of ruxolitinib, or a pharmaceutically acceptable salt thereof, which are useful in the treatment of Janus kinase-associated diseases such as myeloproliferative disorders.
1. A sustained-release dosage form comprising:
(1) about 12.2 wt % ruxolitinib phosphate;
(2) about 20 to about 22 wt % hypromellose;
(3) about 22 to about 42.3 wt % microcrystalline cellulose;
(4) about 20 to about 42.3 wt % lactose monohydrate;
(5) about 1 wt % colloidal silicon dioxide;
(6) about 0.5 wt % magnesium stearate; and
(7) about 2 wt % stearic acid;
wherein administration of said dosage form to a human for at least 16 weeks results in a mean decrease in mean hemoglobin of no more than about 15 g/L or a mean decrease in mean base platelet count of no more than about 100×10 9 /L.
2. The sustained-release dosage form of claim 1 , wherein the ruxolitinib phosphate is present in an amount of about 25 mg on a free base basis.
3. The sustained-release dosage form of claim 1 , which is a tablet.
4. The sustained-release dosage form of claim 1 , which comprises:
(1) about 12.2 wt % ruxolitinib phosphate;
(2) about 20 wt % hypromellose;
(3) about 22 wt % microcrystalline cellulose;
(4) about 42.3 wt % lactose monohydrate;
(5) about 1 wt % colloidal silicon dioxide;
(6) about 0.5 wt % magnesium stearate; and
(7) about 2 wt % stearic acid.
5. The sustained release dosage form of claim 4 , wherein the ruxolitinib phosphate is present in an amount of about 25 mg on a free base basis.
6. The sustained-release dosage form of claim 4 , which is a tablet.
7. The sustained-release dosage form of claim 1 , which comprises:
(1) about 12.2 wt % ruxolitinib phosphate;
(2) about 22 wt % hypromellose;
(3) about 42.3 wt % microcrystalline cellulose;
(4) about 20 wt % lactose monohydrate;
(5) about 1 wt % colloidal silicon dioxide;
(6) about 0.5 wt % magnesium stearate; and
(7) about 2 wt % stearic acid.
8. The sustained-release dosage form of claim 7 , wherein the ruxolitinib phosphate is present in an amount of about 25 mg on a free base basis.
9. The sustained-release dosage form of claim 7 , which is a tablet.
10. The sustained-release dosage form of claim 1 , which is an oral sustained-release dosage form.
11. The sustained-release dosage form of claim 4 , which is an oral sustained-release dosage form.
12. The sustained-release dosage form of claim 7 , which is an oral sustained-release dosage form.