Solid dispersions and pharmaceutical compositions comprising a substituted indane and methods for the preparation and use thereof
Provided herein are solid dispersions comprising a HIF-2α inhibitor, pharmaceutical compositions comprising the solid dispersions, and methods for treating HIF-2α-mediated diseases and conditions.
1. A pharmaceutical solid dosage form for oral delivery of a compound of Formula (I),
wherein the solid dosage form comprises
a solid dispersion comprising the compound of Formula (I), a pharmaceutically acceptable polymer selected from the group consisting of Hypromellose acetate succinate (HPMCAS), cellulose acetate phthalate (CAP), and polyethylene glycol vinyl acetate vinylcaprolactam,
one or more pharmaceutically acceptable excipients comprising a binder, a filler, a disintegrant and a lubricant,
wherein the binder is a microcrystalline cellulose, and
the solid dosage form is a capsule or a tablet.
2. The solid dosage form of claim 1 , wherein the solid dosage form is a tablet.
3. The solid dosage form of claim 1 , wherein the one or more pharmaceutically acceptable excipients further comprise a glidant.
4. The solid dosage form of claim 1 , wherein the solid dispersion is present in an amount from 15% to 50% by weight of the solid dosage form.
5. The solid dosage form of claim 1 , wherein the pharmaceutically acceptable polymer is HPMCAS.
6. The solid dosage form of claim 1 , wherein the pharmaceutically acceptable polymer is present in an amount from 15% to 35% by weight of the solid dosage form.
7. The solid dosage form of claim 1 , wherein the compound of Formula (I) is present in an amount from 1% to 15% by weight of the solid dosage form.
8. The solid dosage form of claim 1 , comprising 5 mg to 100 mg of the compound of Formula (I).
9. The solid dosage form of claim 1 , comprising about 10 mg of the compound of Formula (I).
10. The solid dosage form of claim 1 , comprising about 40 mg of the compound of Formula (I).
11. The pharmaceutical solid dosage form of claim 1 , wherein the one or more excipients further comprise mannitol, croscarmellose sodium and magnesium stearate.
12. The pharmaceutical solid dosage form of claim 1 , wherein the pharmaceutical solid dosage form comprises, by weight of the solid dosage form:
(a) 15% to 50% of a solid dispersion comprising the compound of Formula (I) and HMPCAS;
(b) 20% to 50% of the microcrystalline cellulose;
(c) 20% to 40% of a mannitol;
(d) 1.0% to 5.0% of a croscarmellose sodium; and
(e) 0.25% to 1.25% of magnesium stearate.