Advantageous morphic form of AT-527 hemi-sulfate salt
Advantageous isolated morphic Form III of the hemi-sulfate salt of AT-527 that exhibits a faster rate of dissolution over the amorphous form leading to increased bioavailability and thus efficacy for therapeutic administration in a solid dosage form to treat viral indications, as well as processes for its manufacture.
1 . A Compound A Form III isolated crystalline morphic form, wherein Compound A is of structure:
and the morphic form is characterized by an XRPD pattern comprising at least three 2theta values selected from 5.2±0.2°, 7.3±0.2°, 8.9±0.2°, 10.4±0.2° 13.6±0.2°, 14.7±0.2°, 17.0±0.2°, 18.2±0.2°, 19.9±0.2°, and 21.8±0.2°.
2 . The Compound A Form III of claim 1 , characterized by an XRPD pattern comprising at least four 2theta values selected from 5.2±0.2°, 7.3±0.2°, 8.9±0.2°, 10.4±0.2° 13.6±0.2°, 14.7±0.2°, 17.0±0.2°, 18.2±0.2°, 19.9±0.2°, and 21.8±0.2°.
3 . The Compound A Form III of claim 1 , characterized by an XRPD pattern comprising at least five 2theta values selected from 5.2±0.2°, 7.3±0.2°, 8.9±0.2°, 10.4±0.2° 13.6±0.2°, 14.7±0.2°, 17.0±0.2°, 18.2±0.2°, 19.9±0.2°, and 21.8±0.2°.
4 . The Compound A Form III of claim 1 , characterized by an XRPD pattern comprising at least six 2theta values selected from 5.2±0.2°, 7.3±0.2°, 8.9±0.2°, 10.4±0.2° 13.6±0.2°, 14.7±0.2°, 17.0±0.2°, 18.2±0.2°, 19.9±0.2°, and 21.8±0.2°.
5 . The Compound A Form III of claim 1 , characterized by an XRPD pattern comprising the following 2theta values: 5.2±0.2°, 7.3±0.2°, 8.9±0.2°, 13.6±0.2°, 17.0±0.2°, 19.9±0.2°, and 21.8±0.2°.
6 . A pharmaceutical composition comprising Compound A Form III of claim 1 and a pharmaceutically acceptable carrier.
7 . The pharmaceutical composition of claim 6 , in a solid dosage form.
8 . The pharmaceutical composition of claim 7 , wherein the solid dosage form is a tablet.
9 . The pharmaceutical composition of claim 7 , wherein the solid dosage form is a capsule.
10 . The pharmaceutical composition of claim 7 that comprises at least about 400 mg of Compound A Form III.
11 . The pharmaceutical composition of claim 7 that comprises at least about 200 mg of Compound A Form III.
12 . The pharmaceutical composition of claim 7 that comprises at least about 250 mg of Compound A Form III.
13 . The pharmaceutical composition of claim 7 that comprises at least about 300 mg of Compound A Form III.
14 . The pharmaceutical composition of claim 7 that comprises at least about 350 mg of Compound A Form III.
15 . The pharmaceutical composition of claim 7 that comprises about 300 mg of Compound A Form III.
16 . The pharmaceutical composition of claim 7 that comprises between about 600 mg and about 1,200 mg of Compound A Form III.
17 . The pharmaceutical composition of claim 7 that comprises between about 400 mg and about 1,000 mg of Compound A Form III.
18 . The pharmaceutical composition of claim 7 that comprises between about 500 mg and about 800 mg of Compound A Form III.
19 . The pharmaceutical composition of claim 7 that comprises from about 300 mg to about 1,200 mg of Compound A Form III.
20 . The pharmaceutical composition of claim 7 that comprises about 600 mg of Compound A Form III.
21 . The pharmaceutical composition of claim 7 that comprises at least 300 mg of Compound A Form III.
22 . The pharmaceutical composition of claim 7 that comprises 300 mg of Compound A Form III.
23 . The pharmaceutical composition of claim 7 that comprises from 300 mg to 1,200 mg of Compound A Form III.