ORAL SOLID DOSE FORMULATIONS
Disclosed are novel pharmaceutical compositions comprising gepotidacin, such as gepotidacin mesylate dihydrate, gepotidacin mesylate anhydrate or gepotidacin anhydrate. The present disclosure also provides methods for making the pharmaceutical composition comprising gepotidacin, and methods of treating bacterial infections using such pharmaceutical composition.
1 . A pharmaceutical composition comprising gepotidacin and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition comprises about 45% to 75% by weight of gepotidacin (measured as free base).
2 . The pharmaceutical composition according to claim 1 , wherein the gepotidacin is in a crystalline form.
3 . The pharmaceutical composition according to claim 2 , wherein the crystalline form is gepotidacin mesylate dihydrate, gepotidacin mesylate anhydrate or gepotidacin anhydrate.
4 . The pharmaceutical composition according to claim 3 , wherein the crystalline form is gepotidacin mesylate dihydrate.
5 . The pharmaceutical composition according to claim 4 , wherein the gepotidacin mesylate dihydrate is characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three or at least four diffraction angles, when measured using Cu K α radiation, selected from the group consisting of about 9.0, 11.5, 13.4, 14.3, 14.9, 15.5, 17.6, 18.6, and 20.7 degrees 2θ.
6 . The pharmaceutical composition according to claim 4 , wherein the gepotidacin mesylate dihydrate is characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with FIG. 1 .
7 . The pharmaceutical composition according to claim 4 , wherein the pharmaceutical composition comprises about 60% to 90% by weight of gepotidacin mesylate dihydrate.
8 . The pharmaceutical composition according to claim 4 , wherein the pharmaceutical composition comprises about 60% to 80% by weight of gepotidacin mesylate dihydrate, and wherein the one or more excipients comprise a diluent, a disintegrant, and a glidant.
9 . The pharmaceutical composition according to claim 8 , comprising:
about 65% to 75% by weight of gepotidacin mesylate dihydrate,
about 20% to 25% by weight of the diluent,
about 4% to 10% by weight of the disintegrant, and
about 0.5% to 2% by weight of the glidant.
10 . The pharmaceutical composition according to claim 8 , wherein
the diluent is selected from the group consisting of microcrystalline cellulose, lactose, sucrose, dextrose, mannitol, sorbitol, starch, cellulose, calcium sulfate, dibasic calcium phosphate, and a combination thereof:
the disintegrant is selected from the group consisting of crospovidone, sodium starch glycolate, croscarmellose, croscarmellose sodium, alginic acid, sodium alginate, sodium carboxymethyl cellulose, and a combination thereof; and
the glidant is selected from the group consisting of colloidal silicon dioxide, magnesium stearate, and a combination thereof.
11 . The pharmaceutical composition according to claim 7 , wherein the one or more excipients further comprise a lubricant.
12 . The pharmaceutical composition according to claim 11 , wherein the lubricant is selected from the group consisting of stearic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, talc, and a combination thereof.
13 . The pharmaceutical composition according to claim 11 , wherein the lubricant comprises about 0.5% to 5% by weight.
14 . The pharmaceutical composition according to claim 3 , wherein the crystalline form is gepotidacin anhydrate.
15 . The pharmaceutical composition according to claim 14 , wherein the gepotidacin anhydrate is characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three or at least four diffraction angles, when measured using Cu K α radiation, selected from the group consisting of about 8.8, 10.8, 11.7, 12.8, 13.2, 14.4, 16.3, 19.9, 20.8, and 25.0 degrees 2θ.
16 . The pharmaceutical composition according to claim 14 , wherein the gepotidacin anhydrate is characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with FIG. 4 .
17 . The pharmaceutical composition according to claim 1 , which is in the form of a tablet.
18 . A method of treating a bacterial infection in a human in need thereof comprising administering to the human the pharmaceutical composition according to claim 1 .
19 . The method according to claim 18 , wherein the bacterial infection is uncomplicated urinary tract infection or an infection by Neisseria gonorrhoeae.
20 . The method according to claim 18 , wherein the bacterial infection is uncomplicated urinary tract infection, and the pharmaceutical composition is administered at a dose of 1500 mg of gepotidacin (measured as free base) twice daily for 5 days.
21 . The method according to claim 18 , wherein the bacterial infection is infection by Neisseria gonorrhoeae , and the pharmaceutical composition is administered at a dose of 3000 mg of gepotidacin (measured as free base), followed by a second dose of 3000 mg after 10-12 hours.
22 - 23 . (canceled)