Quinine sulfate/bisulfate solid complex; methods of making; and methods of use thereof

1. Quinine sulfate acetic acid solid complex comprising one or more of the following:

XRPD peak positions at 8.4, 15.2, 16.6, 17.0, 17.8, 19.3, 20.4, 23.8, 25.2, and 25.7±0.1 degree 2-theta;

XRPD peak positions as in Table 4;

an X-ray powder diffraction pattern as in FIG. 1 ;

FT-Raman peaks at 1364, 1429, 1445, and 2954±4 cm −1 ;

FT-Raman peaks substantially as in Table 5; or

FT-Raman spectrum as in FIG. 2 .

2. The solid complex of claim 1 , wherein the solid complex is quinine sulfate acetic acid co-crystal monohydrate.

3. Quinine bisulfate tartaric acid solid complex comprising one or more of the following:

XRPD peak positions at 9.4, 10.4, 13.8, 15.2, 15.6, 16.8, 17.4, 18.7, 19.5, and 20.5±0.1 degrees 2-theta;

XRPD peak positions as in Table 9;

an X-ray powder diffraction pattern as in FIG. 3 ;

FT-Raman peaks at 767, 1386, 1431, and 1622±4 cm −1 ;

FT-Raman peaks as in Table 10; or

FT-Raman spectrum as in FIG. 4 .

4. A composition, comprising:

the quinine sulfate acetic acid solid complex of claim 3 or the quinine bisulfate tartaric acid solid complex of claim 3 ; and

a pharmaceutically acceptable excipient.

5. The composition of claim 4 , wherein the composition is a solid oral dosage formulation.

6. A method of treating a patient in need of quinine therapy, comprising:

administering to a patient in need thereof the solid complex of claim 1 or claim 3 .

7. A method of treating a patient in need of quinine therapy, comprising:

administering to a patient in need thereof the composition of claim 4 .

8. The method of claim 6 , wherein the solid complex is used to treat malaria caused by Plasmodium species, uncomplicated Plasmodium falciparum malaria, severe or complicated Plasmodium falciparum malaria, malaria caused by Plasmodium vivax , leg muscle cramps, or babesiosis; or for the prophylaxis of malaria or leg muscle cramps.

9. The method of claim 7 , wherein the composition is used to treat malaria caused by Plasmodium species, uncomplicated Plasmodium falciparum malaria, severe or complicated Plasmodium falciparum malaria, malaria caused by Plasmodium vivax , leg muscle cramps, or babesiosis; or for the prophylaxis of malaria or leg muscle cramps.

10. A method of preparing the solid complex of claim 1 , comprising one of the following:

i.) milling a combination of quinine sulfate and acetic acid to form quinine sulfate acetic acid solid complex;

ii) preparing quinine sulfate acetic acid solid complex by liquid diffusion in ethyl acetate; or

iii) adding an anti-solvent to a solution containing quinine sulfate, a guest, and optionally a solvent system; and precipitating a quinine sulfate solid complex, wherein the guest is acetic acid.

11. A method of preparing the solid complex of claim 3 , comprising one of the following:

i) crystallizing a solid complex from a solution containing quinine sulfate, a guest, and optionally a solvent system with optionally evaporating the solvent system from the solution, wherein the guest is DL-tartaric acid; or

ii) dissolving quinine sulfate and tartaric acid in a lower alkyl alcohol with heating, and allowing the solid complex to precipitate.

12. The method of claim 11 , wherein i) further comprises seeding the solution.

13. The method of claim 10 , wherein the anti-solvent of iii) is acetone.

14. The method of claim 10 , wherein iii) further comprises slurrying the quinine sulfate, guest, and solvent system.

15. The solid complex of claim 1 comprising XRPD peak positions at 8.4, 15.2, 16.6, 17.0, 17.8, 19.3, 20.4, 23.8, 25.2, and 25.7±0.1 degree 2-theta.

16. The solid complex of claim 1 comprising an X-ray powder diffraction pattern as in FIG. 1 .

17. The solid complex of claim 3 comprising XRPD peak positions at 9.4, 10.4, 13.8, 15.2, 15.6, 16.8, 17.4, 18.7, 19.5, and 20.5±0.1 degrees 2-theta.

18. The solid complex of claim 3 comprising an X-ray powder diffraction pattern as in FIG. 3 .