ST-246 (tecovirimat monohydrate) suspension formulations
The present invention is directed to a dry suspension for reconstitution containing Tecovirimat (ST-246) powder and simethicone. The dry suspension is dispersed in water to provide an aqueous pharmaceutical suspension formulation for oral administration for treating orthopoxvirus infections and/or eczema vaccinatum. The suspension formulation exhibits excellent stability and good dissolution and has an improved taste and texture.
1. A dry suspension comprising 4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocycloprop[f]isoindol-2-(1H)-yl)-benzamide (Tecovirimat (ST-246)) and simethicone.
2. A dry suspension according to claim 1 further comprising at least one suspending agent.
3. A dry suspension according to claim 2 wherein the suspending agent is methylcellulose.
4. A dry suspension according to claim 2 wherein the suspending agent is hydroxypropyl cellulose.
5. A dry suspension according to claim 1 further comprising a lubricant.
6. A dry suspension according to claim 5 wherein the lubricant is magnesium stearate.
7. A dry suspension according to claim 1 further comprising an excipient.
8. A dry suspension according to claim 7 wherein the excipient is lactose monohydrate.
9. A dry suspension according to claim 1 wherein the ST-246 is selected from a group consisting of ST-246 polymorph Form I, ST-246 polymorph Form II, ST-246 polymorph Form III, ST-246 polymorph Form IV, ST-246 polymorph Form V and ST-246 polymorph Form VI.
10. A dry suspension according to claim 1 wherein the ST-246 is micronized.
11. A dry suspension according to claim 1 wherein the ST-246 is granulated.
12. A dry suspension according to claim 1 wherein the simethicone is granular form.
13. A dry suspension according to claim 1 wherein the simethicone is in liquid form and adsorbed on lactose monohydrate.
14. A dry suspension according to claim 1 comprising 0.2 to 6.0 wt % simethicone.
15. A dry suspension according to claim 3 comprising 1 to 5 wt % methylcellulose.
16. A dry suspension according to claim 4 comprising 1.0 to 30 wt % hydroxypropylcellulose.
17. A dry suspension according to claim 1 wherein the particle size of ST-246 is 0.5 to 10 μm.
18. An aqueous pharmaceutical suspension formulation comprising a dry suspension according to claim 1 and water.
19. A formulation according to claim 18 further comprising a pharmaceutically acceptable ingredient.
20. A formulation according to claim 19 wherein the pharmaceutically acceptable ingredient is selected from the group consisting of carrier, excipient, diluent, additive, filler, lubricant and binder.
21. A method of treating orthopoxvirus infections and/or eczema vaccinatum comprising oral administration to a subject in need thereof a formulation according to claim 18 .
22. The method of claim 21 , wherein the subject is administered 400 mg to 2000 mg daily of ST-246.
23. A process of making the dry suspension according to claim 1 , comprising mixing ST-246 with simethicone and optionally at least one suspending agent, at least one lubricant, at least one excipient, at least one further anti-foaming agent, at least one sweetener and/or at least one flavoring.