PHARMACEUTICAL COMPOSITION

Abstract

A pharmaceutical composition is described. The composition comprises: (i) a drug component comprising at least one antiviral compound that is suitable for treating viruses that cause adverse effects in the lungs; and (ii) a propellant. The composition can be delivered to the lungs using a metered dose inhaler (MDI).

Claims

1. A pharmaceutical composition comprising: (i) a drug component comprising at least one antiviral compound that is suitable for treating viruses that cause adverse effects in the lungs; and (ii) a propellant.

2. (canceled)

3. The pharmaceutical composition of claim 1, wherein the at least one antiviral compound is a prodrug of an adenosine nucleoside analogue.

4. The pharmaceutical composition of claim 1, wherein the at least one antiviral compound includes remdesivir.

5. (canceled)

6. The pharmaceutical composition of claim 1, wherein the drug component additionally comprises at least one further respiratory drug selected from the corticosteroids, the long acting beta-2 agonists (LABA), the long acting muscarinic antagonists and the short acting muscarinic antagonists.

7. The pharmaceutical composition of claim 1, wherein the propellant component comprises at least one hydrofluoroalkane.

8. The pharmaceutical composition of claim 7, wherein the at least one hydrofluoroalkane is selected from the group consisting 1,1,1,2-tetrafluoroethane (HFA-134a), 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea), 1,1-difluoroethane (HFA-152a) and mixtures thereof.

9-10. (canceled)

11. The pharmaceutical composition of claim 1, further comprising a polar excipient.

12. The pharmaceutical composition of claim 11, wherein the polar excipient is selected from the group consisting of water, ethanol, glycerol and their mixtures.

13. (canceled)

14. The pharmaceutical composition of claim 1, further comprising an acid stabiliser.

15. The pharmaceutical composition of claim 1 in the form of a suspension.

16. The pharmaceutical composition of claim 15 further comprising a co-suspension agent.

17. The pharmaceutical composition of claim 11 in the form of a solution.

18. The pharmaceutical composition of claim 17 further comprising an additive to increase the solubility of the antiviral compound in the mixture of the propellant and polar excipient.

19. The pharmaceutical composition of claim 1, further comprising a surfactant component comprising at least one surfactant compound.

20. A pharmaceutical solution for delivery using a metered dose inhaler (MDI) comprising: (i) a drug component comprising remdesivir; (ii) a propellant comprising at least one hydrofluoroalkane selected from the group consisting of 1,1,1,2-tetrafluoroethane (HFA-134a), 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea), 1,1-difluoroethane (HFA-152a) and mixtures thereof; and (iii) a polar excipient comprising ethanol, water or an ethanol/water mixture.

21. (canceled)

22. The pharmaceutical solution of claim 20, further comprising (iv) a surfactant component comprising at least one surfactant compound selected from oleic acid and lecithin.

23. A pharmaceutical suspension for delivery using a MDI comprising: (i) a drug component comprising remdesivir; and (ii) a propellant comprising at least one hydrofluoroalkane selected from the group consisting of 1,1,1,2-tetrafluoroethane (HFA-134a), 1,1,1,2,3,3,3-heptafluoropropane (HFA-227ea), 1,1-difluoroethane (HFA-152a) and mixtures thereof.

24. The pharmaceutical suspension of claim 23 further comprising (iii) ethanol.

25. (canceled)

26. The pharmaceutical suspension of claim 23, further comprising (iv) a surfactant component comprising at least one surfactant compound selected from polyvinylpyrrolidone, oleic acid and lecithin.

27-35. (canceled)

36. A sealed and pressurized aerosol container for use with a metered dose inhaler (MDI) that contains a pharmaceutical composition of claim 1.

37. A metered dose inhaler (MDI) fitted with a sealed and pressurized aerosol container of claim 36.

38. A method for treating a patient suffering from a viral infection that causes adverse effects in the lungs, said method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition of claim 1.

39. The method of claim 38, wherein the pharmaceutical composition is delivered to the patient using a metered dose inhaler (MDI).

40. The method of claim 38, wherein the viral infection that causes adverse effects in the lungs is Covid-19.

41-42. (canceled)

Description

EXAMPLE 1

[0111] MDIs containing solution formulations of remdesivir may be prepared in a mixing vessel by adding a weighed amount of remdesivir and adding the requisite quantity of water. If desired, beta-cyclodextrin is also added at this stage. The mixture is stirred until the remdesivir has dissolved. If desired, HCl(aq) is added to bring the pH of the resulting solution to between pH3 and pH4. The aqueous solution is then mixed with ethanol and the resulting solution having a remdesivir concentration of at least 5 mg/mL is transferred in aliquots to an open MDI can (H&T Presspart 19 mL can size) and crimped closed with the valve (Aptar DF30). The propellant (HFA-134a, HFA-152a) is pressure filled into the can. Suitable final compositions in the can are recorded in Table 1 below.

TABLE-US-00001 TABLE 1 1A 1B 1C 1D Remdesivir(mg) 100 50 100 50 Water(g) 1 1 0.5 0.5 Ethanol(g) 2 1 3 2 Propellant q.s. q.s. q.s. q.s.

EXAMPLE 2

[0112] MDIs containing solution formulations of remdesivir may be prepared in a mixing vessel by adding a weighed amount of remdesivir and adding the requisite quantity of ethanol. The mixture is stirred until the remdesivir has dissolved. The solution is transferred in aliquots to an open MDI can (H&T Presspart 19 mL can size) and crimped closed with the valve (Aptar DF30). The propellant (HFA-134a, HFA-152a) is pressure filled into the can. Suitable final compositions in the can are recorded in Table 2 below.

TABLE-US-00002 TABLE 2 2A 2B 2C 2D Remdesivir(mg) 100 50 100 50 Ethanol(g) 2 1 4 2 Propellant q.s. q.s. q.s. q.s.

EXAMPLE 3

[0113] MDIs containing suspension formulations of remdesivir may be prepared in a mixing vessel capable of containing the propellant by adding a weighed amount of remdesivir and if desired, the requisite quantity of ethanol and either PVP or oleic acid surfactant. The propellant is added and the mixture stirred before it is pressure-transferred in aliquots to a pre-crimped MDI can (H&T Presspart 19 mL can size) with the Aptar DF30 valve. Suitable final compositions in the can are recorded in Table 3 below.

TABLE-US-00003 TABLE 3 3A 3B 3C 3D Remdesivir(mg) 100 50 100 50 Ethanol(g) 0 0 0.1 0.1 PVP(mg) 0.01 0 0 0.01 Oleic acid(mg) 0 0.01 0.01 0 Propellant q.s. q.s. q.s. q.s.