Multi-use torasemide composition
An aqueous composition including torasemide and at least one organic solvent, to a bottle or container including the composition, and to a kit including the bottle or container and a device for delivery of the composition (for example a syringe). A use of at least one organic solvent for increasing the stability and/or the antimicrobial properties of a composition including torasemide. A method for preparing the composition.
1. An aqueous composition comprising:
torasemide;
a buffer or an alkalizing agent; and
an organic solvent that is an alcohol derived from propane, wherein a concentration of the organic solvent by weight is greater than or equal to 30% relative to a total weight of the aqueous composition, wherein the aqueous composition is physically, chemically, and antimicrobially stable for at least 24 months when stored at a temperature between 25 and 30° C.
2. The aqueous composition according to claim 1 , wherein a concentration of the torasemide by weight is between 0.01% and 5% relative to the total weight of the composition.
3. The aqueous composition according to claim 1 , wherein the buffer or alkalizing agent is selected from the group consisting of tromethamine (TRIS), triethanolamine, diethanolamine, monoethanolamine, sodium hydroxide, potassium hydroxide, ammonium hydroxide and meglumine, wherein a concentration of the buffer or of the alkalizing agent by weight is between 1 and 5% relative to the total weight of the aqueous composition.
4. The aqueous composition according to claim 1 , further comprising a rheology modifier, selected from the group consisting of synthetic hydrophilic polymers of acrylic acid, polysaccharides, gums, polyvinyl povidone, poloxamers, hydrophilic silica and poly(meth)acrylates, wherein a concentration of rheology modifier by weight is between 0.01 and 10% relative to the total weight of the aqueous composition.
5. The aqueous composition according to claim 1 , further comprising a sweetener.
6. The aqueous composition according to claim 1 , wherein a viscosity of the aqueous composition is between 0.001 and 5 Pa·s.
7. The aqueous composition according to claim 1 , further comprising a pharmaceutically acceptable excipient.
8. The aqueous composition according to claim 1 , wherein a pH of the aqueous composition is between 7.5 and 10.
9. A method of treatment, comprising:
determining the existence of clinical signs associated with congestive heart failure, treatment of kidney diseases and hypertension are present in a subject; and
applying a composition to the subject based on the determining, wherein the composition comprises:
torasemide;
a buffer or an alkalizing agent; and
an organic solvent that is an alcohol derived from propane, wherein a concentration of the organic solvent by weight is greater than or equal to 30% relative to a total weight of the composition, wherein only the torasemide is an active ingredient of the composition that treats the congestive heart failure, treatment of kidney diseases and/or hypertension present in the subject.
10. A method of manufacturing a composition, the method comprising:
providing an aqueous composition comprising torasemide; and
applying an organic solvent to the aqueous composition, wherein the organic solvent is an alcohol derived from propane, at a concentration by weight greater than or equal to 30%, wherein a composition defined by the aqueous composition and the organic solvent applied to the aqueous composition is physically, chemically, and antimicrobially stable for at least 24 months when stored at a temperature between 25 and 30° C.
11. A method for preparing a composition, comprising:
(a) adding a buffer or an alkalizing agent to water at room temperature and stirring to obtain mixture 1 ,
(b) adding torasemide to mixture 1 and stirring to obtain mixture 2 ,
(c) gradually adding a rheology modifier, with stirring, to obtain mixture 3 ,
(d) stirring until a clear solution is obtained, to obtain mixture 4 ,
(e) adding an organic solvent that is an alcohol derived from propane, wherein a concentration of the organic solvent by weight is greater than or equal to 30% relative to a total weight of the composition and stirring until a clear solution is obtained, to obtain mixture 5 , wherein mixture 5 is physically, chemically, and antimicrobially stable for at least 24 months when stored at a temperature between 25 and 30° C.
12. A containment system comprising:
a container; and
a composition comprising:
torasemide;
a buffer or an alkalizing agent; and
an organic solvent that is an alcohol derived from propane, wherein a concentration of the organic solvent by weight is greater than or equal to 30% relative to a total weight of the composition, wherein the composition is physically, chemically, and antimicrobially stable for at least 24 months when stored at a temperature between 25 and 30° C.;
wherein the composition is present within the container.
13. A kit-comprising:
a containment system comprising:
a container; and
a composition comprising:
torasemide;
a buffer or an alkalizing agent; and
an organic solvent that is an alcohol derived from propane, wherein a concentration of the organic solvent by weight is greater than or equal to 30% relative to a total weight of the composition, wherein the composition is physically, chemically, and antimicrobially stable for at least 24 months when stored at a temperature between 25 and 30° C.;
wherein the composition is present within the container; and
a system for administering the composition.
14. The aqueous composition according to claim 1 , wherein the alcohol is selected from the group consisting of propylene glycol, glycerol, propane-1,3-diol, propanol, isopropanol and mixtures thereof.
15. The method of treatment according to claim 9 , wherein the alcohol is selected from the group consisting of propylene glycol, glycerol, propane-1,3-diol, propanol, isopropanol and mixtures thereof.
16. The method of treatment according to claim 9 , wherein the subject is a human.
17. The method of treatment according to claim 9 , wherein the subject is an animal.
18. The method according to claim 10 , wherein the organic solvent endows the aqueous composition with antimicrobial properties.
19. The method according to claim 10 , wherein the alcohol is selected from the group consisting of propylene glycol, glycerol, propane-1,3-diol, propanol, isopropanol and mixtures thereof.
20. The method according to claim 11 , wherein the alcohol is selected from the group consisting of propylene glycol, glycerol, propane-1,3-diol, propanol, isopropanol and mixtures thereof.
21. The method according to claim 11 , wherein the method is performed under an inert atmosphere.
22. The method according to claim 11 , wherein process (d) comprises adding a pharmaceutically acceptable excipient.
23. The method according to claim 11 , further comprising adjusting the volume, with stirring.
24. The method according to claim 11 , further comprising adjusting the pH.
25. The containment system according to claim 12 , wherein the alcohol is selected from the group consisting of propylene glycol, glycerol, propane-1,3-diol, propanol, isopropanol and mixtures thereof.
26. The containment system according to claim 12 , wherein the container is a bottle.
27. The kit according to claim 13 , wherein the alcohol is selected from the group consisting of propylene glycol, glycerol, propane-1,3-diol, propanol, isopropanol and mixtures thereof.
28. The kit according to claim 13 , wherein the container is a bottle.
29. The aqueous composition according to claim 1 , wherein only the torasemide is an active ingredient of that composition that treats congestive heart failure, treatment of kidney diseases and/or hypertension present in a subject.
30. The method of treatment according to claim 9 , wherein the composition is physically, chemically, and antimicrobially stable for at least 24 months when stored at a temperature between 25 and 30° C.
31. The method of treatment according to claim 30 , wherein a pH of the composition is between 7.5 and 10.
32. The method of manufacture according to claim 10 , wherein only the torasemide is an active ingredient of that composition that treats congestive heart failure, treatment of kidney diseases and/or hypertension present in a subject.
33. The method of manufacture according to claim 10 , wherein a pH of the composition is between 7.5 and 10.
34. The method of preparing a composition according to claim 11 , wherein only the torasemide is an active ingredient of mixture 5 that treats congestive heart failure, treatment of kidney diseases and/or hypertension present in a subject.
35. The method of preparing a composition according to claim 11 , wherein a pH of mixture 5 is between 7.5 and 10.
36. The containment system according to claim 12 , wherein only the torasemide is an active ingredient of that composition that treats congestive heart failure, treatment of kidney diseases and/or hypertension present in a subject.
37. The containment system according to claim 12 , wherein a pH of the composition is between 7.5 and 10.
38. The kit according to claim 13 , wherein only the torasemide is an active ingredient of that composition that treats congestive heart failure, treatment of kidney diseases and/or hypertension present in a subject.
39. The kit according to claim 13 , wherein a pH of the composition is between 7.5 and 10.