Methods and compositions for treating edema refractory to oral diuretics

1. A stable pharmaceutical composition comprising (i) an aqueous solution having a pH of between about 5 and about 9, (ii) between about 4 mg/mL and about 20 mg/mL potassium bumetanide salt, and (iii) one or more pharmaceutically acceptable excipients, wherein the aqueous solution is free of a buffering agent other than the buffer formed by bumetanide free acid combined with potassium hydroxide, wherein the pharmaceutical composition is formulated for intranasal administration and wherein the pharmaceutical composition resides in a metered spray pump device.

2. A pharmaceutical composition of claim 1 comprising (i) an aqueous solution having between about 5 mg/mL and about 10 mg/mL potassium bumetanide salt, (ii) one or more pharmaceutically acceptable excipients, and (iii) wherein the aqueous solution has a pH of between about 6 and about 8.

3. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable excipients comprise a surfactant or a permeation enhancer.

4. The pharmaceutical composition of claim 1 , wherein the aqueous solution has a pH of between about 6 and about 8.

5. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises low viscosity sodium carboxymethyl cellulose, or a pharmaceutically acceptable salt thereof.

6. The pharmaceutical composition of claim 1 , wherein the one or more pharmaceutically acceptable excipients comprises a preservative, a viscosity enhancer, or a tonicity agent.

7. A stable pharmaceutical composition comprising (i) an aqueous solution having a pH of between about 5 and about 9, (ii) between about 4 mg/mL and about 20 mg/mL potassium bumetanide salt, and (iii) one or more pharmaceutically acceptable excipients, wherein the aqueous solution is free of a buffering agent other than the buffer formed by bumetanide free acid combined with potassium hydroxide, wherein the pharmaceutical composition is formulated for sublingual administration and wherein the pharmaceutical composition resides in a metered spray pump device.

8. A pharmaceutical composition of claim 7 comprising (i) an aqueous solution having between about 5 mg/mL and about 10 mg/mL potassium bumetanide salt, (ii) one or more pharmaceutically acceptable excipients, and (iii) wherein the aqueous solution has a pH of between about 6 and about 8.

9. The pharmaceutical composition of claim 7 , wherein the pharmaceutically acceptable excipients comprise a surfactant or a permeation enhancer.

10. The pharmaceutical composition of claim 7 , wherein the aqueous solution has a pH of between about 6 and about 8.

11. The pharmaceutical composition of claim 7 , wherein the one or more pharmaceutically acceptable excipients comprises low viscosity sodium carboxymethyl cellulose, or a pharmaceutically acceptable, salt thereof.

12. The pharmaceutical composition of claim 7 , wherein the one or more pharmaceutically acceptable excipients comprises a preservative, a viscosity enhancer, or a tonicity agent.