Claims
- 1. A method of making a prepackaged, stable, premeasured, premixed aqueous nebulizer solution for reducing medication error and enhancing therapeutic compliance of an individual suffering from chronic obstructive pulmonary disease; said method comprising the steps:
(a) adding water, albuterol and ipratropium bromide into a container at a temperature between about 2° C. and about 50° C. to form a solution; wherein the final concentration of the albuterol and ipratropium bromide in the nebulizer solution ranges from about 0.06 wt. % to about 0.1 wt. % albuterol and about 0.03 wt. % to about 0.1 wt. % ipratropium; (b) adjusting the pH of said solution to about 3.0 to about 5.0; (c) adding sufficient osmotic adjusting agent to the solution so that the isotonicity of said solution is from about 280 mOsm/kg to about 320 mOsm/kg; and (d) filling the solution into at least one single dispensing vial, said vial being filled with about 0.1 ml to about 3 ml of the solution such that the solution in each vial comprises a unit dose of a therapeutically effective amount of albuterol and ipratropium bromide, wherein the dosage of albuterol is about 2.5 mg and the dosage of ipratropium bromide is about 0.5 mg; (e) enclosing the one or more dispensing vials containing the solution; and (f) wherein the stability of the solution in the dispensing containers is such that the solution is therapeutically effective following storage for 12 months at 25° C.; wherein the solution is suitable for nebulization in a nebulizer.
- 2. The method of claim 1, wherein the step of filling the one or more dispensing vials comprises filling the vials with 3 ml of the solution into the one or more vials, and wherein the step of adding water, albuterol and ipratropium into the container comprises adding the water, albuterol and ipratropium at a temperature between 18° C. and 25° C.
- 3. The method of claim 1 wherein the step of filling the one or more dispensing vials comprises filling the vials with about 0.1 ml to about 2 ml of the solution into the one or more vials.
- 4. The method of claim 1, wherein the step of filling the one or more dispensing vials comprises filling the vials with about 2.84 ml to about 3.30 ml of the solution into the one or more vials.
- 5. The method of claim 1, wherein the step of adjusting the pH of the solution comprises adding hydrochloric acid.
- 6. The method of claim 1, wherein the step of adding an osmotic agent to adjust the isotonicity of the solution comprises adding an osmotic adjusting agent selected from the group consisting of sodium chloride, potassium chloride, zinc chloride, calcium chloride and mixtures thereof.
- 7. The method of claim 1, further comprising the step of sterilizing the solution by passing it through at least one filter or by steam sterilization.
- 8. The process of claim 1, wherein the step of adjusting the pH of the solution comprises adding hydrochloric acid to adjust the pH of the solution to about 3.5.
- 9. The method of claim 1, wherein the step of enclosing the one or more vials comprises sterile sealing the one or more vials after the solution is filled therein.
- 10. The method of claim 1, wherein the step of filling the solution into the one or more vials comprises filling the solution into a low density polyethylene dispensing vial.
- 11. The method of claim 1, wherein the step of adding albuterol comprises adding albuterol in the form of an acid addition salt thereof.
- 12. The method of claim 1, wherein the step of adding albuterol comprises adding albuterol in the form of albuterol sulfate.
- 13. The method of claim 1, wherein the step of adding the osmotic agent comprises adding sodium chloride.
- 14. The method of claim 1, wherein the step of adding the osmotic adjusting agent comprises adding an agent selected from the group consisting of mannitol, glycerol, dextrose and mixtures thereof.
- 15. The method of claim 1, wherein the step of adding the osmotic adjusting agent comprises adding sufficient osmotic agent so that the solution filled in the one or more dispensing vials comprises about 0.4 wt. % to about 1.0 wt. % ionic salt.
- 16. The method of claim 1, wherein the step of adding the osmotic adjusting agent comprises adding sufficient osmotic agent so that the solution filled in the one or more dispensing vials comprises about 0.9% by weight of an osmotic adjusting agent.
- 17. The method of claim 1, further comprising the step of packaging the one or more dispensing vials in an aluminum foil pouch.
- 18. The method of claim 7, wherein the step of sterilizing the solution comprises passing the solution through 0.2 micron sterilizing cartridge filter.
- 19. The method of claim 7, further comprising the step of passing the solution through a second sterilizing filter.
- 20. The method of claim 19, wherein the second sterilizing filter is a 0.2 micron sterilizing cartridge.
- 21. The method of claim 1, wherein the step of adding albuterol and ipratropium comprises adding sufficient albuterol and ipratropium so that the concentration of albuterol is about 0.083 wt. % and the concentration of ipratropium bromide is about 0.017 wt. % in the solution.
- 22. The method of claim 1, wherein the step of filling the one or more vials with the solution comprises filling the one or more vials with the solution free of benzalkonium chloride and wherein the step of enclosing the one or more vials comprises enclosing the one or more vials containing the solution free of benzalkonium chloride.
- 23. The method of claim 1, further comprising the step of adding benzalkonium chloride to the inhalation solution.
- 24. A method of making a prepackaged, stable, premeasured, premixed aqueous nebulizer solution for reducing medication error and enhancing therapeutic compliance of an individual suffering from chronic obstructive pulmonary disease; said method comprising the steps:
(a) adding water into a container at a temperature of between about 2° C. and about 50° C.; (b) adding at least a therapeutically effective amount of albuterol and ipratropium bromide to the container until dissolved; (c) adding water to adjust the final volume to a desired amount, thus forming a solution; (d) wherein the final concentration of the albuterol and ipratropium bromide in the solution ranges from about 0.06 wt. % to about 0.1 wt. % albuterol and about 0.03 wt. % to about 0.1 wt. % ipratropium; (e) adding sufficient acid to the solution so that the pH of the solution is from about 3.0 to about 4.0; (f) adding sufficient osmotic adjusting agent to the solution so that the isotonicity of the solution is about 280 mOsm/kg to about 320 mOsm/kg; (g) passing the solution through a form-fill-seal (FFS) machine; (h) passing the solution through a filling nozzle into one or more preformed low density polyethylene dispensing vials; (i) filling each of the one or more dispensing vials with about 0.1 ml to about 3 ml of the solution such that each container contains a sterile, unit dose of albuterol and ipratropium bromide, said dose ranging from about 2.00 mg to about 3.00 mg albuterol and 0.1 mg to 1.0 mg ipratropium; (j) sealing each of the one or more dispensing containers containing the solution; and (k) wherein the stability of the solution is such that the shelf-life of the solution in the one or more dispensing vials is more than 12 months.
- 25. The method of claim 24, wherein the step of adding the osmotic adjusting agent comprises adding the agent selected from the group consisting of sodium chloride, potassium chloride, zinc chloride, calcium chloride and mixtures thereof.
- 26. The method of claim 24, wherein the step of adding the osmotic adjusting agent comprises adding sodium chloride.
- 27. The method of claim 24, wherein the step of adding the osmotic adjusting agent comprises adding said agent selected from the group consisting of mannitol, glycerol, dextrose or mixtures thereof.
- 28. The method of claim 24, wherein the step of adding the osmotic agent comprises adding sufficient osmotic agent so that the solution in the one or more dispensing vials comprises about 0.4 wt. % to about 1.0 wt. % ionic salt.
- 29. The method of claim 24, wherein the step of adding the osmotic adjusting agent requires adding sufficient agent so that the solution in the one or more dispensing vials comprises about 0.01% to about 2.0 wt. % of said agent.
- 30. The method of claim 24, further comprising the step packaging the one or more dispensing vials in an aluminum foil pouch.
- 31. The method of claim 24, wherein the step of adding albuterol and ipratropium requires that sufficient albuterol and ipratropium be added so that the solution in the one or more dispensing vials comprises about 0.083 wt. % albuterol and 0.01 wt. % ipratropium bromide.
- 32. The method of claim 24, wherein the step of filling the one or more dispensing vials comprises filling the vials with 3 ml of the solution into the one or more vials; and wherein the step of adding the water into the container comprises adding the water at a temperature between about 18° C. and 25° C.
- 33. The method of claim 24, wherein the step of filling the one or more dispensing vials comprises filling the vials with about 2.84 ml to about 3.30 ml of the solution into the one or more vials.
- 34. The method of claim 24, further comprising the step of passing the solution through a first sterilizing filter.
- 35. The method of claim 34, further comprising the step of passing the solution through a second sterilizing filter.
- 36. A method of making a premixed, premeasured inhalation solution for treating bronchospasm in patients suffering from chronic obstructive pulmonary disease; said method comprising the steps:
(a) placing a unit dose of a therapeutically effective amount of albuterol and ipratropium bromide in a vehicle, wherein the concentration of albuterol in the vehicle ranges from about 0.60 mg to about 5.0 mg and the concentration of the ipratropium bromide in the carrier ranges from 0.01 mg to 1.00 mg; and (b) adding hydrochloric acid to adjust the pH of the inhalation solution to a level ranging from about 3.0 to about 4.0. (c) adding an osmotic agent to adjust the isotonicity of the inhalation solution; wherein the osmotic adjusting agent is selected from the group consisting of sodium chloride, potassium chloride, zinc chloride, calcium chloride and mixtures thereof. (d) sterilizing the inhalation solution by passing it through a filter or by steam sterilization; and (e) providing the inhalation solution in a single container, wherein the inhalation solution in the single container comprises about 2.5 mg albuterol and 0.5 ipratropium bromide.
Priority Claims (1)
Number |
Date |
Country |
Kind |
PCT/US02/33353 |
Oct 2002 |
WO |
|
I. CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. application Ser. No. 10/162,460, filed Jun. 3, 2002, which is a continuation-in-part of U.S. application Ser. No. 10/034,657, filed Dec. 28, 2001 (now abandoned), and International Application PCT/US02/33353, filed Oct. 18, 2002 which both claim priority under 35 U.S.C. § 119 from U.S. Provisional Application Serial No. 60/346,078, filed Oct. 26, 2001. The entire disclosure of each of these prior applications is incorporated herein by reference in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60346078 |
Oct 2001 |
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
10162460 |
Jun 2002 |
US |
Child |
10417726 |
Apr 2003 |
US |
Parent |
10034657 |
Dec 2001 |
US |
Child |
10162460 |
Jun 2002 |
US |