Bronchodilating β-agonist compositions and methods
View Patent ↗Bronchodilating compositions and methods are provided. The compositions are intended for administration as a nebulized aerosol. In certain embodiments, the compositions contain formoterol, or a derivative thereof. Methods for treatment, prevention, or amelioration of one or more symptoms of bronchoconstrictive disorders using the compositions provided herein are also provided.
1. A sterile unit dose, comprising:
(a) about 0.1 mL to about 3.0 mL of a pharmaceutical composition comprising formoterol or a salt thereof at a concentration of from about 0.08 μg/mL to about 34 μg/mL based on formoterol free base, in a pharmacologically suitable solution, wherein the composition further comprises water and a buffer selected from the group consisting of citric acid/phosphate buffer, acetate buffer, citrate buffer and phosphate buffer at a concentration of from about 1 mM to about 20 mM, said composition having a pH of between about 4.5 and about 5.5 and having an estimated shelf life of greater than 90% after 3 months storage at 25° C. and after 3 years storage at 5° C.;
(b) packaged in pharmaceutical packaging material.
2. A sterile unit dose, comprising:
(a) about 0.1 mL to about 3.0 mL of a pharmaceutical composition comprising formoterol or a salt thereof at a concentration of from about 0.08 μg/mL to about 34 μg/mL based on formoterol free base, in a pharmacologically suitable solution, wherein the composition further comprises water and a buffer selected from the group consisting of citric acid/phosphate buffer, acetate buffer, citrate buffer and phosphate buffer at a concentration of from about 5 mM to about 20 mM, said composition having a pH of between about 4.5 and about 5.5 and having an estimated shelf life of greater than about 94% after 3 months storage at 25° C. and greater than about 96% after 3 months storage at 5° C.;
(b) packaged in pharmaceutical packaging material.
3. A sterile unit dose, comprising:
(a) about 2 mL of a pharmaceutical composition comprising formoterol or a salt thereof at a concentration of from about 0.08 μg/mL to about 26 μg/mL based on formoterol free base, in a pharmacologically suitable solution, wherein the composition further comprises water and a citrate buffer at a concentration of from about 1 mM to about 20 mM, said composition having a pH of about 5, and having an estimated shelf life of greater than about 94% after 3 months storage at 25° C. and greater than about 96% after 3 months storage at 5° C.;
(b) packaged in a vial over wrapped with a laminate.
4. A sterile unit dose, comprising:
(a) about 2 mL of a pharmaceutical composition comprising formoterol or a salt thereof at a concentration of from about 0.08 μg/mL to about 26 μg/mL based on formoterol free base, in a pharmacologically suitable solution, wherein the composition further comprises water and a citrate buffer at a concentration of from about 1 mM to about 50 mM, said composition having a pH of about 5;
(b) packaged in a vial over wrapped with a laminate.
5. The sterile unit dose as in any one of claims 1 , 2 , 3 or 4 further comprising a tonicity adjusting agent.
6. The sterile unit dose of claim 5 wherein said tonicity adjusting agent is sodium chloride.
7. The sterile unit dose as in any one of claims 1 or 2 wherein said pharmaceutical packaging material is selected from the group consisting of blister packs, bottles, tubes, inhalers, pumps, bags, vials, containers and syringes.
8. A method of oral administration comprising the steps of:
(a) adding to a nebulizer, from a propellant-free, sterile unit dose package about 1 to about 3 mL of a pharmaceutical composition comprising formoterol or a salt thereof at a concentration of from about 0.08 μg/mL to about 34 μg/mL based on formoterol free base, in a pharmacologically suitable solution, wherein the composition further comprises water and a buffer selected from the group consisting of citric acid/phosphate buffer, acetate buffer, citrate buffer and phosphate buffer at a concentration of from about 1 mM to about 50 mM, said composition having a pH of between about 4.5 and about 5.5; and
(b) directly administering said composition to a subject in need thereof, without dilution or other modification of said composition prior to administration.
9. A method of oral administration comprising the steps of:
(a) adding to a nebulizer from a propellant-free, sterile unit dose package about 1 to about 3 mL of a pharmaceutical composition comprising formoterol or a salt thereof at a concentration of from about 0.08 μg/mL to about 34 μg/mL based on formoterol free base, in a pharmacologically suitable solution, wherein the composition further comprises water and a buffer selected from the group consisting of citric acid/phosphate buffer, acetate buffer, citrate buffer and phosphate buffer at a concentration of from about 1 mM to about 50 mM, said composition having a pH of between about 4.5 and about 5.5 and having an estimated shelf life of greater than 90% after 3 months storage at 25° C. and after 3 years storage at 5° C.; and
(b) directly administering said composition to a subject in need thereof, without dilution or other modification of said composition prior to administration.
10. A method of oral administration comprising the steps of:
(a) adding from a propellant-free, sterile unit dose package to a nebulizer about 2 mL of a pharmaceutical composition comprising formoterol or a salt thereof at a concentration of from about 0.08 μg/mL to about 26 μg/mL based on formoterol free base, in a pharmacologically suitable solution, wherein the composition further comprises water and a citrate buffer at a concentration of from about 1 mM to about 20 mM, said composition having a pH of about 5 and having an estimated shelf life of greater than about 94% after 3 months storage at 25° C. and greater than about 96% after 3 months storage at 5° C.; and
(b) directly administering said composition to a subject in need thereof, without dilution or other modification of said composition prior to administration.
11. The method of claims 8 , 9 , or 10 further comprising a tonicity adjusting agent.
12. The method of claim 11 wherein said tonicity adjusting agent is sodium chloride.
13. The method as in any one of claims 8 , 9 or 10 wherein said package is selected from the group consisting of blister packs, bottles, tubes, inhalers, pumps, bags, vials, containers and syringes.
14. The method as in any one of claims 8 , 9 or 10 wherein said package is a vial.
15. The method of claim 14 wherein said vial is over wrapped with a laminate.
16. The sterile unit dose of claim 1 wherein said formoterol is in the (R) form, or a salt thereof.
17. The sterile unit dose of claim 16 wherein said (R) formoterol is a salt and said salt is a tartrate.
18. The sterile unit dose of claim 1 wherein said formoterol is a tartrate salt.