Pharmaceutical composition
A pharmaceutical composition is described. The composition comprises: (i) a drug component comprising at least one pharmaceutically acceptable salt of giycopyrrolate; and (ii) a propellant component comprising 1,1-difluoroethane (HFA-152a).
1. A pharmaceutical composition for a metered dose inhaler comprising:
a drug component consisting of glycopyrronium bromide, fluticasone propionate and optionally at least one long acting beta-2-agonist selected from the group consisting of indacaterol and indacaterol maleate; and
(ii) a propellant component comprising 1,1-difluoroethane (HFA-152a), wherein the composition contains greater than 0.5 ppm and less than 500 ppm of water based on the total weight of the pharmaceutical composition.
2. A pharmaceutical composition for a metered dose inhaler comprising (i) a drug component consisting of glycopyrronium bromide, fluticasone propionate and optionally at least one long acting beta-2-agonist selected from the group consisting of indacaterol and indacaterol maleate; and (ii) a propellant component comprising 1,1-difluoroethane (HFA-152a), wherein the composition contains greater than 0.5 ppm, and less than 1000 ppm of oxygen based on the total weight of the pharmaceutical composition.
3. The pharmaceutical composition of claim 1 , wherein the drug component includes at least one long acting beta-2-agonist (LABA) selected from the group consisting of indacaterol and indacaterol maleate.
4. The pharmaceutical composition of claim 3 , wherein the drug component includes indacaterol.
5. The pharmaceutical composition of any ore of the claim 1 , wherein at least 99 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).
6. The pharmaceutical composition of claim 1 , wherein the propellant component is entirely 1,1-difluoroethane (HFA-152a).
7. The pharmaceutical composition of claim 5 , wherein the propellant component contains from 0.5 to 10 ppm of unsaturated impurities.
8. The pharmaceutical composition of claim 1 , further comprising a surfactant component comprising at least one surfactant compound.
9. The pharmaceutical composition of claim 1 , further comprising a polar excipient.
10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition free of one or more of the following: (i) acid stabilizers; (ii) perforated microstructures; (iii) polar excipients; and (iv) ethanol.
11. The pharmaceutical composition of claim 1 , wherein the composition after storage in uncoated aluminum containers at 25° C. and 60% relative humidity for 3 months will produce less than 8% by weight of impurities from the degradation of the glycopyrronium bromide based on the total weight of the glycopyrronium bromide and the impurities.
12. The pharmaceutical composition of claim 1 , wherein the composition after storage in uncoated aluminum containers at 40° C. and 75% relative humidity for 3 months will produce less than 1.0% by weight of impurities from the degradation of the glycopyrronium bromide based on the total weight of the glycopyrronium bromide and the impurities.
13. The pharmaceutical composition of claim 1 , wherein at least 96.0% by weight of the glycopyrronium bromide that is contained originally in the pharmaceutical composition immediately following preparation will be present in the composition after storage in uncoated aluminum containers at 25° C. and 60% relative humidity for 3 months and after storage in uncoated aluminum containers at 40° C. and 75% relative humidity for 3 months.
14. The pharmaceutical composition of claim 1 , wherein the composition when delivered from a metered dose inhaler yields a fine particle fraction of the glycopyrronium bromide which is at least 40 weight % of the emitted dose of the glycopyrronium bromide.
15. The pharmaceutical composition of claim 1 , wherein the composition is in the form of a suspension.
16. The pharmaceutical composition of claim 1 , wherein the composition is in the form of a solution.
17. A metered dose inhaler (MDI) fitted with a sealed and pressurized aerosol container containing a pharmaceutical composition as claimed in claim 1 .
18. The pharmaceutical composition of claim 1 , wherein the composition is adapted to deliver the compounds making up the drug component in approximately the same proportions that they occur in the pharmaceutical composition.
19. The pharmaceutical composition of claim 4 , wherein the fine particle fraction of each drug in the emitted dose when the pharmaceutical composition is delivered from a metered dose inhaler is at least 40 weight % of the emitted dose of that drug.
20. The pharmaceutical composition of claim 19 , wherein the fine particle fractions of the glycopyrronium bromide, indacaterol and fluticasone propionate in the emitted dose are observed after storage for 1 month at 40° C. and 75% relative humidity.
21. The pharmaceutical composition of claim 1 , wherein at least 90 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).
22. The pharmaceutical composition of claim 1 , wherein at least 95 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).
23. The pharmaceutical composition of claim 8 , wherein the at least one surfactant compound is selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol surfactants, oleic acid and lecithin.
24. The pharmaceutical composition of claim 9 , wherein the polar excipient is ethanol.
25. The pharmaceutical composition of claim 2 , wherein the drug component includes at least one long acting beta-2-agonist (LABA) selected from the group consisting of indacaterol and indacaterol maleate.
26. The pharmaceutical composition of claim 25 , wherein the drug component includes indacaterol.
27. The pharmaceutical composition of claim 2 , wherein at least 99 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).
28. The pharmaceutical composition of claim 2 , wherein at least 90 weight % of the propellant component is 1,1-difluoroethane (HFA-152a).