Aerosol formulation for COPD
Stable aerosol solution formulations comprising glycopyrronium bromide are useful for administration to patients with COPD and other respiratory conditions.
1. A pharmaceutical composition for use with a pressurized metered dose inhaler, comprising glycopyrronium bromide dissolved in HFA-134a and ethanol, wherein:
the composition comprises an amount of hydrochloric acid equivalent to 0.005 to 1.0 μg/μl of 1M hydrochloric acid;
the composition comprises glycopyrronium bromide in an amount of 0.015 to 0.04% w/w of the composition;
the composition comprises ethanol in an amount of 10 to 15% w/w of the composition; and
the composition comprises HFA-134a in an amount of 85 to 90% w/w of the composition.
2. A composition according to claim 1 , comprising an amount of hydrochloric acid equivalent to 0.18 to 0.32 μg/μl 1M hydrochloric acid.
3. A composition according to claim 1 , comprising one or more pharmaceutically active ingredients selected from the group consisting of beta-2-agonists, corticosteroids, antimuscarinic agents, and phosphodiesterase (IV) inhibitors.
4. A composition according to claim 3 , comprising formoterol fumarate.
5. A composition according to claim 3 , comprising beclometasone dipropionate.
6. A metered dose inhaler, comprising a pharmaceutical composition according to claim 1 .
7. A kit-of-parts, comprising:
a pharmaceutical composition according to claim 1 ; and
one or more pharmaceutically active ingredients for separate, sequential, or simultaneous administration;
wherein the one or more pharmaceutically active ingredients are selected from the group consisting of beta-2-agonists, corticosteroids, antimuscarinic agents, and phosphodiesterase (IV) inhibitors.
8. A composition according to claim 1 , wherein the composition comprises an amount of hydrochloric acid equivalent to 0.099 to 0.74 μg/μl of 1M hydrochloric acid.
9. A metered dose inhaler according to claim 6 , comprising a metering valve capable of delivering a volume of about 63 μl per actuation.
10. A composition according to claim 1 , wherein the glycopyrronium bromide is the racemic mixture (3S,2′R),(3R,2′S)-3-[(cyclopentylhydroxyphenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide.
11. A composition according to claim 1 , comprising water in an amount less than 0.5% w/w of the composition.
12. A composition according to claim 1 , comprising water in an amount 0.005 to 0.5% w/w of the composition.
13. A composition according to claim 1 , wherein the composition is free of excipients other than the ethanol, the HFA-134a, and the hydrochloric acid.