Aerosol formulation for COPD
Inventors
BONELLI, Sauro • Usberti, Francesca • Zambelli, Enrico
Assignees
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Publication Number
US-12357568-B2
Publication Date
2025-07-15
Expiration Date
Abstract
Stable aerosol solution formulations comprising glycopyrronium bromide are useful for administration to patients with COPD and other respiratory conditions.
Core Innovation
The invention relates to stable pMDI aerosol solution formulations for chronic obstructive pulmonary disease in which glycopyrronium bromide is dissolved in HFA propellant together with ethanol as a co-solvent. The formulation includes a stabilizing amount of inorganic acid in the form of hydrochloric acid equivalent to 0.005 to 1.0 μg/μcl of 1M hydrochloric acid, while glycopyrronium bromide is present at 0.015 to 0.04% w/w. The formulation further comprises ethanol at 10 to 15% w/w and HFA-134a at 85 to 90% w/w.
The problem addressed is degradation of glycopyrronium under high temperature/humidity conditions when the formulation lacks sufficient inorganic acid stabilizer. The disclosed compositions prevent observed degradation by including the specified hydrochloric-acid equivalent level, thereby maintaining formulation stability. An acid-concentration range study identifies failure at too low and too high hydrochloric-acid equivalent amounts, with no significant degradation reported when using the stabilized acid range.
In addition to the acid-stabilized pMDI composition, the document describes integration into a pressurized metered dose inhaler and use of the formulated aerosol for inhalation therapy of obstructive respiratory disorders. Quantitative formulation ranges and performance/stability targets are provided, including improvements in fine particle fraction and storage stability. The document also includes options for glycopyrronium bromide stereoisomer forms, and optional excipients are discussed as low-volatility components or water.
Claims Coverage
The document contains one independent claim directed to a pharmaceutical composition for use with a pressurized metered dose inhaler, having multiple inventive features.
Hydrochloric acid stabilized glycopyrronium pMDI composition
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/μcl of 1M hydrochloric acid.
Specific glycopyrronium, ethanol, and HFA-134a composition ranges
In the composition, glycopyrronium bromide is in an amount of 0.015 to 0.04% w/w, ethanol is in an amount of 10 to 15% w/w, and HFA-134a is in an amount of 85 to 90% w/w.
Combination with formoterol fumarate and beclometasone dipropionate
The composition comprises formoterol fumarate and the composition comprises beclometasone dipropionate.
Overall, claim coverage is focused on a pressurized metered dose inhaler pharmaceutical composition that stabilizes glycopyrronium bromide in an HFA-134a/ethanol system using a defined hydrochloric-acid equivalent amount, while also specifying quantitative formulation ranges and including formoterol fumarate and beclometasone dipropionate.
Stated Advantages
Prevents degradation of glycopyrronium under high temperature/humidity conditions when inorganic acid stabilizer is included.
Maintains formulation stability as indicated by reported storage stability targets.
Provides improvements in fine particle fraction (FPF) and/or fine particle dose (FPD), as described in the document summary.
Documented Applications
Inhalation use for COPD, including administration of the disclosed pMDI composition to a subject in need.
Inhalation use for asthma, including administration of the disclosed pMDI composition to a subject in need.
Use for other obstructive respiratory disorders, as described in the document summary.
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