COPD Inhaler Formulation Stabilization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Aerosol solutions of formoterol fumarate are unstable and have a short shelf-life when stored under suboptimal conditions, and glycopyrronium bromide is unstable in HFA-based aerosol solutions, leading to significant degradation of formoterol and the formation of unwanted degradation products, making existing formulations clinically and commercially non-viable.
Innovation Solution
Incorporating an optimized amount of 1M HCl (0.1-0.245 µg/µl) and using ethanol as a co-solvent in a pressurized metered dose inhaler formulation with glycopyrronium bromide and formoterol, along with beclometasone dipropionate, to stabilize both components and reduce degradation products, while removing oxygen from the canister headspace to further stabilize formoterol.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If glycopyrronium bromide is formulated in HFA-based aerosol solutions, then it provides effective bronchodilation, but it becomes unstable and degrades significantly
Solution Approach 1:
The patent changes the chemical parameters of the formulation by introducing a co-solvent system (ethanol/water) and adjusting pH to 4.0-6.0, which stabilizes glycopyrronium bromide in the aerosol solution and prevents degradation while maintaining therapeutic efficacy
Solution Approach 2:
The patent introduces a co-solvent system (ethanol and water) as an intermediary medium between glycopyrronium bromide and the HFA propellant, which prevents direct incompatibility and stabilizes the active ingredient against degradation
2Reliability
If formoterol fumarate is formulated in aerosol solutions without optimization, then it provides bronchodilation, but it has short shelf-life and degrades under suboptimal storage conditions
Solution Approach 1:
The patent optimizes formulation parameters including pH (4.0-6.0), alcohol content (5-50% v/v), and the presence of glycopyrronium bromide, which collectively stabilize formoterol fumarate and extend shelf-life under various storage conditions while maintaining bronchodilator efficacy
Solution Approach 2:
The patent incorporates stabilizing excipients and optimizes the formulation composition beforehand to prevent degradation of formoterol fumarate, providing protection against hydrolysis and oxidation that would occur during storage and use
3Reliability
If glycopyrronium bromide and formoterol are combined in aerosol solutions, then they provide synergistic bronchodilation, but unwanted degradation products form
Solution Approach 1:
The patent adjusts the formulation parameters including pH (4.0-6.0), alcohol content (5-50% v/v), and the ratio of co-solvents to stabilize both active ingredients simultaneously, preventing unwanted degradation reactions while maintaining synergistic bronchodilator effect
Solution Approach 2:
The patent uses a co-solvent system (ethanol/water) as an intermediary medium that is compatible with both glycopyrronium bromide and formoterol fumarate, preventing incompatibility reactions and degradation product formation between the two active ingredients
4Stability of the object's composition
If special storage conditions are imposed on the formulation, then stability is improved, but ease of operation and commercial viability are reduced
Solution Approach 1:
The patent formulates the aerosol with pH adjustment (4.0-6.0), co-solvent system (5-50% v/v ethanol), and optimized excipient composition to achieve stability under normal storage conditions, eliminating the need for special refrigeration or handling requirements and improving commercial viability
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The formulation ensures consistent delivery of active ingredients over an extended period, maintaining stability and reducing degradation products, thereby extending the product's shelf-life and ensuring effective dosing without the need for special storage conditions.
Implementation Method 1
the composition contains an amount of 1M HCl in the range 0.1-0.245 µg/µl
Implementation Method 2
the co-solvent is ethanol in a concentration range from 5 to 25% (w/w)
Implementation Method 3
pharmaceutical aerosol solution formulations intended for use with pressurized metered dose inhalers
Data Source
AI summary
The invention concerns an aerosol formulation suitable for administering to COPD patients by means of a pressurized metered dose inhaler (pMDI), comprising glycopyrronium bromide in combination with formoterol. The formulation further comprises a HFA propellant, a co-solvent, and an amount of inorganic acid sufficient to stabilize both the glycopyrronium bromide and the formoterol components. Optionally the formulation further comprises beclometasone dipropionate.