COPD Inhaler Formulation Stabilization with HCl
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Solution Overview
Problem
Current pharmaceutical aerosol formulations of glycopyrronium chloride and formoterol are unstable under high temperature and humidity conditions, leading to significant degradation of formoterol and the formation of unwanted degradation products, making them clinically and commercially non-viable.
Innovation Solution
Incorporating an optimized amount of 1M HCl (0.1-0.3 µg/µl) in the formulation, along with removing oxygen from the canister headspace, stabilizes both glycopyrronium chloride and formoterol, ensuring consistent delivery over an extended period.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pharmaceutical aerosol formulations of glycopyrronium chloride and formoterol are stored under high temperature and humidity conditions, then the formulation remains stable initially, but significant degradation of formoterol occurs and unwanted degradation products form
Solution Approach 1:
The patent introduces HCl as an intermediary substance that mediates between the active ingredients and the degrading environment. The HCl maintains an acidic environment that prevents hydrolysis and degradation of formoterol and glycopyrronium chloride, acting as a protective mediator against temperature and humidity-induced degradation
Solution Approach 2:
The patent creates an inert chemical environment by establishing acidic conditions with HCl that are chemically resistant to degradation. This inert environment protects the active ingredients from reacting with water or oxygen during storage under high temperature and humidity conditions
2Duration of action of stationary object
If the formulation is designed for extended period delivery, then consistent dosing is achieved, but stability under high temperature and humidity deteriorates
Solution Approach 1:
The patent applies preliminary action by adding HCl to the formulation before storage, which preemptively establishes protective acidic conditions. This preliminary stabilization prevents degradation from occurring during extended storage periods under high temperature and humidity, enabling consistent dosing over time
Solution Approach 2:
The patent changes the chemical parameter of the formulation by introducing HCl to create an acidic environment. This parameter change from neutral to acidic conditions fundamentally alters the stability characteristics of the formulation, enabling it to maintain reliability during extended storage under harsh conditions
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 stabilization of formoterol and glycopyrronium chloride results in a stable aerosol formulation that maintains effective dosing for an extended period, meeting clinical and commercial viability standards, with reduced levels of degradation products below identification thresholds.
Implementation Method 1
Incorporating an optimized amount of 1M HCl (0.1-0.3 µg/µl) in the formulation, along with removing oxygen from the canister headspace, stabilizes both glycopyrronium chloride and formoterol
Implementation Method 2
pharmaceutical aerosol solution formulations intended for use with pressurized metered dose inhalers
Implementation Method 3
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 chloride 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 chloride and the formoterol components. Optionally the formulation further comprises beclometasone dipropionate.