Indacaterol MDI Propellant Stability and GWP Reduction
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Solution Overview
Problem
Current pharmaceutical compositions for indacaterol, used in metered dose inhalers (MDIs), face challenges with limited physical and chemical stability, and high global warming potential propellants like HFA-134a and HFA-227ea, making it difficult to deliver indacaterol effectively while minimizing environmental impact.
Innovation Solution
A pharmaceutical composition using 1,1-difluoroethane (HFA-152a) as the primary propellant, with low water and oxygen content, to improve chemical stability, aerosolization performance, and reduce global warming potential, allowing for stable suspension and delivery of indacaterol and glycopyrrolate in MDIs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If HFA-134a or HFA-227ea propellants are used in MDIs, then the propellant can effectively deliver the drug formulation, but the global warming potential increases significantly
Solution Approach 1:
The patent changes the chemical composition parameters of the propellant from HFA-134a or HFA-227ea to HFA-152a, which has lower global warming potential while maintaining the necessary physical properties (vapour pressure, boiling point) for effective MDI drug delivery
Solution Approach 2:
The patent adopts a propellant (HFA-152a) that is environmentally friendlier and can be used in a single-use or limited-use context, reducing long-term environmental accumulation of high-GWP substances
2Ease of operation
If indacaterol is formulated for MDI delivery, then the drug can be delivered to the respiratory tract, but the chemical stability is limited
Solution Approach 1:
The patent uses HFA-152a propellant as an intermediary medium that provides chemical stability to indacaterol during storage and delivery, while also enabling the aerosolization and respiratory delivery of the drug
Solution Approach 2:
The patent creates a chemically inert environment using HFA-152a propellant that prevents degradation of indacaterol, maintaining drug stability throughout the shelf life and during actuation of the MDI device
3Stability of the object's composition
If the propellant density is increased to prevent drug particle sinking, then the drug suspension remains homogeneous, but the aerosolization performance may be affected
Solution Approach 1:
The patent optimizes the density parameter of the propellant by selecting HFA-152a, which has a density (0.86 g/cm³) that closely matches the drug particles, preventing rapid sinking or floating while maintaining excellent aerosolization characteristics through its optimal vapour pressure and boiling point
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 use of HFA-152a propellant enhances the chemical stability and aerosolization performance of indacaterol, maintaining high fine particle fraction delivery even after storage, reducing impurities and ensuring effective treatment of respiratory disorders with reduced environmental impact.
Implementation Method 1
it needs to have a number of properties. These include an appropriate boiling point and vapour pressure so that it can be liquefied in a closed container at room temperature but develop a high enough pressure when the MDI is activated to deliver the drug as an atomised formulation
Implementation Method 2
These include an appropriate boiling point and vapour pressure so that it can be liquefied in a closed container at room temperature but develop a high enough pressure when the MDI is activated
Implementation Method 3
When the drug is in suspension in the propellant, the density of the liquid propellant is desirably similar to that of the solid drug in order to avoid rapid sinking or floating of the drug particles in the liquid
Implementation Method 4
it should form a non-flammable or low flammability mixture when mixed with air in the respiratory tract
Data Source
AI summary
A pharmaceutical composition is described. The composition comprises: (i) a drug component comprising at least one indacaterol compound selected from indacaterol and indacaterol maleate and at least one pharmaceutically acceptable salt of glycopyrrolate; and (ii) a propellant component at least 90 weight % of which is 1,1-difluoroethane (HFA-152a).