HFO-1234ze(E) pMDI Suspension Formulation for Stable Dose Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing pressurized metered dose inhalers (pMDIs) rely on hydrofluoroalkanes (HFAs) as propellants, which have a high global warming potential, and alternative propellants like hydrofluoroolefins (HFOs) and carbon dioxide have not been successfully commercialized, necessitating a more environmentally friendly and effective propellant solution.
Innovation Solution
Development of pMDIs using HFO-1234ze(E) as the primary propellant, combined with ethanol and active pharmaceutical ingredients (APIs) to form stable suspension formulations, addressing issues of physical and chemical stability, and minimizing API deposition on inhaler surfaces.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If hydrofluoroalkanes (HFAs) are used as propellants in pMDIs, then effective aerosolization and dose delivery are achieved, but high global warming potential results
Solution Approach 1:
The patent changes the chemical composition parameters of the propellant system by incorporating HFO-1234ze(E) at greater than 70% by weight, combined with ethanol and API suspension. This parameter change maintains aerosolization effectiveness while achieving low GWP (less than 1), directly resolving the contradiction between reliability and environmental harm.
Solution Approach 2:
The patent creates a composite propellant system combining HFO-1234ze(E), ethanol, and suspended API particles. This composite formulation leverages the low GWP of HFO-1234ze(E) while using ethanol as a co-solvent to maintain suspension stability, achieving both environmental benefits and functional performance.
2Object-affected harmful factors
If alternative propellants like HFOs or CO2 are used, then lower global warming potential is achieved, but successful commercialization and product development have not been realized
Solution Approach 1:
The patent optimizes the propellant concentration parameter by using greater than 70% HFO-1234ze(E) by weight, which provides sufficient vapor pressure and propelling force for reliable aerosol generation. This parameter optimization, combined with ethanol co-solvent, enables successful product commercialization with low GWP.
Solution Approach 2:
The patent introduces ethanol as an intermediary substance that facilitates the suspension of API particles in the HFO-1234ze(E) propellant system. This intermediary component ensures physical and chemical stability of the formulation, enabling successful product development and commercialization of HFO-based pMDIs.
3Object-affected harmful factors
If suspension formulations are used with HFO-1234ze(E), then low global warming potential and effective aerosolization are achieved, but physical and chemical stability challenges arise
Solution Approach 1:
The patent develops a composite suspension formulation containing HFO-1234ze(E), ethanol, and suspended API particles. This composite system achieves low GWP while maintaining physical and chemical stability through the synergistic interaction between the propellant and ethanol co-solvent, resolving the stability challenge.
Solution Approach 2:
Ethanol serves as an intermediary substance that enhances the stability of API suspension in HFO-1234ze(E). The ethanol co-solvent prevents particle aggregation and maintains uniform distribution, addressing the physical stability challenges inherent in suspension formulations with alternative propellants.
4Reliability
If suspension formulations are used, then effective medicament delivery is achieved, but API deposition on inhaler surfaces increases
Solution Approach 1:
The patent optimizes the formulation parameters by using HFO-1234ze(E) with greater than 70% by weight and incorporating ethanol as a co-solvent. This parameter change modifies the surface properties and flow characteristics of the suspension, reducing API adhesion to inhaler surfaces while maintaining effective medicament delivery to the respiratory tract.
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
HFO-1234ze(E) pMDIs offer a low global warming potential while maintaining effective aerosolization and dose delivery, ensuring consistent and stable medicament delivery over time.
Implementation Method 1
Delivery of aerosolized medicament to the respiratory tract for the treatment of respiratory and other diseases can be done using, by way of example, pressurized metered dose inhalers (pMDI)
Implementation Method 2
the canister includes a formulation (i.e., composition), the formulation including greater than 70% by weight of propellant HFO-1234ze(E), ethanol, and at least one active pharmaceutical ingredient (API) suspended in the formulation to form a suspension
Data Source
AI summary
Various embodiments of a metered dose inhaler are disclosed. The inhaler includes a metering valve, a canister, and an actuator having an actuator nozzle. The canister includes a formulation having greater than 70% by weight of HFO-1234ze(E), and at least one active pharmaceutical ingredient suspended in the formulation to form a suspension.