Epinephrine MDI Suspension Using HFO Propellant for Low-GWP Delivery
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Solution Overview
Problem
Existing epinephrine metered dose inhaler (MDI) formulations using hydrofluoroalkane (HFA) propellants contribute to global warming and ozone depletion, necessitating a more environmentally friendly alternative without compromising efficacy and safety.
Innovation Solution
A stable suspension formulation using hydrofluoroolefin (HFO-1234ze) as a propellant, combined with pre-micronized epinephrine, ethanol as a co-solvent, and polysorbate 80 as a surfactant, to create a pressurized MDI for bronchial asthma treatment, ensuring comparable efficacy and safety while reducing environmental impact.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If HFA propellants are used in epinephrine MDI formulations, then therapeutic efficacy and safety are maintained, but global warming potential and ozone depletion occur
Solution Approach 1:
The patent changes the propellant parameter from HFA (high GWP) to HFO-1234ze (low GWP), maintaining the functional properties needed for therapeutic efficacy while eliminating the harmful environmental effects. The HFO propellant provides similar vapor pressure and density characteristics to HFA but with a GWP of only 6 compared to 1300-2900 for HFA propellants.
Solution Approach 2:
The patent employs a disposable MDI device containing the epinephrine suspension formulation with HFO propellant. The entire device is designed for single use, eliminating the need for refilling or reuse, which simplifies the environmental impact assessment and ensures consistent formulation properties throughout the product lifecycle.
2Object-generated harmful factors
If HFO propellant is used to reduce environmental impact, then global warming potential decreases, but formulation stability and drug delivery consistency may be compromised
Solution Approach 1:
The patent introduces ethanol as a co-solvent and polysorbate 80 as a surfactant to mediate between the HFO propellant and epinephrine. These intermediaries facilitate the formation of a stable suspension by improving wettability, preventing particle aggregation, and ensuring uniform drug distribution throughout the aerosol formulation.
Solution Approach 2:
The patent creates a composite aerosol formulation combining HFO propellant, epinephrine, ethanol, and polysorbate 80. This composite system leverages the complementary properties of each component: the low GWP characteristic of HFO, the solubilizing capability of ethanol, and the surfactant properties of polysorbate 80, achieving both environmental and formulation stability goals.
3Productivity
If pre-micronized epinephrine is used to improve respirable drug delivery, then fine particle mass deposition increases, but manufacturing complexity increases
Solution Approach 1:
The patent performs the micronization of epinephrine particles before formulation, creating pre-micronized epinephrine with optimized particle size distribution (D10, D50, D90 values). This preliminary action ensures that when the epinephrine is incorporated into the MDI formulation and aerosolized, it delivers optimal fine particle mass to the respiratory tract, improving drug delivery efficiency.
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 HFO-1234ze-based formulation achieves higher fine particle mass deposition and fewer impurities, maintaining therapeutic effectiveness with a negligible contribution to global warming and ozone depletion, meeting storage requirements and ensuring consistent drug delivery.
Implementation Method 1
aerosol formulations for the delivery of medications suitable for administration via the respiratory tract
Implementation Method 2
pressurized metered dose inhaler (MDI)
Implementation Method 3
surfactant, and hydrofluoroolefin (HFO) propellant
Implementation Method 4
stable suspension formulation containing epinephrine
Implementation Method 5
HFA propellants are formidable greenhouse gases that absorb infrared radiation and trap heat in the Earth's atmosphere resulting in a rise in global temperatures via the greenhouse effect
Implementation Method 6
Epinephrine is approved to be used as a bronchodilator in the treatment of acute bronchial asthma
Data Source
AI summary
Pharmaceutical aerosol formulations containing pre-micronized epinephrine, co-solvent ethanol, surfactant polysorbate 80, and propellant trans-1,3,3,3-tetrafluoropropene (HFO-1234ze(E)) for use in a pressurized metered dose inhaler is described. The formulations provide a highly efficient delivery of pre-micronized epinephrine particles into the patients' respiratory tracts and have the advantages of high efficacy, improved safety, and a low global warming potential (GWP) for environmental impact.