Fluticasone MDI Formulations Using HFO-1234ze(E) Against Flocculation
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Solution Overview
Problem
Existing metered dose inhalers (MDIs) face challenges in delivering fluticasone effectively due to aggregation and flocculation of API particles, requiring multiple actuations to achieve the desired dosage, and there is a need for environmentally friendly carriers that maintain stability and reproducibility of high API concentrations.
Innovation Solution
The use of HFO-1234ze(E) as a carrier with ethanol and optionally polyethylene glycol (PEG) to suspend fluticasone particles, with specific weight percentages to prevent flocculation and ensure stable, reproducible delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the amount of API in the suspension is increased to deliver the desired dosage in a single actuation, then the productivity is improved, but the suspension stability deteriorates due to increased flocculation and aggregation
Solution Approach 1:
The patent introduces HFO-1234ze(E) as an intermediary carrier substance that mediates between the API particles and the environment. This carrier prevents direct interaction between API particles that would cause aggregation, while also providing the necessary propellant properties for single actuation delivery. The carrier acts as a protective medium that maintains particle dispersion.
Solution Approach 2:
The patent changes the physical and chemical parameters of the carrier system by selecting HFO-1234ze(E) with specific properties (vapor pressure, boiling point, chemical stability) that optimize both suspension stability and delivery performance. The ethanol co-solvent parameter is adjusted to fine-tune the suspension characteristics and prevent flocculation.
2Reliability
If conventional carriers are used to maintain suspension stability, then the reliability is improved, but the environmental harm increases due to ozone depletion and global warming
Solution Approach 1:
The patent changes the chemical composition parameters of the carrier by replacing ozone-depleting substances with HFO-1234ze(E), which has zero ozone depletion potential and low global warming potential. This parameter change maintains the necessary carrier functions (suspension stability, propellant performance) while eliminating environmental harm.
Solution Approach 2:
The patent converts the potential harm of requiring multiple actuations (which would increase device usage and waste) into a benefit by using HFO-1234ze(E) to enable stable single actuation delivery. The environmentally friendly carrier allows higher API concentrations without aggregation, making single actuation effective and reducing overall device disposal frequency.
3Stability of the object's composition
If the amount of API is reduced to prevent flocculation, then the suspension stability is improved, but the productivity deteriorates requiring multiple actuations
Solution Approach 1:
The HFO-1234ze(E) carrier acts as an intermediary that enables higher API concentrations by preventing direct particle-particle interactions. The carrier molecules surround and stabilize API particles, allowing them to remain dispersed at higher concentrations without flocculation, thus enabling single actuation delivery of full dosage.
4Productivity
If the propellant vapor pressure is increased to improve atomization, then the delivery performance is improved, but the toxicity increases
Solution Approach 1:
The patent changes the propellant parameters by selecting HFO-1234ze(E) which has optimized vapor pressure and boiling point characteristics. This parameter change achieves effective atomization for single actuation delivery while maintaining low toxicity and high chemical stability, unlike conventional high vapor pressure propellants.
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 described compositions achieve stable suspension of fluticasone, allowing for single actuation to deliver the desired dose with high stability and low environmental impact.
Implementation Method 1
a carrier in which said fine particles of fluticasone are suspended, said carrier comprising: (i) from greater than 95% by weight to less than 99.5% by weight of HFO-1234ze(E)
Implementation Method 2
The use of HFO-1234ze(E) as a carrier with ethanol and optionally polyethylene glycol (PEG) to suspend fluticasone particles, with specific weight percentages to prevent flocculation
Implementation Method 3
These include an appropriate boiling point and vapor pressure so that it can be liquefied in a closed container at room temperature but develop a high enough pressure when the pMDI is activated to deliver the drug as an atomized formulation
Data Source
AI summary
Disclosed are medicinal compositions, and devices, methods and systems which use same, comprising a carrier and at least one medicinally active compound, said carrier comprising at least 1234ze(E) and ethanol.