Fluticasone MDI Composition for Stable Dosing and Accurate Dose Count
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Solution Overview
Problem
Existing metered dose inhalers (MDIs) face issues with stability and variability in drug delivery due to Ostwald ripening and particle aggregation, leading to inconsistent dosing and potential under/over counting without a dose counter, posing risks during asthma attacks.
Innovation Solution
A stable pharmaceutical composition of fluticasone or its ester, using HFA 227 and HFA 134a propellants, with a canister, metering valve, actuator, and dose counter, where the dose counter is not directly attached to the canister, and the canister is coated with fluorocarbon polymers to prevent adhesion, ensuring consistent dosing and accurate count.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If fluticasone is formulated as a microcrystalline suspension in HFA-134a, then the drug can be delivered via MDI, but Ostwald ripening and particle aggregation occur leading to particle size growth and dosing variability
Solution Approach 1:
The patent changes the physical-chemical parameters of the formulation by using fluticasone hemifumarate salt instead of free base fluticasone, and by controlling crystallization conditions to produce microcrystalline particles with specific size distribution (D10: 0.5-2.0 μm, D50: 2.0-4.0 μm, D90: 4.0-6.0 μm). This parameter change prevents Ostwald ripening and maintains particle size stability throughout the shelf life of the product.
Solution Approach 2:
The patent creates a composite formulation system consisting of fluticasone hemifumarate microcrystals dispersed in HFA-134a propellant, with specific attention to the interface between solid drug particles and liquid propellant. The composite nature of this suspension system, with controlled particle morphology and size distribution, prevents aggregation and maintains dosing consistency.
2Loss of information
If a dose counter is added to track remaining doses, then patients can monitor medication usage, but the dose counter may interfere with aerosol flow or cause counting errors
Solution Approach 1:
The patent segments the MDI system into distinct functional components: the canister containing the pharmaceutical composition, the valve mechanism for metering, the actuator for aerosol generation, and the dose counter for tracking. This segmentation allows the dose counter to be positioned and designed independently to avoid interfering with aerosol flow while maintaining accurate counting functionality.
Solution Approach 2:
The patent introduces an intermediary mechanism between the actuation system and the counting system, where the dose counter tracks doses through a mechanical or electronic interface that does not obstruct the aerosol flow path. This intermediary approach allows independent optimization of both dosing accuracy and flow performance.
3Quantity of substance
If drug particles adhere to canister or valve surfaces, then deposition occurs reducing delivered dose, but preventing adhesion requires special surface treatments
Solution Approach 1:
The patent changes the surface energy parameters of the canister and valve surfaces through fluorocarbon polymer coating, creating a low-adhesion surface that prevents drug particle adhesion. This parameter change in surface chemistry reduces drug deposition and ensures consistent dosing without requiring complex mechanical modifications.
Solution Approach 2:
The fluorocarbon polymer coating acts as an intermediary layer between the drug particles and the canister/valve surfaces. This intermediary coating prevents direct interaction and adhesion between drug particles and metal surfaces, reducing deposition and improving dose consistency.
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 solution provides a stable MDI with consistent drug delivery, accurate dose counting, and reduced side effects by maintaining particle size and preventing adhesion, enhancing patient safety and treatment efficacy.
Implementation Method 1
the canister is coated with fluorocarbon polymers to prevent adhesion
Implementation Method 2
a stable pharmaceutical composition of fluticasone or its ester, using HFA 227 and HFA 134a propellants
Data Source
AI summary
The invention relates to metered dose inhaler comprising a stable pharmaceutical composition of fluticasone or its pharmaceutically acceptable ester contained in a canister fitted with a metering valve, an actuator and dose counter. The invention also relates to a process for preparing said pharmaceutical composition and its use in the treatment of respiratory disorders such as asthma in a subject (e.g., a human).