Co-Suspension Compositions for MDI Particle Dispersion Stability
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Solution Overview
Problem
Metered dose inhalers (MDIs) face challenges with the aggregation and flocculation of fine active agent particles, leading to mechanical failures, inconsistent dose delivery, and decreased aerosol performance due to the use of non-CFC propellants like HFA and PFC, which require new stabilization methods to maintain particle dispersion and aerosol properties over time.
Innovation Solution
The development of co-suspension compositions that include active agent particles and suspending particles, where the active agent particles associate with the suspending particles to form a stable dispersion within the propellant medium, preventing separation and maintaining aerosol performance and dose uniformity, even under temperature cycling and storage conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If non-CFC propellants (HFA and PFC) are used to replace CFCs, then environmental impact is reduced, but fine active agent particles aggregate and flocculate more rapidly
Solution Approach 1:
The patent introduces a surfactant as an intermediary substance that mediates between the non-CFC propellant and the fine active agent particles. The surfactant adsorbs at the interface between the propellant and particles, reducing surface tension and preventing particle aggregation and flocculation, thereby maintaining stable dispersion in environmentally-friendly propellant systems.
Solution Approach 2:
The patent creates a composite propellant system combining non-CFC propellants (HFA and/or PFC) with surfactants. This composite formulation leverages the environmental benefits of non-CFC propellants while the surfactant component provides stabilization, preventing particle aggregation and maintaining aerosol performance.
2Productivity
If fine active agent particles are used to improve aerosolization, then aerosol performance is enhanced, but mechanical failures occur due to valve orifice obstruction
Solution Approach 1:
The surfactant acts as a protective intermediary that coats the fine active agent particles, preventing them from aggregating into larger clumps that could obstruct the valve orifice. This maintains the fine particle size necessary for effective aerosolization while eliminating the mechanical failure risk.
Solution Approach 2:
The surfactant is incorporated into the formulation in advance to preemptively prevent particle aggregation and flocculation before they can occur during storage or use. This preliminary protective action ensures particles remain dispersed and do not form obstructions in the valve mechanism.
3Productivity
If fine active agent particles are suspended in propellant, then aerosol delivery is achieved, but rapid sedimentation and creaming occur leading to inconsistent dose delivery
Solution Approach 1:
The surfactant serves as a stabilizing intermediary that prevents rapid sedimentation and creaming of fine active agent particles in the propellant suspension. By reducing interfacial tension and providing steric or electrostatic repulsion, the surfactant maintains uniform particle distribution, ensuring consistent dose delivery throughout the product shelf life.
4Productivity
If active agent is micronized to improve aerosol properties, then fine particle fraction increases, but aggregation and flocculation occur rapidly
Solution Approach 1:
The surfactant is introduced as a protective intermediary that adsorbs onto the surface of micronized active agent particles, preventing them from aggregating and flocculating. This allows the formulation to maintain the high fine particle fraction necessary for effective pulmonary delivery while preventing the rapid aggregation that normally occurs with micronized particles.
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 co-suspension compositions achieve stable aerosol performance and consistent delivered dose uniformity, maintaining a high fine particle fraction and mass median aerodynamic diameter, even with potent and highly potent active agents, and are effective in treating respiratory diseases such as asthma and COPD without the need for additional stabilizing agents.
Implementation Method 1
MDIs use a relatively high vapor pressure propellant to expel aerosolized droplets containing an active agent into the respiratory tract when the MDI is activated
Implementation Method 2
Fine particles of active agent suspended in a propellant or propellant system tend to aggregate or flocculate rapidly
Implementation Method 3
Fine particles of active agent suspended in a propellant or propellant system tend to aggregate or flocculate rapidly
Implementation Method 4
surfactants are often used to coat the surfaces of the active agent in order to minimize or prevent the problem of aggregation and maintain a substantially uniform dispersion
Data Source
AI summary
Compositions, methods and systems are provided for pulmonary or nasal delivery of active agents via a metered dose inhaler. In one embodiment, the compositions include a suspension medium, active agent particles, and suspending particles, in which the active agent particles and suspending particles form a co-suspension within the suspension medium.