Beta2-agonist Microparticles Coated with Fatty Acid
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Solution Overview
Problem
Beta2-agonists used in inhalable formulations face challenges with chemical stability, physical stability, and adhesion issues, leading to undesirable particle growth, aggregation, and reduced effectiveness in respiratory treatments.
Innovation Solution
Crystalline microparticles coated with a C12-C20 fatty acid, prepared by dissolving the fatty acid in a fluorinated propellant and mixing with micronized beta2-agonist, followed by spray-drying to achieve a uniform and stable coating, enhancing chemical and physical stability and reducing adhesion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If beta2-agonists are formulated in HFA propellant, then the drug can be administered by inhalation, but the drug absorbs into rubber valve components causing seizure and reduced fine particle mass
Solution Approach 1:
A surfactant coating is applied to the beta2-agonist particles to act as an intermediary layer between the drug and the rubber valve components. This coating prevents direct contact and absorption of the drug into the rubber, thereby preventing valve seizure while maintaining inhalation administration functionality.
Solution Approach 2:
The surface properties of the beta2-agonist particles are modified by coating with surfactant, changing parameters such as surface charge, hydrophobicity, and adhesion characteristics. This parameter change reduces the affinity between the drug particles and rubber components, preventing absorption and valve seizure.
2Adaptability or versatility
If beta2-agonists are suspended in HFA propellant, then inhalable formulation is achieved, but partial solubility causes particle size increase and aggregation during storage
Solution Approach 1:
Surfactant coating acts as a steric barrier between the beta2-agonist particles and the HFA propellant, reducing the extent of drug-propellant interaction. This intermediary layer minimizes partial solubility effects, preventing particle growth and aggregation during storage while maintaining suspension stability for inhalation.
3Ease of manufacture
If surfactant is dissolved in solvent for coating particles, then coating can be applied, but uniform coating is difficult to achieve due to unpredictable precipitation
Solution Approach 1:
The solvent system parameters are optimized to control surfactant precipitation behavior. By adjusting solvent composition, temperature, and evaporation rate parameters, the precipitation process is made more predictable and controlled, enabling uniform surfactant coating on beta2-agonist particles during the manufacturing process.
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 coated microparticles exhibit improved chemical stability, slow sedimentation, reduced adhesion, and increased respirable fraction, ensuring effective delivery and prolonged therapeutic efficacy in respiratory treatments.
Implementation Method 1
isolating particles of surfactant coated active agent either by filtration and drying, or by removal of the solvent by evaporation
Implementation Method 2
the particles obtained in this way are prevalently amorphous. However, it is known that amorphous or prevalently amorphous materials tend to absorb water in larger amounts than crystalline ones
Data Source
AI summary
Crystalline microparticles consisting of a phenylalkylamino beta2-adrenergic agonist coated with a C12-C20 fatty acid are useful for the preparation of pharmaceutical aerosol formulations in form of suspension in a liquefied propellant gas or powder formulations.