Microparticle Formulation Cooling for Respiratory Delivery
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Solution Overview
Problem
There is a need for methods to produce microparticle formulations with uniform size distribution for targeted delivery of active agents to specific respiratory sites, while minimizing systemic exposure and ensuring stability against degradation from packaging materials.
Innovation Solution
The method involves mixing an active agent with a counterion and an organic solvent, followed by controlled cooling to a predetermined temperature at a constant rate, which allows for the formation of microparticles with a narrow size distribution, and incorporating scavenging agents to protect against degradation from packaging materials.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If microparticles with smaller MMAD (3-8 microns) are used to increase absorption into bloodstream, then systemic exposure increases, but this poses increased risk of unwanted systemic exposure
Solution Approach 1:
The patent applies parameter changes by precisely controlling the MMAD of microparticles within a specific range (3-8 microns) to optimize absorption while managing systemic exposure risk. This involves adjusting formulation parameters such as particle size distribution, composition, and physical properties to achieve the desired balance between therapeutic efficacy and safety
Solution Approach 2:
The patent employs partial action by delivering microparticles with controlled size distribution that achieves sufficient absorption for therapeutic effect without excessive penetration into systemic circulation. The MMAD control ensures that only the necessary fraction of particles is absorbed, avoiding over-exposure while maintaining treatment effectiveness
2Manufacturing precision
If microparticles are made small enough to deposit in upper and central respiratory airways, then target site delivery is achieved, but they may reach deeper parts of lungs and be absorbed into bloodstream
Solution Approach 1:
The patent utilizes parameter changes by establishing a specific MMAD range (3-8 microns) that optimizes deposition in upper and central respiratory airways while minimizing deep lung penetration. This precise parameter control ensures particles are small enough for target site delivery but large enough to avoid excessive systemic absorption
Solution Approach 2:
The patent implements feedback mechanisms through rigorous characterization and control of particle size distribution during manufacturing. By continuously monitoring and adjusting the MMAD and size distribution parameters, the process ensures consistent delivery to target sites while preventing unwanted deep lung deposition and systemic absorption
3Stability of the object's composition
If active agent is protected from packaging materials using scavenging agents, then stability is improved, but formulation complexity increases
Solution Approach 1:
The patent employs scavenging agents as intermediary substances that protect the active agent from degradation by packaging materials. These scavenging agents act as mediators between the active agent and potential harmful components in packaging, such as peroxides or aldehydes, preventing direct harmful interactions while maintaining formulation simplicity
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
This approach results in microparticles with precise size control for targeted respiratory delivery, reducing systemic absorption and maintaining stability, ensuring effective and safe administration of drugs like DAS181 for respiratory tract infections and disorders.
Implementation Method 1
cooling the feedstock solution at a constant rate to a predetermined temperature to form microparticles
Data Source
AI summary
Microparticle formulations of a sialidase fusion protein are produced by contacting an aqueous solution of a protein or other active agent with an organic solvent, a counterion and a scavenging agent, and chilling the solution. The microparticles are useful for preparing stable, uniform pharmaceuticals of predetermined defined dimensions.