Fine Particle Precipitation Apparatus with Segmented Collection
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Solution Overview
Problem
Current methods for producing uniform micron-sized particles of fragile molecules like proteins are inefficient, leading to unacceptable variation in particle size, aggregation, and low yield, particularly due to exposure to organic solvents and the limitations of existing dense gas techniques such as RESS and GAS processes.
Innovation Solution
An apparatus with separate precipitation and collection chambers, where the particles are conveyed from the precipitation chamber to a collection chamber with an inlet and outlet configuration that balances forces to prevent aggregation, using a neutral anti-solvent like ethane and a modifier like ethanol to produce fine particles with a narrow size distribution, and a dual-stage process to enhance collection efficiency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional dense gas techniques (RESS, GAS) are used to produce fine particles, then particle formation is achieved, but particle size variation is unacceptable and yield is low
Solution Approach 1:
The system is divided into two separate chambers: a precipitation chamber where particles are formed and a collection chamber where particles are gathered. This segmentation allows the particle formation process to be optimized independently from the collection process, enabling better control over particle size uniformity while improving overall yield by preventing particle loss during collection.
Solution Approach 2:
A neutral anti-solvent (ethane) modified with a modifier (ethanol) is used as an intermediary substance to facilitate controlled precipitation. The modifier alters the anti-solvent's properties to enable gradual, controlled particle formation, reducing size variation and improving yield by preventing premature aggregation.
2Quantity of substance
If organic solvents are used in gas anti-solvent processes, then particle precipitation is achieved, but biological activity is lost due to solvent exposure
Solution Approach 1:
The patent changes the chemical parameters of the anti-solvent system by using a neutral gas (ethane) instead of traditional organic solvents, and modifies it with a specific modifier (ethanol) in controlled amounts. This parameter change maintains the ability to induce precipitation while eliminating the harmful effect of organic solvent exposure on biological activity.
Solution Approach 2:
The use of ethane as the base anti-solvent creates an inert environment that does not chemically interact with or damage the biological molecules. The modified anti-solvent system provides a chemically neutral atmosphere during particle formation, preserving biological activity while still enabling effective precipitation.
3Device complexity
If particles are collected in a single chamber, then collection is simplified, but aggregation and compaction occur reducing fine particle quality
Solution Approach 1:
The collection system is segmented into a separate collection chamber distinct from the precipitation chamber. This segmentation allows particles to be collected in a dedicated environment where aggregation and compaction are minimized, while the simplicity of the overall system is maintained through straightforward chamber design and fluid flow paths.
4Speed
If high pressure and high flow-rate dense gas is used, then particle formation is rapid, but particles become compacted and aggregated
Solution Approach 1:
The patent modifies the anti-solvent parameters by introducing a modifier (ethanol) that changes the saturation and precipitation kinetics. This allows rapid particle formation to be achieved under controlled conditions without excessive pressure and flow-rate that would cause compaction and aggregation, maintaining particle stability.
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 increases the yield and recovery of fine particles, maintains biological activity, and produces particles with a higher mass fraction of less than 5 μm diameter, enabling more efficient and effective pulmonary delivery of pharmaceuticals.
Implementation Method 1
contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber
Implementation Method 2
contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber
Implementation Method 3
the outlet is disposed above the inlet in use of the apparatus, such that gravity exerts a force generally towards the inlet on particles adjacent the outlet
Implementation Method 4
inlet and outlet configuration that balances forces to prevent aggregation
Implementation Method 5
using a neutral anti-solvent like ethane and a modifier like ethanol to produce fine particles with a narrow size distribution
Data Source
AI summary
The invention provides an apparatus for forming fine particles of a substance in a precipitation chamber, in which the apparatus has means to convey the fine particles from the precipitation chamber to at least one particle collection chamber, downstream of the precipitation chamber, the particle collection chamber having an inlet and an outlet separate from the inlet. The invention also provides a method of forming fine particles of a substance, the method comprising contacting a non-gaseous fluid containing the substance with a dense fluid to expand the non-gaseous fluid in a precipitation chamber, conveying a resulting mixture of fluid and the fine particles from the precipitation chamber to a collection chamber, the collection chamber having an inlet and an outlet separate from the inlet.