Microparticle Formation Using Swirling Liquid CO2 Cooling

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Solution Overview

Problem

Existing processes for producing small, spherical microparticles face challenges such as the use of complex nozzle designs, supercritical fluids, high spraying temperatures, and inefficient water removal, leading to non-spherical particles with variable sizes and poor reproducibility.

Innovation Solution

A process involving a fluid mixture of lipids, lipid-polymer compounds, and polymers, mixed with a desiccating gas and/or plasticizing gas, ejected through a nozzle to create a capillary or preatomized flow, then contacted with an expanding liquid or dense CO2 swirling flow to form spherical microparticles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If supercritical fluids and high-speed rotating disc nozzles are used, then particle size can be reduced, but device complexity and operating conditions become excessively complex

Engineering Contradiction:
Improveparticle size controlVSAvoidnozzle design complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention changes the physical state parameter of CO2 from supercritical to liquid, simplifying the system while maintaining particle size control capability through liquid CO2 expansion and cooling effects

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention extracts and removes the high-speed rotating disc nozzle component, replacing it with a stationary nozzle system that achieves particle formation through liquid CO2 expansion rather than mechanical rotation

Inventive Principle:
Principle #2Taking out (Extraction)

2Productivity

If mixing with supercritical CO2 is performed in advance, then atomization efficiency improves, but temperature-sensitive substances are exposed to large amounts of heat causing damage

Engineering Contradiction:
Improveatomization efficiencyVSAvoidthermal damage to sensitive substances
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the temperature parameter by using liquid CO2 instead of supercritical CO2, enabling atomization at lower temperatures that do not damage temperature-sensitive substances

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention performs preliminary cooling by introducing liquid CO2 before the atomization process, ensuring temperature-sensitive substances are protected from thermal damage during the atomization step

Inventive Principle:
Principle #10Preliminary action

3Loss of energy

If external mixing at nozzle opening is used, then thermal separation occurs reducing efficiency, but particle size becomes larger and less reproducible

Engineering Contradiction:
Improvethermal energy efficiencyVSAvoidparticle size reproducibility
Core Design Contradiction:
Loss of energyVSManufacturing precision

Solution Approach 1:

The invention merges the mixing and atomization processes into a single integrated step within the nozzle, where liquid CO2 and substance mixture are mixed and atomized simultaneously, eliminating thermal separation and improving particle size reproducibility

Inventive Principle:
Principle #5Merging (Combining)

4Temperature

If two-component nozzle arrangement is used, then cooling can be achieved, but thermal coupling is inadequate and cooling optimization becomes difficult

Engineering Contradiction:
Improvecooling capabilityVSAvoidnozzle arrangement complexity
Core Design Contradiction:
TemperatureVSDevice complexity

Solution Approach 1:

The invention combines the cooling function directly into the atomization nozzle by introducing liquid CO2 at the nozzle opening, merging cooling and atomization into a single component rather than using separate two-component nozzle arrangements

Inventive Principle:
Principle #5Merging (Combining)

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 process produces spherical microparticles with a narrow size distribution and improved water removal efficiency at low temperatures, using relatively low-cost equipment and scalable to various scales without requiring supercritical conditions.

Implementation Method 1

contacting the capillary or preatomized flow obtained in step c) with an expanding liquid or dense CO2 swirling or spiraling flow to obtain the solid microparticles

Methodology Applied
Scientific EffectJoule-Thomson effect: Joule-Thomson Effect

Implementation Method 2

mixing the fluid mixture of step a) with a desiccating gas and/or plasticizing gas

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Data Source

PatentEP4440732B1Process and apparatus for the manufacture of solid microparticles
Publication Date: 2026.02.04 SITEC PHARMABIO SL
  • EP4440732B1 patent drawingFigure 1~2
  • EP4440732B1 patent drawingFigure 3~4
  • EP4440732B1 patent drawingFigure 5~6

AI summary

The present invention relates to a process for the manufacture of solid microparticles comprising: a) providing a fluid mixture comprising one or more molecules of interest, one or more compounds selected from the group consisting of lipids, lipid-polymer compounds and polymers, and optionally water, b) mixing the fluid mixture of step a) with a desiccating gas and/or plasticizing gas to provide a dispersion of the fluid mixture of step a) and the desiccating gas and/or plasticizing gas, c) ejecting the dispersion obtained in step b) through a nozzle thereby creating a capillary or preatomized flow, and d) contacting the capillary or preatomized flow obtained in step c) with an expanding liquid or dense CO2 swirling or spiraling flow to obtain the solid microparticles. The present invention also relates to an apparatus for carrying out the process of the invention.