Protein Microparticle Production via Atomization and Solvent Dehydration

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Solution Overview

Problem

Traditional methods for producing protein microparticles, such as spray drying and freeze drying, often result in significant biological activity loss due to thermal, interfacial, and shear stresses, and require the addition of excess stabilizing excipients, leading to low microparticle density and potential off-target effects.

Innovation Solution

A process combining atomization with solvent-assisted dehydration, where protein solutions are atomized into liquid droplets that are then collected in a mixed dehydration solvent, allowing for the generation of biologically active protein microparticles with controlled size and high protein content without the need for excessive excipients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional spray drying or freeze drying methods are used to produce protein microparticles, then microparticles can be obtained, but significant biological activity loss occurs due to thermal, interfacial, and shear stresses

Engineering Contradiction:
Improvebiological activityVSAvoidthermal, interfacial, and shear stresses
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the processing parameters from high-temperature spray drying or freeze drying to ambient temperature processing. The protein solution is atomized into fine droplets and dried at ambient temperature, eliminating thermal stress while maintaining microparticle formation capability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces the mechanical stress-intensive traditional drying systems with an atomization-based system. By converting the protein solution into fine aerosol droplets, the surface area increases dramatically, enabling rapid ambient drying without requiring high mechanical energy input that causes shear stress.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If excess stabilizing excipients are added to mitigate processing stress, then biological activity is preserved, but microparticle biological density decreases and off-target effects increase

Engineering Contradiction:
Improvebiological activityVSAvoidmicroparticle biological density
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The invention extracts and eliminates the need for excess stabilizing excipients by using ambient temperature atomization drying. The gentle processing conditions inherently preserve biological activity without requiring additional stabilizing agents, thus maintaining high protein content and biological density in the microparticles.

Inventive Principle:
Principle #2Taking out (Extraction)

3Manufacturing precision

If traditional methods are used to produce microparticles, then processing can be performed, but control over particle design features (size, dispersity, morphology, density) is limited

Engineering Contradiction:
Improveparticle design feature controlVSAvoidprocess simplicity
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The invention utilizes atomization technology where particle size, dispersity, and morphology can be precisely controlled by adjusting atomization parameters such as gas pressure, flow rate, and nozzle design. This provides excellent manufacturing precision while maintaining relatively simple process operation.

Inventive Principle:
Principle #35Parameter changes

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 method effectively retains at least 90% of the protein's original specific activity and achieves high protein loading, with at least 85% of microparticles having a diameter of 30 µm or less, and contains at least 75% protein by weight, while minimizing processing stresses and excipient use.

Implementation Method 1

A protein solution containing a protein and a liquid is atomized to form liquid droplets

Methodology Applied
Scientific EffectUltrasonic vibration: Ultrasonic Vibration

Implementation Method 2

The droplets are then collected in a mixed dehydration solvent to generate the protein microparticles

Methodology Applied
Scientific EffectSolvent-assisted dehydration: Absorption (physical)

Data Source

PatentEP2773330B1Processes for producing protein microparticles
Publication Date: 2020.09.30 BATTELLE MEMORIAL INST
  • EP2773330B1 patent drawingFigure 1
  • EP2773330B1 patent drawingFigure 2
  • EP2773330B1 patent drawingFigure 3

AI summary

Processes and apparatuses for producing biologically-active, protein-rich microparticles under ambient conditions are disclosed. A protein solution is atomized and collected in a dehydration solvent that is being mixed. The resulting protein microparticles retain high specific activity without the need for large amounts of stabilizing excipients.