Ultrasonic Crystallization for Controlled Particle Size
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods for producing small crystals, such as those used in pharmaceutical and agro-chemical industries, often result in particles that are too small or of inappropriate shape, leading to undesirable surface transformations and flow-rate issues, particularly when using milling processes, and lack direct crystallization from solution.
Innovation Solution
A process involving the contact of a solute in a solvent with an anti-solvent in a ratio higher than 20:1, under ultrasonic irradiation, to produce crystals of desired size up to 10 μm, with the anti-solvent stream being re-circulated and potentially containing additional solute, allowing for controlled crystal formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If milling processes are used to make small particles, then particle size can be reduced, but the material properties are deteriorated and particles become unsuitable for desired use
Solution Approach 1:
The patent replaces mechanical milling processes with a solution-based crystallization process. Instead of mechanically grinding materials to achieve small particle sizes, the invention uses controlled crystallization from solution to form crystals of desired size, thereby avoiding the detrimental effects of mechanical processing on material properties.
Solution Approach 2:
The patent employs parameter changes by controlling crystallization conditions such as temperature, solvent composition, and anti-solvent addition rate to produce crystals of specific size ranges (500 nm to 10 μm). This allows precise control over particle size while maintaining intact material properties.
2Length of moving object
If milling processes are used to make small particles, then particle size can be reduced, but particles undergo morphological alterations and surface polymorphological transformation
Solution Approach 1:
The patent substitutes mechanical milling with chemical crystallization processes. By forming crystals through controlled precipitation and crystallization from solution, the method avoids mechanical stress and shear forces that cause morphological alterations and surface polymorphological transformation during milling.
Solution Approach 2:
The patent performs preliminary actions by pre-dissolving the active principle in a suitable solvent to form a saturated or near-saturated solution before adding anti-solvent. This controlled preliminary dissolution step ensures that crystallization occurs under uniform conditions, producing morphologically intact crystals without the damaging mechanical action of milling.
3Length of moving object
If milling processes are used to make small particles, then particle size can be reduced, but particles become highly charged which undermines flow-rates
Solution Approach 1:
The patent replaces mechanical size reduction with controlled crystallization. The resulting crystals have inherent surface properties that do not become highly charged during processing, thereby maintaining good flow characteristics and avoiding the flow-rate undermining issue associated with milled particles.
4Manufacturing precision
If conventional anti-solvent mixing ratios are used (up to 10:1), then crystallization can be achieved, but crystals do not reach desired size range
Solution Approach 1:
The patent applies parameter changes by extending the anti-solvent to solvent flow rate ratio beyond the conventional 10:1 limit to achieve higher ratios (up to 100:1 or more). This parameter adjustment enables precise control over crystal size, producing crystals in the desired 500 nm to 10 μm range while maintaining high productivity.
Solution Approach 2:
The patent employs excessive action by using anti-solvent flow rates that far exceed the conventional minimum required for crystallization. This excessive anti-solvent addition (ratios up to 100:1) ensures complete precipitation and controlled crystal growth, achieving both precise size control and high crystal yield simultaneously.
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 enables the production of crystals with a mean diameter ranging from 500 nm to 10 μm, suitable for various active pharmaceutical and agro-chemical agents, improving particle stability and flow properties while avoiding morphological alterations.
Implementation Method 1
contacting at least one solute in a solvent in a first flowing stream with an anti-solvent in a second flowing stream wherein the flow rate ratio of the anti-solvent: solvent is higher than 20:1, and collecting crystals that are generated
Implementation Method 2
The control of crystal and precipitate particle size is very important in some circumstances, in particular in the pharmaceutical and agro-chemical industries in which the final product form of the active principal of interest is in the form of a fine powder
Implementation Method 3
The term 'anti-solvent' means a fluid which promotes precipitation from the solvent of the active principal of interest
Implementation Method 4
The anti-solvent may comprise a cold gas, or a fluid which promotes the precipitation via a chemical reaction, or which decreases the solubility of the active principal of interest in the solvent
Data Source
AI summary
A process for preparing crystalline particles of an active principal in the presence of ultrasonic irradiation that comprises contacting a solution of a solute in a solvent in a first flowing stream with an anti-solvent in a second flowing stream causing the mixing thereof, wherein the flow rate ratio of the anti-solvent: solvent is higher than 20:1, and collecting crystals that are generated.