Controlled Crystallization Device for Narrow Crystal Size Distribution
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Solution Overview
Problem
Conventional crystallization techniques are inadequate for producing crystals of proper structure and size distribution, particularly for small sizes, in industries like pharmaceuticals, where controlled crystallization processes are crucial for bioavailability and stability.
Innovation Solution
The development of devices and methods that facilitate controlled crystal nucleation and growth through secondary nucleation processes, using a nucleation device to generate small crystals with a narrow size distribution by controlling parameters such as supersaturation, residence time, and mechanical forces, followed by crystal growth in a crystallizer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional antisolvent crystallization systems utilize rapid mixing of solution and antisolvent, then nucleation is triggered, but local regions of uncontrolled supersaturation are created leading to poor crystal size distribution
Solution Approach 1:
The crystallization process is divided into two separate chambers: a nucleation chamber where crystals are formed under controlled conditions, and a growth chamber where crystals mature. This segmentation allows independent optimization of nucleation and growth processes, preventing the uncontrolled supersaturation regions that occur in traditional single-chamber rapid mixing systems.
Solution Approach 2:
A controlled interface or transfer mechanism between the nucleation and growth chambers acts as an intermediary, allowing crystals to move from the nucleation zone to the growth zone in a controlled manner. This intermediary structure prevents direct rapid mixing while maintaining the nucleation trigger, thereby controlling supersaturation distribution.
2Productivity
If high supersaturation is used to trigger nucleation in traditional systems, then crystal formation is initiated, but control over crystal size and uniformity is lost
Solution Approach 1:
Different supersaturation levels are maintained in different chambers: high supersaturation is localized in the nucleation chamber to trigger nucleation, while the growth chamber maintains lower, controlled supersaturation levels to ensure uniform crystal growth. This local differentiation of quality parameters allows both nucleation initiation and size uniformity to be achieved.
Solution Approach 2:
The system controls the transition of supersaturation parameters as crystals move from the nucleation chamber to the growth chamber. By changing the supersaturation level parameter between chambers, the system initiates nucleation with high supersaturation then transitions to controlled growth conditions, achieving both nucleation and uniformity.
3Device complexity
If crystals are produced without decoupling nucleation and growth, then the process is simpler, but additional post-processing such as milling is required to achieve uniform size distribution
Solution Approach 1:
The crystallization process is segmented into distinct nucleation and growth chambers, allowing each process to be optimized independently. This segmentation enables crystals to achieve uniform size distribution during the crystallization process itself, eliminating the need for post-processing milling operations despite the increased device complexity.
4Productivity
If conventional crystallization techniques are used, then crystal production is achieved, but crystals of proper structure and narrow size distribution particularly for small sizes are not obtained
Solution Approach 1:
The system employs controlled changes in multiple parameters including supersaturation level, residence time, and temperature between the nucleation and growth chambers. These parameter changes enable precise control over crystal nucleation and growth, producing crystals with proper structure and narrow size distribution that cannot be achieved with conventional single-stage techniques.
Solution Approach 2:
The system dynamically controls the transition of crystals between nucleation and growth phases by adjusting operating parameters in real-time. This dynamic control allows the system to adapt to different crystal size targets and maintain narrow size distribution throughout the crystallization process, producing small crystals with precise structural control.
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
Enables the production of uniformly sized crystals without additional post-processing, such as milling, by decoupling nucleation and growth events, allowing for precise control over crystal characteristics and size distribution.
Implementation Method 1
producing crystals by inducing contact nucleation of a parent crystal
Implementation Method 2
a secondary nucleation process comprises: combining a supersaturated solution with a parent crystal in a nucleation chamber
Implementation Method 3
the concentration of the constituents in the supersaturated solution remains within the metastable zone width of the constituents
Implementation Method 4
applying a mechanical force to the parent crystal while the supersaturated solution is exposed to a parent crystal
Implementation Method 5
the mechanical force is a fluid shear force, an impact force or a frictional force
Data Source
AI summary
The invention in some aspects relates to devices and methods for nucleating crystals under controlled conditions. In some aspects of the invention, devices and methods are provided for continuous crystallization.