Isoxazoline Crystallization for Large Particle Size Control
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Solution Overview
Problem
Existing methods do not effectively control the particle size of isoxazoline compound crystals, leading to inconsistent quality and performance in pharmaceutical applications.
Innovation Solution
A process involving controlled crystallization techniques, including temperature management, seed addition, and solvent recycling, to produce isoxazoline compound particles with defined dimensions and mechanical resilience.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional crystallization is used without control, then the process is simple, but the particle size cannot be controlled and bioavailability is compromised
Solution Approach 1:
The patent applies parameter changes by systematically controlling temperature, supersaturation level, and cooling rate during crystallization. By adjusting these parameters, the process achieves precise control over particle size (75-120 μm) while maintaining a manageable process complexity through defined operational ranges.
Solution Approach 2:
The patent implements feedback control by monitoring supersaturation levels and adjusting cooling rates accordingly. The process uses real-time measurement of crystal formation and adjusts operational parameters to maintain target particle size distribution, ensuring consistent bioavailability and efficacy.
2Productivity
If fast cooling rate is used, then crystal formation is rapid, but only tiny crystals are formed reducing bioavailability
Solution Approach 1:
The patent applies periodic action through controlled cooling phases followed by holding periods at specific temperatures. The process cycles between cooling to induce nucleation, holding to allow crystal growth, and re-cooling to achieve target size distribution. This periodic approach produces particles of desired size (75-120 μm) while maintaining efficient production rates.
Solution Approach 2:
The patent uses preliminary action by pre-cooling the solution to a temperature below the melting point before initiating crystal growth. This preliminary cooling creates the necessary supersaturation state that enables controlled crystal formation, ensuring particles achieve target size while maintaining rapid overall production.
3Manufacturing precision
If slow cooling rate is used, then large crystals are formed improving bioavailability, but the process time increases
Solution Approach 1:
The patent resolves this contradiction through periodic action by implementing alternating cooling and holding phases. The process cools rapidly to induce nucleation, then holds at specific temperatures to allow crystal growth to target size, and cycles this pattern. This achieves large particles (75-120 μm) with improved bioavailability while controlling total process time through efficient phasing.
Solution Approach 2:
The patent applies parameter changes by dynamically adjusting cooling rates and holding temperatures based on real-time crystal growth monitoring. The process transitions from rapid cooling for nucleation to slower cooling for growth, optimizing both particle size and process time through controlled parameter variation rather than constant slow cooling.
4Manufacturing precision
If no seed crystals are used, then the process is simpler, but particle size distribution is uncontrolled and efficacy is reduced
Solution Approach 1:
The patent applies preliminary action by pre-preparing and adding seed crystals to the solution before initiating the crystallization process. These seed crystals provide a controlled nucleation base that directs subsequent crystal growth to produce uniform particles of target size (75-120 μm). This preliminary step ensures precise particle size distribution and optimal efficacy while adding minimal process complexity through standardized seed addition protocols.
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
Produces isoxazoline compound particles with desired size distribution and thickness, enhancing bioavailability, efficacy, and safety profiles in pharmaceutical compositions.
Implementation Method 1
When a solid substance (solute) is mixed with a liquid solvent and stirred, the solute dissolves in the solvent to form a solution
Implementation Method 2
When the heated saturated solution is cooled, some of the dissolved solute comes out of the solution and crystals of solute start to form
Implementation Method 3
Cooling further we obtain a labile solution at point B where spontaneous formation of new crystals, i.e. nucleation, takes place
Data Source
AI summary
An improved process to produce large isoxazoline compound particles which comprises initiating crystallization and then maintaining the temperature of the crystallization in the metastable region by removing, reheating and recycling a portion of the solvent thereby allowing the existing crystals to grow larger while minimizing the formation of newer smaller crystals.