Fluid-Jet Mill Recirculation for Drug Amorphization
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Solution Overview
Problem
Current drug/carrier co-grinding processes using air jet mills do not achieve the high-energy activation levels necessary for molecular dispersion and inclusion of drugs into carriers, leading to suboptimal biopharmaceutical properties in poorly soluble drugs.
Innovation Solution
Modifying fluid-jet mills to allow extended residence time of the drug/carrier mixture within the grinding chamber, utilizing a recirculation pipe to maintain the mixture under shock action from expanding fluid, achieving mechanochemical activation comparable to high-energy mills like ball or vibration mills.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional air jet mills are used for drug/carrier co-grinding, then the process is simple and contamination is minimized, but high-energy activation levels necessary for molecular dispersion and inclusion are not achieved
Solution Approach 1:
The fluid-jet mill is pre-configured with specific nozzle arrangements and recirculation pathways to ensure that drug and carrier particles are continuously exposed to high-energy fluid shocks before the actual grinding process begins, pre-conditioning the particles for effective molecular dispersion and inclusion
Solution Approach 2:
A recirculation system is implemented where ground particles are continuously circulated back through the grinding chamber multiple times, ensuring continuous exposure to high-energy fluid shocks and maintaining sustained activation energy levels throughout the processing period
2Manufacturing precision
If extended residence time is implemented in fluid-jet mills, then mechanochemical activation is achieved, but process complexity and equipment modification requirements increase
Solution Approach 1:
The system utilizes pneumatic recirculation pathways where pressurized gas flows carry particles through circulation loops, using fluid dynamics rather than mechanical means to achieve extended residence time and high-energy activation without complex mechanical modifications
Solution Approach 2:
The process optimizes parameters such as fluid pressure, nozzle geometry, and circulation rate to achieve the desired extended residence time and activation effects, adjusting operational parameters rather than fundamentally redesigning the equipment structure
3Manufacturing precision
If high-energy mills like ball or vibration mills are used, then mechanochemical activation is achieved, but contamination with media material and grinding chamber lining material occurs
Solution Approach 1:
The patent replaces mechanical grinding systems (ball mills, vibration mills) with a fluid-jet-based system where high-velocity fluid shocks provide the necessary activation energy without physical contact between grinding media and particles, eliminating contamination from media and lining materials
Solution Approach 2:
A fluid medium (gas or liquid) serves as an intermediary that transfers energy to the drug and carrier particles through shock waves and turbulence, mediating the activation process without direct mechanical contact that would cause contamination
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 approach results in significantly improved chemico-physical and biopharmaceutical characteristics, including high amorphization, nanocrystallinity, and enhanced solubilization kinetics of drugs, while preventing contamination and increasing co-grinding yield, thus producing better-quality drug/carrier composites.
Implementation Method 1
maintain the mixture under shock action from expanding fluid
Implementation Method 2
achieve mechanochemical activation comparable to high-energy mills like ball or vibration mills
Implementation Method 3
fluid-jet mills suitably modified to convert the co-grinding process into mechanochemical activation
Implementation Method 4
a high percentage of amorphous phase, nanocrystallinity
Implementation Method 5
preparation by a high-energy co-grinding process using fluid-jet mills
Data Source
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AI summary
Disclosed is a process for the preparation of drug/carrier inclusion composites which involves co-grinding the mixture of drug and carrier powders in a fluid-jet mill, in particular one using air or nitrogen as the fluid, which is suitably modified to allow mechanical fusion of the powders.