Fluidized Bed Dry Milling for Nanoparticle Bioavailability
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Solution Overview
Problem
Current methods for producing finely divided drug particles are limited by the inability to achieve high volume fractions of biologically active materials, leading to poor bioavailability and slow absorption due to particle size constraints and contamination issues in wet milling processes.
Innovation Solution
A dry milling process that produces particles of biologically active materials with increased surface area at volume fractions above 25 v/v %, with average particle sizes ranging from 25 nm to 2000 nm, maintaining crystallinity and avoiding significant amorphous content, using a mill with milling bodies and a grinding matrix.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If wet grinding is employed to reduce particle size, then particle size is reduced to approximately 10 microns, but contamination occurs and flocculation restricts further size reduction
Solution Approach 1:
The patent replaces wet mechanical grinding with a fluidized bed process that uses fluid dynamics and heat transfer to achieve particle size reduction and amorphous conversion without mechanical contact, thereby eliminating contamination and flocculation issues
Solution Approach 2:
The patent utilizes phase transition by converting particles from crystalline to amorphous state through rapid heating and cooling in the fluidized bed, achieving size reduction and solubility improvement without mechanical forces that cause contamination
2Length of moving object
If conventional dry milling is used to reduce particle size, then particle size reaches about 100 microns, but material cakes on the milling chamber preventing further diminution
Solution Approach 1:
The patent replaces mechanical dry milling with a fluidized bed process that uses fluid flow to suspend and treat particles, eliminating the caking problem that occurs when material adheres to mechanical milling chamber surfaces
Solution Approach 2:
The patent employs fluidized bed technology using gas or liquid flow to suspend particles in a fluid state, enabling continuous processing without the mechanical contact and caking issues inherent in conventional dry milling systems
3Length of moving object
If airjet milling is used to produce fine particles, then particle size ranges from 1 to 50 microns, but volume fraction of biologically active material remains limited
Solution Approach 1:
The patent changes the processing parameters by using fluidized bed conditions (fluid velocity, temperature, residence time) instead of mechanical impact parameters, enabling higher volume fractions of biologically active material to be processed into fine particles without agglomeration
4Reliability
If particle size is decreased to increase surface area and dissolution rate, then bioavailability improves, but manufacturing complexity increases due to process constraints
Solution Approach 1:
The patent replaces complex mechanical size reduction equipment with a simpler fluidized bed system that achieves particle size reduction and amorphous conversion through fluid dynamics and thermal processing, reducing manufacturing complexity
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 faster absorption and bioavailability of poorly soluble drugs, such as naproxen and metaxalone, by achieving smaller particle sizes and higher volume fractions, suitable for acute and chronic pain management, and applicable to various biologically active compounds.
Implementation Method 1
A dry milling process that produces particles of biologically active materials with increased surface area at volume fractions above 25 v/v %, with average particle sizes ranging from 25 nm to 2000 nm
Data Source
AI summary
The present invention relates to methods for producing particles of a biologically active material using dry milling processes as well as compositions comprising such materials, medicaments produced using said biologically active materials in particulate form and/or compositions, and to methods of treatment of an animal, including man, using a therapeutically effective amount of said biologically active materials administered by way of said medicaments.