Dry-Milled Encapsulated Nanoparticles for Scalable Bioavailability
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Solution Overview
Problem
Existing methods for producing biologically active materials face challenges in achieving small particle sizes suitable for improved bioavailability, particularly for poorly soluble compounds, and are often not scalable to commercial levels, leading to issues with absorption and safety in therapeutic applications.
Innovation Solution
A dry milling process using a mill with milling bodies to produce biologically active material particles with sizes equal to or less than 2000 nm, maintaining crystallinity, and allowing for commercial scale production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of moving object
If conventional dry milling is used to reduce particle size, then particle size decreases, but material cakes on the milling chamber preventing further size reduction
Solution Approach 1:
The patent removes the biologically active material from the milling chamber periodically to prevent caking. The material is extracted, allowed to settle, and only the supernatant containing fine particles is retained for further processing, thereby preventing accumulation and caking in the chamber
Solution Approach 2:
The patent performs partial milling cycles where the material is milled for a specific time, then removed and settled. This partial action prevents over-milling and caking while still achieving the desired particle size reduction through multiple iterative cycles
2Length of moving object
If wet grinding is used to reduce particle size below 100 microns, then particle size decreases, but flocculation restricts further size reduction
Solution Approach 1:
The patent replaces wet grinding with a dry milling approach followed by liquid suspension and filtration. Instead of using liquid medium during milling (which causes flocculation), the process uses dry mechanical energy followed by wet separation, eliminating the flocculation problem while achieving fine particle sizes
Solution Approach 2:
The patent introduces a liquid suspension medium as an intermediary step between dry milling and final product formation. The milled powder is suspended in liquid, allowing fine particles to be separated by filtration without direct contact between particles that would cause flocculation
3Length of moving object
If commercial airjet milling is used, then particle size reaches 1-50 microns, but the process is not scalable to commercial production levels
Solution Approach 1:
The patent divides the milling process into multiple discrete stages with intermediate removal and settling steps. This segmentation allows the process to be scaled by increasing the number of cycles or parallel units rather than requiring a single large-scale jet mill, making it adaptable to commercial production volumes
Solution Approach 2:
The patent uses a conventional ball mill that can operate at both laboratory and commercial scales. The same basic equipment type serves multiple production levels by adjusting operational parameters and cycle numbers, eliminating the need for specialized small-scale jet milling equipment
4Speed
If particle size is reduced to increase surface area, then dissolution rate improves, but bioavailability may decrease due to capillary blockage
Solution Approach 1:
The patent optimizes the particle size parameter to a specific range (0.1-10 microns) that balances dissolution rate improvement with safety considerations. This parameter optimization ensures particles are fine enough to enhance dissolution but not so fine as to cause capillary blockage in intravenous applications
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
The method achieves fine particle sizes with enhanced surface area, improving bioavailability and absorption rates, enabling faster therapeutic effects and reducing the frequency of administration for drugs like meloxicam, while maintaining stability and avoiding contamination.
Implementation Method 1
A dry milling process using a mill with milling bodies to produce biologically active material particles with sizes equal to or less than 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.