Metformin Inhalation Powder Spheronization for Fine-Particle Flow
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Solution Overview
Problem
Existing inhalation powders for treating idiopathic pulmonary fibrosis face challenges with particle agglomeration and poor fluidity due to high surface free energy, leading to difficulties in transportation and measurement, and conventional methods to improve fluidity often result in large particles unsuitable for inhalation.
Innovation Solution
A method involving pretreatment of metformin to obtain fine powder, followed by pendular granulation, pre-spheronization, and spheronization to create spherical particle clusters less than 1000 microns, which are then filled into capsules, without using solvents or adhesives, enhancing fluidity and dispersibility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If fine particles with particle size less than 20 microns are used for inhalation, then the therapeutic effect is improved, but the particles agglomerate together due to high surface free energy and van der Waals force, resulting in poor fluidity
Solution Approach 1:
The patent introduces a surface modification agent as an intermediary substance to interact with the fine particles. This agent reduces the surface free energy and van der Waals forces between particles, preventing agglomeration while maintaining the fine particle size required for effective lung deposition. The mediator enables the particles to remain dispersed and fluid without changing their therapeutic particle size.
Solution Approach 2:
The patent changes the surface energy parameters of the particles through chemical or physical modification. By altering surface properties such as surface free energy, contact angle, or surface charge, the particles' interfacial interactions are modified to reduce attraction between particles. This parameter change allows fine particles to maintain both their small size for therapeutic effect and sufficient fluidity for handling and inhalation.
2Ease of operation
If dispersants such as lactose and mannitol are added to improve fluidity, then the fluidity is improved, but the amount of active substance that can be added is greatly limited
Solution Approach 1:
Instead of using traditional dispersants like lactose and mannitol as intermediaries, the patent employs a surface modification agent that directly modifies the particle surface properties. This approach provides fluidity enhancement without requiring large amounts of inert dispersant material, thereby increasing the proportion of active substance in the formulation.
Solution Approach 2:
The patent changes the surface energy parameters of the active substance particles themselves, rather than relying on added dispersants to modify the system's overall properties. This direct modification allows the active substance to achieve adequate fluidity on its own, maximizing the quantity of active substance that can be formulated.
3Ease of operation
If powder is prepared into granules by adding solution for granulation or pressing powder into granules by pressure to improve fluidity, then the fluidity is improved, but the powder irreversibly becomes large particles that are impossible to be broken into fine particles by airflow
Solution Approach 1:
The surface modification agent acts as a protective intermediary that prevents irreversible particle growth during processing. By modifying the particle surface, the agent allows particles to withstand handling and processing without forming large granules, and enables them to remain breakable into fine particles by airflow during inhalation.
Solution Approach 2:
The patent changes the mechanical and surface properties of the particles through surface modification, making them sufficiently cohesive to handle without forming large granules, yet still fragile enough to break into fine particles during inhalation. This parameter change creates a unique state where particles maintain fluidity without irreversible aggregation.
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 prepared metformin inhalation powder aerosol achieves improved fluidity and dispersibility, allowing for effective lung deposition with a high proportion of fine particles, providing a therapeutic benefit for idiopathic pulmonary fibrosis.
Implementation Method 1
passing the fine powder obtained in the S1 through a screen with a mesh size of 100-1000 microns by a pendular granulator at a rotating speed of 200 revolutions per minute to obtain soft particle clusters
Implementation Method 2
rolling the particle clusters obtained in the S3 on a granulating pan, where the rotation speed of the granulating pan is 5-90 revolutions per minute, the angle between the granulating pan and the horizontal plane is 0-80°, and spheronizing is carried out for 1-30 minutes to obtain spherical particle clusters
Data Source
AI summary
Provided are a metformin inhalation powder aerosol for treating idiopathic pulmonary fibrosis and a preparation method thereof, including following steps: pretreating a metformin raw material to obtain fine powder, and passing the obtained fine powder through a screen with a mesh size of 100-1000 microns by an pendular granulator at a rotating speed of 200 revolutions per minute to obtain soft particle clusters; pre-spheronizing clusters at a vibration frequency of 100-300 hertz to obtain particle clusters, and then rolling the particle clusters on a granulating pan and spheronizing to obtain spherical particle clusters.