Supercritical Fluid Expansion for Pharmaceutical Particle Formation
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Solution Overview
Problem
Current methods for producing nanoparticles of active substances are complex, often require high temperatures, multiple steps, and the use of toxic solvents, leading to stability issues and inefficiencies in creating stable pharmaceutical forms, especially for heat-sensitive substances and those with decreasing solubility in supercritical fluids.
Innovation Solution
A process involving the expansion of a supercritical solution in an enclosure with a divided solid, where part of the fluid is in liquid form during expansion, allowing for the production of micron and submicron particles without high temperatures and reducing the need for numerous excipients, resulting in a dry, stable solid composition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If high-pressure homogenization or nanogrinding processes are used to produce nanoparticles, then particle size is reduced and dissolution rate increases, but the process complexity increases and requires multiple manufacturing steps
Solution Approach 1:
The patent uses phase transition of a supercritical fluid (CO2) to a liquid state upon depressurization, causing the dissolved active substance to precipitate as fine particles. This phase change-driven particle formation eliminates the need for complex mechanical grinding or homogenization processes, directly producing nanoparticles through a single-step precipitation mechanism.
Solution Approach 2:
The patent replaces mechanical size reduction methods (high-pressure homogenization, nanogrinding) with a chemical-physical precipitation process. Instead of using mechanical force to break down particles, the invention uses controlled phase transition and supersaturation to form particles de novo, substituting mechanical systems with a phase-change-based system.
2Manufacturing precision
If high temperatures are applied during nanoparticle production, then dissolution rate increases, but heat-sensitive active substances may be degraded
Solution Approach 1:
The patent utilizes the phase transition of supercritical CO2 to liquid CO2 upon depressurization as the driving force for particle formation. This phase change occurs at or near ambient temperatures, enabling particle production without thermal exposure. The process leverages the thermodynamic properties of supercritical fluids to achieve particle formation through pressure change alone, avoiding thermal degradation of heat-sensitive compounds.
3Stability of the object's composition
If multiple manufacturing steps are used to produce stable nanoparticle formulations, then particle stability improves, but the production time and process complexity increase
Solution Approach 1:
The patent combines particle formation, drying, and formulation into a single integrated process step. The supercritical fluid extraction and precipitation occur simultaneously, and the resulting dry particles are obtained directly without separate drying or formulation steps. This merging of operations reduces production time while maintaining particle stability through the inherent properties of the supercritical fluid process.
Solution Approach 2:
The supercritical CO2 acts as both the processing medium and the drying agent. Upon depressurization, the CO2 transitions to liquid and then evaporates, automatically removing solvent and drying the particles in situ. This self-drying mechanism eliminates the need for separate drying steps and reduces overall process time while ensuring particle stability.
4Quantity of substance
If conventional drying methods are applied to nanoparticle dispersions, then the product can be converted to dry form, but the nanoparticles may aggregate and lose their fine particle characteristics
Solution Approach 1:
The patent replaces conventional mechanical drying methods (which cause particle aggregation) with a phase-transition-based drying mechanism. The supercritical CO2 naturally evaporates upon depressurization, creating a gentle drying environment that preserves particle morphology. This substitution of drying mechanism prevents aggregation and maintains the fine particle size distribution throughout the drying process.
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 the production of stable, crystalline submicron particles with improved bioavailability, simplifying the process by eliminating the need for multiple steps and toxic solvents, and allowing for easy conversion into various pharmaceutical forms suitable for different administration routes.
Implementation Method 1
expanding said solution in an enclosure under pressure and temperature conditions for which part of the fluid is in liquid form during expansion
Implementation Method 2
forming a solution of the active substance in a fluid at supercritical pressure
Data Source
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AI summary
The present invention relates to a method for preparing solid pharmaceutical compositions comprising fine particles of at least one active substance, dispersed on and (or) within a divided solid. This method is characterized in that a solution is formed which comprises at least one active substance in a fluid at supercritical pressure, said solution then being expanded in a chamber under temperature and pressure conditions for which a part of said fluid is in the liquid state at the time of the expansion, said fluid thus expanded being brought into contact with a divided solid in said chamber.