Nanobubble Water Crystallization for Uniform Pharmaceutical Particles
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Solution Overview
Problem
Current methods for producing solid particles of poorly water-soluble pharmaceutical compounds using crystallization techniques face challenges in achieving uniform particle size distribution and high dispersibility, often requiring energy-intensive processes and additional microparticulation treatments, which increase costs and complexity.
Innovation Solution
The use of nanobubble water or aqueous nanobubble solutions as a poor solvent in the crystallization method allows for the production of microparticulate solid particles with uniform size distribution, eliminating the need for post-precipitation microparticulation treatments and reducing the number of sterilization steps, thereby improving dispersibility and reducing patient burden during injection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional poor solvent crystallization is used to produce solid particles of poorly water-soluble pharmaceutical compounds, then the process is simple and cost-effective, but the particle size distribution is non-uniform and dispersibility is poor
Solution Approach 1:
The invention changes the physical-chemical parameters of the poor solvent by introducing nanobubbles (gas phase) into the liquid solvent, creating nanobubble water or nanobubble-containing aqueous solutions. This parameter change fundamentally alters the crystallization process, enabling uniform particle size distribution (0.1-10 μm) and excellent dispersibility without requiring additional microparticulation treatments.
2Manufacturing precision
If high-pressure crystallization apparatus or homogenizers are used to achieve uniform particle size, then particle size uniformity is improved, but energy consumption increases significantly
Solution Approach 1:
The invention replaces mechanical microparticulation systems (high-pressure homogenizers, ultrasonic generators) with a chemical-physical approach using nanobubble-containing solvents. The nanobubbles act as nucleation sites during crystallization, enabling uniform particle formation without the need for high-energy mechanical disruption processes after precipitation.
3Length of moving object
If wet-milling apparatus is used for microparticulation, then particle size is reduced, but operation time increases and yield decreases
Solution Approach 1:
The invention performs preliminary action by incorporating nanobubbles into the poor solvent before the crystallization process. These pre-formed nanobubbles serve as nucleation sites that guide crystal growth, resulting in uniformly small particle sizes (0.1-10 μm) directly from the precipitation process, eliminating the need for subsequent time-consuming wet-milling operations.
4Manufacturing precision
If additional microparticulation treatments are applied after precipitation, then particle size uniformity is improved, but process complexity and production costs increase
Solution Approach 1:
The invention enables the poor solvent to perform the microparticulation function inherently through the presence of nanobubbles. During crystallization, the nanobubbles act as nucleation sites that automatically control particle size and distribution, making the solvent self-sufficient for producing uniform microparticles without requiring external microparticulation equipment or additional processing steps.
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 solid particles with enhanced dispersibility and stability, enabling the use of thinner injection needles and reducing production costs and complexity, while maintaining the purity and yield of the pharmaceutical compounds.
Implementation Method 1
Crystallization method is a method of precipitating crystals by utilizing crystallization phenomenon in a non-equilibrium state, where-supersaturation is a driving power
Implementation Method 2
The poor solvent crystallization method is a method including dissolving a compound, which is insoluble in water and the like, in a good solvent, and mixing the compound solution with another solvent (water etc.) to allow for precipitation of crystals by creating a supersaturation state of the solution
Implementation Method 3
preparing nanobubble water or an aqueous nanobubble solution by a pressurized dissolution method wherein a gas is pressurized to be dissolved in water or in an aqueous solution at supersaturation, the solution is rapidly depressurized to allow generation of microbubbles having a diameter of 1-60 μm and nanobubbles having a diameter of less than 1 μm
Data Source
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AI summary
A method of producing crystal of a poorly water-soluble pharmaceutical compound, including mixing a solution of a poorly water-soluble pharmaceutical compound in a good solvent and nanobubble water or an aqueous nanobubble solution to precipitate crystal of the poorly water-soluble pharmaceutical compound. The crystal of a poorly water-soluble pharmaceutical compound obtained by the method is microparticulate and has more uniform particle size distribution, and is superior in the absorbability and sustainability.