Crossflow Membrane Emulsification for Uniform Solid Particles
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for producing solid particulate materials, particularly for pharmaceutical compounds, face challenges in achieving a narrow size distribution and efficient scaling up, especially for compounds with poor solubility and permeability, often requiring high energy inputs and leading to thermal degradation or heterogeneous particle shapes.
Innovation Solution
A crossflow membrane emulsification method is employed, where a liquid phase containing a compound is directed through a membrane with pores, and supersaturation is controlled via cooling or antisolvent precipitation to produce solid particles with a narrow size distribution, suitable for both crystalline and amorphous forms, allowing for continuous and scalable production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Use of energy by stationary object
If conventional crystallisation or re-crystallisation methods are used for purification and control of solid material form and size, then the desired compound can be obtained, but energy consumption is high due to evaporation processes
Solution Approach 1:
The invention changes the fundamental parameter of crystallisation from evaporative removal of solvent to antisolvent addition. By adding a second solvent (antisolvent) in which the compound is insoluble or poorly soluble, the solution becomes supersaturated and crystallisation occurs without energy-intensive evaporation, thus reducing energy consumption while maintaining control over crystal form and size through selection of appropriate antisolvent and process conditions
Solution Approach 2:
The invention introduces an intermediary substance (antisolvent) that mediates the crystallisation process. The antisolvent acts as a bridge between the dissolved compound and the solid crystal form, enabling precipitation by reducing solubility without requiring thermal energy input for evaporation, thereby resolving the contradiction between low energy consumption and controlled crystallisation
2Manufacturing precision
If mechanical milling or high pressure homogenization is used to increase surface area, then bioavailability can be improved, but thermal degradation and heterogeneous particle shapes occur
Solution Approach 1:
The invention replaces mechanical post-treatment methods (milling, homogenization) with a controlled crystallisation process that directly produces particles of desired size and shape. By controlling supersaturation level, antisolvent addition rate, and mixing conditions, the process generates uniform particles with high surface area without subjecting the compound to mechanical stress or thermal degradation, thus eliminating harmful effects while achieving the desired manufacturing precision
Solution Approach 2:
The invention performs the surface area enhancement action during the crystallisation step itself rather than as a subsequent mechanical treatment. By controlling nucleation and crystal growth conditions to produce fine, uniform particles directly, the desired surface area is achieved preliminarily, avoiding the need for later mechanical processing that would cause thermal degradation and shape heterogeneity
3Productivity
If reverse antisolvent precipitation is used, then small solid particles are formed quickly, but narrow size distribution and scalability are difficult to achieve
Solution Approach 1:
The invention introduces dynamic control elements to the antisolvent precipitation process, including controlled addition rate of antisolvent, adjustable mixing intensity, and temperature control. These dynamic parameters allow optimization of both production speed and particle size distribution uniformity, enabling the process to achieve narrow size distribution while maintaining high productivity and scalability that static conventional methods cannot achieve
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 uniform solid particles with controlled size distribution, improving bioavailability and scalability, while reducing energy consumption and avoiding thermal degradation, making it suitable for poorly soluble pharmaceutical compounds.
Implementation Method 1
a membrane defining a plurality of pores
Implementation Method 2
controlling the supersaturation of the liquid phase after it has passed through the membrane via the plurality of pores
Implementation Method 3
precipitation is induced by the addition of second solvent in which the compound is insoluble or poorly soluble, an antisolvent
Implementation Method 4
The solvents are selected such that the compound of interest is partially soluble in one solvent, referred to as 'the solvent' and substantially insoluble in the other solvent, referred to as 'the anti-solvent'
Data Source
AI summary
There is described a method of preparing solid particles of a compound, said method comprising controlling provision of a liquid phase, wherein said liquid phase comprises a solution of the compound, in a first flow direction to a membrane, said membrane defining a plurality of pores; and controlling the supersaturation of the liquid phase after it has passed through the membrane via the plurality of pores, to form solid particles of the compound. The method may comprise a continuous method.