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Phase Separation Technology for Microspheres Preparation

CD Formulation offers phase separation technology for the preparation of microspheres, which is a physical type of technology that requires customized solutions that take into account the rate and timing of the preparation process.

Phase Separation TechnologyFig. 1 Microspheres produced by phase separation technology. (Blaker et al.,2005)

Principle of Phase Separation

The principle of phase separation for microsphere preparation is to add a third component, usually an organic non-solvent, to the polymer-drug-solvent system under stirring, with the solubility of the polymer decreasing with the addition of the third component, so that at a specific point in the two phases, phase separation occurs between the solvent and the polymer, resulting in very soft drug-carrying droplets. The system is then transferred to another organic non-solvent, allowing the microspheres to cure to obtain the final microspheres. The method can also be implemented by changing the temperature, pH, and the non-solvent and the polymer that can cause phase separation.

The essence of the phase separation method is the extraction technique, which is a physicochemical phenomenon. Many factors affect the properties of the product, such as the intermolecular interactions of the polymer material, the rate and duration of each step in the preparation process, etc., which are closely related to the quality properties of the microspheres.

Phase Separation Technology

Block copolymer self-assembly technology

The block copolymer selective solvent phase separation method is based on the principle of placing the block copolymer in a solvent, this solvent is a bad solvent in one of the segments to make the polymer chains curl up, but a good solvent in the other segment to make the polymer chains stretch. Again, the block copolymer is placed in another solvent, which is a bad solvent for both blocks. The block copolymer self-assembly method can prepare two-component or multi-component microspheres with different morphologies, which must be selected with a suitable solvent and requires a high level of solvent selection.

Hybrid polymer solvent evaporation phase separation technology

The solvent evaporation phase separation method utilizes two incompatible polymers dissolved in the same solvent. When the solvent evaporates slowly, the two polymers will undergo phase separation due to their different solubility in the solvent, resulting in the formation of microspheres.

Seed polymerization phase separation technology

Usually homogeneous cross-linked or shell-layered spherical particles are used as seeds, and the seeds are swollen with monomer emulsion droplets or solvents at room temperature, and then heated to induce polymerization, which causes the seed particles to be in an unbalanced state due to the interaction of swelling force and elastic stress, resulting in phase separation and extrusion of monomers and oligomers from the particle phase, which eventually prepares the microspheres.

Advantages of Phase Separation Technology

The advantages of phase separation method to prepare microspheres are that it does not require expensive equipment, easy to process in batches, and better sphericity for water-soluble drugs.

In addition to the above microsphere preparation technologies, we can also provide a variety of preparation technologies, including membrane emulsification technology, microfluidic technology, emulsion volatilization technology, etc. Each of these technologies has unique advantages and can bring you convenience. If you are interested in our technologies, please feel free to discuss with us. If you want to customize and produce products, you can contact us, and we will provide services and support that will make you satisfied.


  1. Blaker, J. J., et al. (2005) Novel fabrication techniques to produce microspheres by thermally induced phase separation for tissue engineering and drug delivery. Acta biomaterialia, 4(2), 264-272.
Please note: Our products and services are not intended to be used directly in diagnostic or therapeutic procedures.
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