Antisolventkiteytys

Antisolventkiteytys is a crystallization technique in which a solute is dissolved in a solvent in which it has adequate solubility, and an anti-solvent—one in which the solute has low solubility—is added to induce crystallization. The anti-solvent reduces solubility through dilution, changes in solvent quality, or phase behavior, generating supersaturation that promotes nucleation and crystal growth. It is used in pharmaceuticals, fine chemicals, and materials science to tailor crystal size, morphology, or polymorphism.

Principle: The process depends on miscibility of solvent and anti-solvent and their effect on solute solubility. Local supersaturation during mixing triggers nucleation; subsequent growth forms crystals. Parameters such as addition rate, temperature, agitation, and presence of seeds or additives influence the balance between nucleation and growth, affecting particle size distribution and habit.

Process approaches: In batch antisolvent crystallization, one phase is prepared and anti-solvent is added under controlled conditions. In continuous setups, streams of solvent, solute solution, and anti-solvent are metered and mixed in mixers or microreactors. Equipment includes stirred crystallizers, static mixers, and solvent-switch crystallizers. Temperature and flow control are essential.

Crystal properties and control: The solvent/anti-solvent pair, temperature, and additives determine solubility curves, polymorphism, and morphology. Seeding can direct crystallization; additives may suppress undesired nucleation. Rapid precipitation often yields small, broad particle-size distributions or agglomerates and can lead to undesired polymorphs.

Applications and limitations: Antisolventkiteytys can produce crystals from solutes with limited solubility or where solvent recovery is advantageous. It enables control of particle size, purity, and sometimes polymorphs. Limitations include scale-up challenges, sensitivity to mixing, potential solvent incompatibilities, and risk of uncontrolled nucleation or impurity incorporation.