multisolvents

Multisolvents are solvent systems composed of two or more solvents used in combination to dissolve solutes or to tailor processing conditions. In contrast to single-solvent systems, multisolvent mixtures expand the range of achievable solubility by adjusting properties such as polarity, dielectric constant, and Hansen solubility parameters. By varying the composition, researchers can often dissolve compounds that are poorly soluble in a single solvent and control dissolution rates, crystallization, and phase behavior.

Key concepts in multisolvent design include matching the solubility parameters between solute and solvent mixture, as well as considering the effective polarity and cohesive energy density of the mixture. Activity coefficients, miscibility, and potential azeotropes influence how solutes behave in mixed solvents. Temperature dependence is also important, since solubility in solvent mixtures can change nonlinearly with temperature, enabling strategies for separation or crystallization.

Common applications span pharmaceutical formulation, chemical synthesis, crystallization processes, and liquid-liquid extractions. Multisolvent systems are used to dissolve poorly soluble active ingredients, adjust solvent strengths during reaction workups, tune precipitation and crystallization for purer products, and create mobile phases for chromatography with improved selectivity.

Design considerations involve selecting solvent components for desired polarity range, assessing miscibility and phase behavior, evaluating safety and environmental impact, and guiding experimental optimization with solubility measurements and, when available, predictive models. Limitations include increased formulation complexity, potential formation of undesired phases, regulatory and toxicity concerns, and cost and handling challenges.

Examples include water–ethanol, water–acetone, and water–dimethyl sulfoxide blends, as well as more complex ternary mixtures used in specialized purification and crystallization workflows.