Why are supercritical fluids and carbon dioxide important in the crystallization process?

Solubility is the amount of solute that can dissolve in 100 grams of solvent at a given temperature. GAS and RESS crystallization processes use supercritical carbon dioxide to precipitate solid particles, which are used in a variety of industries, including pharmaceuticals, batteries, and nanomaterials. Supercritical fluids are essential for efficient crystallization processes due to their high solubility and controllability of particle size.

 

Solubility is the maximum amount of solute that can be dissolved in a certain amount of solvent at a certain temperature, usually the mass of solute that can be dissolved in 100 grams of solvent. Solubility can vary depending on the properties of the solvent and solute, as well as conditions such as temperature and pressure. Supersaturation of a mixture is when a solute is dissolved above its solubility, and a supersaturated mixture tends to return to saturation. This is when the solute precipitates out as crystals and finds a stable state. Crystallization is the process by which a saturated mixture becomes supersaturated and the solute precipitates out as solid particles. This crystallization process is used in the pharmaceutical field, for example, to increase the bioavailability of drugs.
Crystallization processes often use supercritical fluids. A substance exists in a supercritical state above a critical temperature and a critical pressure. The critical temperature is the highest temperature at which a substance can exist as a liquid, and the critical pressure is the highest pressure at which a substance can exist as a gas. When the temperature and pressure are above the critical temperature and critical pressure, the substance exists in a supercritical state, which is neither a liquid nor a gas. In the supercritical state, the distances between the molecules of a substance are closer than when the substance is a gas, but not as close as when it is a liquid. Solutes and solvents can move more freely when a substance is supercritical or a gas than when it is a liquid. In addition, increasing the pressure applied to the supercritical fluid increases its density, which allows it to dissolve larger amounts of solute, so crystallization processes using supercritical fluids can control the size of the solid particles.
In GAS processes, supercritical carbon dioxide is often used as a semi-solvent to precipitate solutes dissolved in a mixture into small particle size solids. When a semi-solvent is added to a mixture, the semi-solvent mixes with the solvent and the solute precipitates out as solid particles. In the GAS process, the substance to be crystallized is dissolved in a liquid solvent to form a mixture, filled into a container, and the container is sealed. The temperature and pressure of the vessel are then adjusted between the critical temperature and critical pressure of the carbon dioxide and the liquid solvent, and supercritical carbon dioxide is injected into the vessel. The mixture then becomes supersaturated and the dissolved solute precipitates out as solid particles. As the semi-solvent mixes with the solvent, the amount of solute that can be saturated is reduced. The amount of solute that precipitates is determined by the concentration of the initially filled mixture, provided that the volume is the same.
In order to precipitate solid particles in a crystallization process, a certain number of solute molecules must first come together to form aggregates, which form the crystal nucleus. The higher the concentration of the mixture, the more solute molecules that can form a crystal nucleus, resulting in more crystal nuclei. The more crystal nuclei, the fewer solute molecules that can gather in one crystal nucleus, resulting in smaller solid particles.
There are also crystallization processes that use supercritical carbon dioxide as a solvent. In the RESS process, a mixture of the material to be crystallized and supercritical carbon dioxide is injected from a vessel at high pressure into a vessel at atmospheric pressure. Immediately after injection, the supercritical carbon dioxide quickly depressurizes and turns into a gas, precipitating the solute into solid particles. Crystalline nuclei are produced in the mixture, and the principle of determining the particle size of the precipitated solid particles is the same as in the GAS process.
In crystallization processes such as GAS and RESS processes, carbon dioxide is mainly used. This is because the critical temperature of carbon dioxide is not much different from room temperature, so it can be easily made supercritical by raising the temperature and pressure slightly. Supercritical carbon dioxide not only makes it possible to adjust the pressure to make the particle size of the precipitated solid particles smaller, but it is also non-toxic and therefore free from safety concerns. The solid particles obtained through the crystallization process can be used in a variety of industries. For example, in many fields such as high-performance batteries, nanomaterials, and fine chemicals, the size and shape of solid particles have an important impact. Therefore, technological advances in crystallization processes are closely related to the development of these industries.