In this blog post, we will explore how supercritical fluids, particularly carbon dioxide, work in the crystallization process and why they are important for controlling the size and quality of solid particles.
Solubility is the maximum amount of solute that can be dissolved in a given amount of solvent at a constant temperature, and is usually expressed as the mass of solute that can be dissolved in 100 g of solvent. Solubility can vary depending on the properties of the solvent and solute, as well as conditions such as temperature and pressure. A supersaturated mixture is a mixture in which the solute is dissolved beyond its solubility, and such mixtures tend to return to a saturated state. At this point, the solute precipitates as crystals and reaches a stable state. Crystallization is the process in which a saturated mixture becomes supersaturated and the solute precipitates as solid particles. Through the crystallization process, small solid particles can be obtained. This crystallization process is used in the pharmaceutical industry, where the bioavailability of drugs must be increased.
Supercritical fluids are often used in the crystallization process. Substances exist in a supercritical state at temperatures and pressures above their critical temperature and critical pressure. The critical temperature is the highest temperature at which a substance can exist as a liquid, and the critical pressure is the maximum 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 liquid nor gas. In a supercritical state, the distance between molecules of a substance is 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 in a supercritical state or gas state than in a liquid state. In addition, increasing the pressure applied to a supercritical fluid increases its density, allowing it to dissolve more solute, which makes it possible to control the particle size of solids in crystallization processes using supercritical fluids.
In the GAS process, supercritical carbon dioxide is often used as a co-solvent to precipitate the solute dissolved in the mixture into small solid particles. A co-solvent is a substance that does not dissolve the solute but mixes well with the solvent. When a co-solvent is added to the mixture, it mixes with the solvent and the solute precipitates as solid particles. In the GAS process, the material to be crystallized is dissolved in a liquid solvent to form a mixture, which is then filled into a container in an appropriate amount and sealed. Next, the temperature and pressure of the container are adjusted to the critical temperature and critical pressure of carbon dioxide and the liquid solvent, and supercritical carbon dioxide is injected into the container. This causes the mixture to become supersaturated, and the dissolved solute precipitates as solid particles. As the anti-solvent mixes with the solvent, the amount of solute that can be saturated decreases. The amount of solute that precipitates is determined by its concentration, assuming that the amount of the mixture initially filled is the same.
In the crystallization process, when solid particles are precipitated, a certain number of solute molecules must first gather to form aggregates, which then form crystal nuclei. The higher the concentration of the mixture, the more solute molecules can form crystal nuclei, and the more crystal nuclei are formed. When many crystal nuclei are formed, the number of solute molecules that can gather in a single crystal nucleus decreases, and the size of the solid particles becomes smaller.
On the other hand, there is also a crystallization process that uses supercritical carbon dioxide as a solvent. In the RESS process, a mixture of the substance to be crystallized and supercritical carbon dioxide is injected from a high-pressure container into a container maintained at atmospheric pressure. Immediately after spraying, the pressure of the supercritical carbon dioxide rapidly decreases and it turns into a gas, causing the solute to precipitate as solid particles. At this point, crystal nuclei are formed in the mixture, and the principle for determining the particle size of the precipitated solid particles is the same as in the GAS process.
Carbon dioxide is mainly used in crystallization processes such as the GAS process and the RESS process. This is because carbon dioxide has a critical temperature that is not significantly different from room temperature, so it can be easily brought to a supercritical state by slightly raising the temperature and increasing the pressure. Using supercritical carbon dioxide, not only can the particle size of the precipitated solid particles be made smaller by adjusting the pressure, but it is also non-toxic, so there are no safety issues. Solid particles obtained through the crystallization process can be used in various industrial fields. For example, the size and shape of solid particles have an important influence in various fields such as high-performance batteries, nanomaterials, and fine chemicals. Therefore, technological advances in the crystallization process are closely related to the development of these industries.
