Nucleation

Cocrystal Solubility Advantage Diagrams as a Means to Control Dissolution, Supersaturation, and Precipitation

“…The observed DSP dependence on SA follows the nucleation rate dependence on supersaturation, , where spontaneous nucleation occurs above a threshold or critical supersaturation. Below this supersaturation level, there is no instantaneous nucleation and supersaturation levels are sustained.…”

Seeding Techniques and Optimization of Solution Crystallization Processes

“…It was found that with a larger amount of seeds, the ratio of the amount of seeds used to the number of crystals produced increased significantly. This outcome was explained by agglomeration being a major factor, and an increase in impurities is suggested as a result . Furthermore, the amount of seeds used depends on the shape of the crystal.…”

“…The seed loading amount can vary from 0.1 to 15 wt % or even up to 50 wt % of theoretical product yield; the value largely depends on the preferred characteristics of the final product as well as the inherent properties of the secondary nucleation and growth kinetics. Gong and Tang proposed four levels of seed loading amount that correspond to different optimization targets: trace addition (∼0.1 wt %), small addition (∼1 wt %), large addition (∼10 wt %), and massive addition (>10 wt %) . Typically, if control of nucleation is desired (e.g., to avoid spontaneous nucleation or metastable oiling out that occurs with fast crystallization kinetics), a trace number of seeds is required to stabilize the process.…”

“…Gong and Tang proposed four levels of seed loading amount that correspond to different optimization targets: trace addition (∼0.1 wt %), small addition (∼1 wt %), large addition (∼10 wt %), and massive addition (>10 wt %). 68 Typically, if control of nucleation is desired (e.g., to avoid spontaneous nucleation or metastable oiling out that occurs with fast crystallization kinetics), a trace number of seeds is required to stabilize the process. In contrast, a large or massive amount of seeds that can facilitate crystal growth in a system with slow kinetics is required to achieve large-sized crystals with a narrow CSD, while tuning of the crystal size and CSD along with the seed loading amount coupled with consideration of the seed attributes must be determined.…”

“…This outcome was explained by agglomeration being a major factor, and an increase in impurities is suggested as a result. 68 Furthermore, the amount of seeds used depends on the shape of the crystal. Needlelike crystals require more seeds since they have less surface area on which crystals can grow, whereas rodshaped crystals would require fewer seeds.…”