| dc.description.abstract | The seeding technique is a common method used in the chemical or pharmaceutical industry for achieving good control over the crystal size distribution of the product. Some studies are using a simple empirical equation based on mass balance to estimate the product size from different seed crystal sizes and seed loadings. However, the assumptions provided in this empirical equation makes it enable to be applied in practical situations. Here, we want to focus on modifying the empirical equation by considering the operating parameters such as temperature cooling ranges and seed loadings. This study also aims to promote the proper way to do seeding. To design a seeding crystallization experiment, three important factors would need to be determined: (1) metastable zone width, (2) seed crystal preparation method, and (3) seed loading amount. The batch cooling crystallization of D-mannitol in water was chosen as our model system, operating with 88 to 125μm size seeds and natural cooling, the cooling temperature range and seed loading amount will be the main parameters that change in each set of experiments. Crystal nucleation and crystal growth were monitored by sampling at different time points. The temperature ranges were 40° to 30 °C, 45° to 30 °C, and 48° to 30 °C, the seed loading amounts were 1, 3, and 5wt% of the theoretical yield based on the solubility. The final modified empirical equation is in the form of Lp/Ls=αCs^β, where Lp is the product size, Ls is the seed size, Cs is the seed loading, α=α′exp(-Ea/RTs) that is related to the operation temperature range and β is a constant that changes with the system applied. α will be the variant related to the temperature for understanding the temperature effect where Ea is the activation energy include all the events happened in crystallization process, R is the ideal gas constant, and TS is the seeding temperature. Furthermore, sampling data at different time points were used to get the nucleation and growth behavior shedding some lights on what happened in the process.
The modified empirical seeding equation established in this study provides a fairly accurate prediction of the crystal size produced by the experiments. In a set of verification experiments using a cooling range of 43° to 30 °C and a seed loading amount of 4 wt%, the results were consistent, with a deviation of only about 0.3 % from the predicted value. Even when the process is scaled up, the predictions remain quite accurate, with a deviation of about 4.1 %. Therefore, we can conclude that the experiments conducted in this study can be effectively scaled up using our method. The established empirical formula can predict outcomes accurately, provided that temperature and other conditions are well controlled. Additionally, we attempted to reduce the number of experimental data points to just four sets of experiments. The resulting empirical equation still provided good predictions, demonstrating that even with fewer experiments, reliable predictions can be achieved. | en_US |