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作者 Svang-Ariyaskul, Apichit
書名 Chiral separation using hybrid of preferential crystallization moderated by a membrane barrier
國際標準書號 9781124087207
book jacket
說明 219 p
附註 Source: Dissertation Abstracts International, Volume: 71-07, Section: B, page: 4398
Adviser: Ronald W. Rousseau
Thesis (Ph.D.)--Georgia Institute of Technology, 2010
Chiral separation was proposed using a novel hybrid of preferential crystallization and a membrane barrier. The main objective of this work is to establish a new alternative chiral separation process that increases the product yield and purity from the existing processes. This work is primarily based on experiments. The process simulations were carried out for experimental planning and for helping explain the system behavior. The process simulations were also carried out to study the effects of process variables at the conditions beyond the feasible of the available experimental set ups
A crystallizer was divided into two separated vessels attached with a membrane. The selected membrane should be able to block the crystals from moving between vessels but allow high mass diffusion of the solutes. The operating conditions must be well-controlled so that the product yield increased from current processes while high purity product was maintained. The fundamentals of the new process are that the operating conditions must be controlled so that the pure enantiomers are produced on opposite sides of a membrane, which acts simply as a physical barrier to block crystals from moving between isolated chambers. The crystallization process starts with racemate mother liquor in different chambers on either side of the membrane. Seed crystals of each enantiomer are introduced into different vessels so that such crystal will grow and remain enotiomerically pure. Therefore, the increase of product yield and purity are expected. In this work, the separation of DL-glutamic acid was studied as a test model. DL-glutamic acid was a racemic conglomerate which was appropriate for the separation by our hybrid process. L-glutamic acid is an important feed stock for the production of mono sodium glutamate which is used globally as a food flavor enhancement
The solubility and metastable limits were measured as process boundaries. The solubility is a thermodynamic variable while the metastable limit is a kinetic variable changing upon the system dynamic, in this case, the cooling rate. The faster the cooling rate is, the further away the metastable limit is from the solubility. The concentrations of the undesired species must not reach the metastable limit; otherwise, the undesired species will crystallize as impurity
Preliminary experiments of DL-glutamic acid resolution were carried out through the set up with a flat plate membrane. The investigation was carried out with two amounts of seed mass (3.50 and 25.22 g/dm3 crystallizer) at a cooling rate of 1.0°C/h. The results showed that the more the seed mass was introduced, the more the final products were recovered because the crystallizing surface increased. The preliminary experimental results showed that this process is feasible. The product yield increased up to 65% from preferential crystallization and the product purity was up to 94%. The adjusted overall crystal growth rate was also estimated here
The experimental and simulation results showed that the effects from mass transfer resistance due to bulk diffusion were not important while the effects from mass transfer resistance from transmembrane diffusion and surface integration were important. Therefore, the set up with hollow fiber membranes was used in the future to reduce a transmembrane resistance by increasing the membrane area. The surface integration resistance depends on the crystallizing surface area and could be reduced by the increase of seed mass
For the advanced set up with hollow fiber membranes, the experiments were carried out at various amounts of seed crystals (3.98, 10.09, 25.22, and 74.87 g/dm3 crystallizer) and cooling rates (0.2, 0.5, 1.0, 5.0, and 10.0°C/h) to investigate on these effects on the system behaviors and the product yield and purity. The experimental results showed that the larger the amount of the seed mass was, the larger the amount of product was recovered because of larger crystallizing surface area. The change of the cooling rate affected the metastable limit gap and the run time. If the cooling rate was too slow at 0.2oC/h, the metastable limit gap was too narrow and the metastable limit was reached. If the cooling rate was too fast at 5.0 and 10.0oC/h, the run time was insufficient for both crystallization of desired species and export of undesired species; therefore, the metastable limit was reached. The cooling rates of 0.5 and 1.0°C/h were feasible and the metastable limit was not reached. The amount of product from cooling rate of 0.5°C/h was higher than the one from cooling rate of 1.0°C/h because longer time was provided for crystallization of desired species. The product purity from the successful experiments was over 99.7% which was considered pure (Mullin, 2001)
The experiments and simulations were carried out further to find the desirable amount of seed mass that gave product yield close to the amount of seed mass and the amount of maximum possible yield. The experiments were run using the 10.09 g seed mass/dm3 crystallizer at the cooling rate of 0.5°C/h. The product purity was over 99.7%. The product yield was 65% of the seed mass and 70% of maximum possible yield. This yield was satisfactory. The yield enhancement was up to 283% from preferential crystallization and this enhancement showed that this process was revolutionary
The major innovation of this work is an establishment of a novel chiral separation process using preferential crystallization coupled with a membrane barrier. This hybrid process was proved to be promising from a significant increase in product yield and purity compared to existing chiral separation processes. This work sets up a process design platform to extend the use of this hybrid process to a separation of other mixtures. This novel process especially is a promising alternative for chiral separation of pharmaceutical compounds which include more than fifty percent of approved drugs world-wide. A better performance chiral separation technique contributes to cut the operating cost and to reduce the price of chiral drugs
School code: 0078
Host Item Dissertation Abstracts International 71-07B
主題 Engineering, Chemical
0542
Alt Author Georgia Institute of Technology
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