The Influence of the Solid Solution Formation on Purification of L-Menthol from the Enantiomer Mixture by Three-Phase Crystallization.

Three-phase crystallization (TPC) was introduced in this study to purify L-menthol from menthol enantiomer mixtures in consideration of the formation of solid solutions. TPC is a new separation technology, which combines melt crystallization and vaporization to result in the desired crystalline product from a liquid mixture along with the unwanted components vaporized via the three-phase transformation by reducing temperature and pressure. The three-phase transformation conditions for the liquid menthol enantiomer mixtures were determined based on the thermodynamic calculations to direct the TPC experiments. A new model was proposed based on the mass and energy balances in consideration of the formation of the solid solutions to predict the yield and purity of the final L-menthol product during TPC. The yield and purity obtained from the TPC experiments were compared with those predicted by the model.

Comparison of the Nucleation Kinetics Obtained from the Cumulative Distributions of the Metastable Zone Width and Induction Time Data.

A linearized integral model based on classical nucleation theory is applied in this work to determine the interfacial energy and pre-exponential factor using a linear plot from the cumulative distributions of the metastable zone width (MSZW) data for some systems reported in the literature, including isonicotinamide, butyl paraben, dicyandiamide, and salicylic acid. Based on the same criterion for the nucleation point, the interfacial energy and pre-exponential factor are determined using the conventional linear regression method from the cumulative distributions of the induction time data for the same systems. The results indicate that the interfacial energy and pre-exponential factor calculated from the MSZW data are consistent with those calculated from the induction time for the studied systems.

Purification of Chlorophenol Isomers by Stripping Crystallization Combining Melt Crystallization and Vaporization.

Stripping crystallization (SC) was introduced in this work to purify p-chlorophenol from the p-chlorophenol-rich liquid mixture and to purify m-chlorophenol from the m-chlorophenol-rich liquid mixture, respectively. Essentially, SC combines melt crystallization and vaporization to produce the solid product and the vapor from a liquid mixture via a series of three-phase transformations at reduced pressures during the cooling process. At the end of the SC, only the solid product remained while the liquid mixture was almost eliminated and the produced vapor was removed. A set of differential equations based on the mass and energy balances were proposed to determine the incremental variations of the amounts of remaining liquid, produced solid and produced vapor during the batch SC process. The experimental yield and product purity of the final product obtained from the batch SC experiments were compared with those predicted by the model.

Chiral Separation of the Phenylglycinol Enantiomers by Stripping Crystallization.

Stripping crystallization (SC) is introduced in this work for chiral purification of R-phenylglycinol from the enantiomer mixture with an initial concentration ranging from 0.90 to 0.97. As opposed to the solid⁻liquid transformation in melt crystallization, the three-phase transformation occurs in SC at low pressures during the cooling process. SC combines melt crystallization and vaporization to produce a crystalline product and mixture vapor from a mixture melt due to the three-phase transformation. Thermodynamic calculations were applied to determine the operating pressure for the three-phase transformation during the cooling process in the SC experiments. To consider the possible deviations between the calculated and the actual three-phase transformation conditions, the product purity and the recovery ratio of R-phenylglycinol were investigated within a range of operating pressures during the cooling process.

Modeling solute clustering in the diffusion layer around a growing crystal.

The mechanism of crystal growth from solution is often thought to consist of a mass transfer diffusion step followed by a surface reaction step. Solute molecules might form clusters in the diffusion step before incorporating into the crystal lattice. A model is proposed in this work to simulate the evolution of the cluster size distribution due to the simultaneous aggregation and breakage of solute molecules in the diffusion layer around a growing crystal in the stirred solution. The crystallization of KAl(SO(4))(2)12H(2)O from aqueous solution is studied to illustrate the effect of supersaturation and diffusion layer thickness on the number-average degree of clustering and the size distribution of solute clusters in the diffusion layer.

Investigations into the Influence of Solvents on the Nucleation Kinetics for Isonicotinamide, Lovastatin, and Phenacetin.

A new method of data interpretation based on classical nucleation theory is proposed in this work to elucidate the influence of solvents on the pre-exponential nucleation factor and interfacial energy using the induction time data for three crystallization systems, including isonicotinamide, lovastatin, and phenacetin. In this method, the pre-exponential nucleation factor is replaced by the intrinsic nucleation factor multiplied by temperature and divided by solution viscosity. The proposed method is applied to study the nucleation kinetics of isonicotinamide, lovastatin, and phenacetin among various solvents using the induction time data measured in this work. The results indicate that the intrinsic nucleation factor increases linearly with increasing square root of interfacial energy in various solvents for each system.

Using a fed-batch culture strategy to enhance rAAV production in the baculovirus/insect cell system.

Recombinant adeno-associated virus (rAAV) is one of the most promising vectors for human gene therapy. However, the production systems that are currently available have a limited capacity and cannot provide sufficient quantities of rAAV for preclinical or clinical trials. Many novel methods for improving rAAV production have been developed, but few researchers have focused on the culture process. In this study, we use a fed-batch culture system to enhance rAAV yield in the baculovirus/insect cell system. When the insect cells were co-infected with MOI=5 of Bac-GFP at a ratio of 1:9:9 (Bac-GFP: Bac-Rep: Bac-VP), the fed-batch culture achieved optimal rAAV yields. In batch culture, the optimal cell density for producing rAAV was found to be 1x10(6) cells/ml, and the highest rAAV yield (1.22x10(8) IVP/ml, 122 IVP/cell) occurred at day 5 post-infection. In the fed-batch culture, rAAV yield reached 2.13x10(8) IVP/ml at day 4 post-infection, and the highest rAAV yield was 2.40x10(8) IVP/ml (240 IVP/cell) at day 5 post-infection. The cost of the batch and fed-batch cultures is similar; however, the rAAV yield was 2.6-fold higher in the fed-batch culture system compared with that in the batch culture system. Therefore, here we demonstrated an economical and efficient strategy for rAAV production.