This review discusses important research developments and arising challenges in the field of industrial crystallization with an emphasis on recent problems. The most relevant areas of research have been identified. These are the prediction of phase diagrams; the prediction of effects of impurities and additives; the design of fluid dynamics; the process control with process analytical technologies (PAT) tools; the polymorph and solvate screening; the stabilization of non-stable phases; and the product design. The potential of industrial crystallization in various areas is outlined and discussed with particular reference to the product quality, process design, and control. On this basis, possible future directions for research and development have been pointed out to highlight the importance of crystallization as an outstanding technique for separation, purification as well as for product design.

Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations: the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin’s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. Yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin’s oral bioavailability. In this review of our group’s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide (CPP) to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPP-insulin conjugates could facilitate cellular uptake of insulin while keeping insulin’s biologic functions intact. It was also confirmed that low molecular weight protamine (LMWP) behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan (25 wt-%) and silica (75 wt-%) exhibited the greatest mucoadhesion at gastric pH. Furthermore, drug release from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

With the hope of overcoming the serious side effects, great endeavor has been made in tumor-targeted chemotherapy, and various drug delivery modalities and drug carriers have been made to decrease systemic toxicity caused by chemotherapeutic agents. Scientists from home and abroad focus on the research of targeted microbubbles contrast agent, and the use of the targeted ultrasound microbubble contrast agent can carry gene drugs and so on to the target tissue, as well as mediated tumor cell apoptosis and tumor microvascular thrombosis block, etc., thus plays the role of targeted therapy. Recent studies have elucidated the mechanisms of drug release and absorption, however, much work remains to be done in order to develop a successful and optimal system. In this review, we summarized the continuing efforts in understanding the usage of the ultrasound triggered target microbubbles in cancer therapy, from release mechanism to preparation methods. The latest applications of ultrasound-triggered targeted microbubbles in cancer therapy, especially in gene therapy and antiangiogenic cancer therapy were discussed. Moreover, we concluded that as a new technology, ultrasound–triggered targeted microbubbles used as drug carriers and imaging agents are still energetic and are very likely to be translated into clinic in the near future.

Oriented stratum corneum model lipid membranes were used to study the influence of the short chain ceramides (CER)[NP] and [AP] as well as the impact of the lipophilic penetration enhancer molecules oleic acid (OA) and isopropyl myristate (IPM) on the lipid nanostructure. The influence of the enhancer molecules were studied using specifically deuterated OA and IPM and neutron diffraction. ²H NMR spectroscopy was used to study the impact of the ceramides’ degree of order within the stratum corneum model lipid membranes. It was found that CER[NP] forms two very stable phases with high resistance against temperature increase. Phase B showed unusual hydration behavior as no water uptake of this phase was observed. The ²H NMR spectroscopic measurements showed that CER[NP] based ternary model system had a higher state of lamellar order in comparison to CER[AP] based lipid matrix.

The studies confirmed that the short chain ceramides, particularly CER[NP], have a very high impact on the integrity of the Stratum corneum lipid bilayers. The penetration enhancer OA has not influenced the repeat distance of the model membrane based on CER[AP], and was not able to induce a phase separation in the investigated lipid matrix. However, a disorder and a fluidisation of the model membranes were observed when OA was incorporated. IPM showed the same effect but two phases (assigned as phase A and B) appeared, when IPM was used as penetration enhancer and incorporated into the model membrane. Furthermore, two arrangements of IPM were identified in phase A using deuterated IPM. A model of the nanostructure of the Stratum corneum lipid membranes is presented.

Here a case study of L-asparaginase II out of a recombinant Escherichia coli is presented. The target protein was obtained by simple cell disintegration and acetone precipitation. The L-asparaginase II has been crystallized in three different forms in the following microbatch crystallization. The rod-shaped crystals (~400 μm edge length) were obtained at either 8°C or 22°C after 17 h by addition of PEG₆₀₀₀. The rectangular-shaped crystals were obtained after further recrystallization of the rod-shaped crystals. The rhombic-shaped crystals formed at 8°C after 12 days when cold ethanol was used instead of PEG₆₀₀₀. All crystallizations were performed in tris-acetate buffer (50 mmol·L^-1, pH 5.1). By crystallization, the specific activity of L-asparaginase II has increased 5-fold. The protein content and the purity of the crystals were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The more concentrated L-asparaginase II out of an extract mixture and the presence of only less minor proteins after crystallization demonstrates that crystallization is an effective and mild method to purify the target protein. The single crystal X-ray diffraction pattern reveals that the crystals are proteins and the X-ray powder diffraction (XRPD) pattern shows clearly that the crystals forming in PEG₆₀₀₀ and ethanol have different crystal structures.

Emulsions and crystallization are two independent research topics which normally do not overlap although a combination of the two could be applicable to many areas. Here, the importance of emulsions in the field of fat crystallization is described. Three applications with industrial relevance were chosen for investigation: fat fractionation, the solidification of phase change materials and solid lipid nanoparticles. For fat fractionation and phase change materials, emulsification can be applied as a tool to improve the fat crystallization process, and thus the product quality of the crystallized fat. Furthermore, the use of emulsification creates new application fields such as solid lipid nanoparticles in the area of fat crystallization.

The crystal morphology grown from a solution composed of an organic solvent, solute and additive can be predicted reliably by a computational method. Modeling the supersaturated solution as liquid phase is achieved by employing commercial software. The molecular composition of this solution is a required input parameter. The face specific diffusion coefficient of the solid (crystal surface) and liquid (solution) system is determined using the molecular dynamics procedure. The obtained diffusion coefficient is related to the specific face growth rate via the attachment energy of the pure morphology. The significant improvements are achieved in the morphology prediction because the investigation on the face growth rates in a complex growth environment (as multi-component solutions with additives) can be carried out based on the diffusion coefficients.

Relationship between magnesium ammonium phosphate (MAP) crystal properties and the filtration ability of hollow fiber membrane (HFM) were investigated. Phosphorus recovery process by crystallization has a problem that it produces a large amount of fine crystals. So improvement of the crystallization process by combining with filtration was discussed. MAP crystals were obtained by batch reaction crystallization and the filtration characteristics were investigated. The filtration was evaluated by the specific filtration resistance (α_c) on HFM. Filtered slurry was prepared with each suspension density and crystal size distribution. The solution was filtered at constant pressure of 0.02 MPa and the filtration time on each filtrated volume was recorded. As a result, α_c decreases exponentially with suspension density increasing from 0.25 g/L to 0.5 g/L and α_c decreases moderately with suspension density increasing from 0.5 g/L to 1.5 g/L. α_c of large crystals decreases exponentially at less suspension density than α_c of small crystals does. Also, α_c increases as the ratio of the fractured crystals increases.

Au nanoparticles are expected for the media to transfer genes into plants. However, the control of particle size distribution (PSD) and shape of Au nanoparticles is too difficult to design and prepare particles with suitable quality for the gene supporting media. Reduction crystallization experiments were performed in aqueous solution in order to clarify the effect of feeding conditions such as feeding profile, feeding rate, and feeding amount on PSD and shape of Au nanoparticles. Ascorbic acid (AsA) was selected as a reducing agent because it is safe for plants. Au particles of 50 nm, 50–200 nm, and 150–400 nm were obtained in batch operation, single-jet, and double-jet, respectively. Moreover, in single-jet and double-jet, the mean size of the obtained Au particles increases with the decrease of feeding rate or the increase of feeding amount. It is concluded that PSD of Au nanoparticles can be controlled in the range of 50–400 nm by changing feeding conditions of AsA and HAuCl₄ aqueous solution.

In the dissolution step of spent nuclear fuel, there is a world-concern problem that zirconium molybdate hydrate precipitates as a byproduct, and accumulates in some reprocessing equipments. In order to prevent this accumulation, we have developed a new method based on the controlled reaction crystallization of zirconium molybdate hydrate (ZMH) in the reprocessing solution, followed by solid liquid separation. In order to measure the particle size of ZMH, batch crystallization experiments were conducted by varying nitric acid concentration and operating temperature. In result, almost all particle sizes scatter around 1 μm on average, despite the higher concentration of nitric aid and operating temperature, and then small particles grow up as an aggregate sticking to the crystallizer. Moreover, polymorph and color changing were observed by varying the concentration of nitric acid and reaction time. These results suggest that crystal color and adhesiveness are closely related to the particle size of ZMH. And the control of nitric acid concentration and small particle growth would be the useful technique to prevent the ZMH sticking.

In the present work, anti-solvent crystallization of artemisinin from four different organic solvents (methanol, ethanol, acetonitrile, and acetone) was studied. Water was used as anti-solvent. The effect of an impurity (quercetin) on the performance of anti-solvent crystallization of artemisinin was investigated. The fundamental process data such as solubility of artemisinin in pure organic solvents and their binary mixtures with varying composition water were measured at room temperature. The solubility of quercetin was measured only in pure organic solvents at room temperature. Anti-solvent crystallization experiments were designed based on the fundamental process data determined. Firstly, the anti-solvent crystallization of artemisinin without impurity was performed from all four organic solvents and then the experiments were repeated with addition of an impurity (quercetin) while keeping all other process parameters constant. Two different concentrations of impurity, i.e., 10% and 50% of its solubility, in the respective organic solvents at room temperature were used. The effect of impurity on performance of anti-solvent crystallization was evaluated by comparing the yield and purity of the artemisinin obtained with those in the absence of impurity. Results of the present work demonstrated that the presence of quercetin in the solution does not affect the final yield of artemisinin from the solution of each of four organic solvents used. However, the purity of artemisinin crystals were reduced when quercetin concentration was 50% of its solubility in all solvents studied.

Paracetamol (PCM) was crystallized from an isopropanol (IPA) solution containing various small amounts of metacetamol as an additive. The effect on the nucleation kinetics was studied by measuring the induction time to nucleation and the metastable zone width using focused beam reflectance measurements (FBRM) and attenuated total reflectance (ATR-UV/Vis) spectroscopy. Both the induction time and the metastable zone width were expressed as functions of the additive concentration. Small amounts of metacetamol (1–4 mol-%) were found to cause significant inhibition to the nucleation by extending both the induction time and the metastable zone width. A progressive change in the morphology of the paracetamol crystals from tabular to columnar habit was observed with increasing metacetamol concentration. The solvent also had a significant effect on the size of the paracetamol crystals as smaller crystals were obtained in IPA than in aqueous solution. The dissolution rate of paracetamol was improved by the incorporation of metacetamol with 4 mol-% having the most effect. A supersaturation control (SSC) approach was implemented for the PCM-IPA system with and without metacetamol in an attempt to control and obtain larger metacetamol-doped paracetamol crystals.

The effect of adding Co, Ni or La on the methanation activity of a Mo-based sulfur-resistant catalyst was investigated. As promoters, Co, Ni and La all improved the methanation activity of a 15% MoO₃/Al₂O₃ catalyst but to different extents. Similar improvements were also found when Co, Ni or La was added to a 15% MoO₃/25%-CeO₂-Al₂O₃ catalyst. The promotion effects of Co and Ni were better than that of La. However, the catalytic methanation activity deteriorated the most with time for the Ni-promoted catalyst. The used catalysts were analyzed by nitrogen adsorption measurement, X-ray diffraction and X-ray photoelectron spectroscopy.

The processing of molybdenum-uranium ore in a sulfuric acid solution using hydrogen peroxide as an oxidant has been investigated. The leaching temperature, hydrogen peroxide concentration, sulfuric acid concentration, leaching time, particle size, liquid-to-solid ratio and agitation speed all have significant effects on the process. The optimum process operating parameters were: temperature: 95°C; H₂O₂ concentration: 0.5 M; sulfuric acid concentration: 2.5 M; time: 2 h; particle size: 74 μm, liquid-to-solid ratio: 14 ∶ 1 and agitation speed: 600 rpm. Under these experimental conditions, the extraction efficiency of molybdenum was about 98.4%, and the uranium extraction efficiency was about 98.7%.

The leaching kinetics of molybdenum showed that the reaction rate of the leaching process is controlled by the chemical reaction at the particle surface. The leaching process follows the kinetic model 1 ? (1?X)^1/3 = kt with an apparent activation energy of 40.40 kJ/mole. The temperature, concentrations of H₂O₂ and H₂SO₄ and the mesh size are the main factors that influence the leaching rate. The reaction order in H₂SO₄ was 1.0012 and in H₂O₂ it was 1.2544.

A series of tensile and ratcheting experiments for compacted polytetrafluoroethylene (PTFE) and bronze filled PTFE (PTFE/bronze) were conducted on dynamic mechanical analyzer (DMA-Q800). The effects of mean stress, stress amplitude and temperature on the ratcheting behaviors of PTFE and PTFE/bronze were investigated. It is found that the stress-strain response of PTFE/bronze is nonlinear and its elastic modulus is higher than that of pure PTFE. For uniaxial ratcheting test, the dissipation strain energy density (DSED) decreases rapidly in the first 10 cycles and approaches a constant after 20 cycles. The ratcheting strain and the DSED corresponding to 100 cycles increase with increasing mean stress, stress amplitude and temperature. Additionally, the DSED and ratcheting strain of PTFE/bronze are much lower than those of pure PTFE under the same experimental conditions. It is also found that both pure PTFE and PTFE/bronze present cyclic hardening characteristics. Above all, the addition of bronze can improve both the uniaxial tensile property and the cyclic property of PTFE.

In this work, the enthalpy of fusion and melting points of 2-(tert-butyl)-5-methylphenol (2B5MP) and 2-(tert-butyl)-4-methylphenol (2B4MP) were measured by differential scanning calorimetry (DSC). The binary solid-liquid equilibrium (SLE) of both compounds were predicted by integrated computer aided system (ICAS) and measured by DSC. The corresponding eutectic molar composition is 0.6998 and the eutectic temperature is 281.96 K. The quasi-static heat capacities of 2B5MP and 2B4MP were evaluated by stochastic temperature modulation DSC technique (TOPEM). The SLE experimental data were correlated using the Margules, Wilson, and non-random two liquid (NRTL) equations and a good agreement between measurement and calculation could be obtained.

Polymethacrylic acid (PMA) was synthesized on the backbone of psyllium (Psy) by a microwave assisted method to prepare polymeric grafted materials designated as (Psy-g-PMA). Various grades of Psy-g-PMA were prepared by changing the degree of grafting from 35%–58% and the materials were then made into tablets. Swelling and biodegradability studies of the tablets were carried out. Acetyl salicylic acid was incorporated in the various Psy-g-PMA samples and tablets were prepared to study the in vitro drug release in acidic (pH= 4), neutral (pH= 7), and basic (pH= 9) media. In the acidic medium, the swelling was more than 1300%. In addition, the biodegradable Psy-g-PMA had the highest drug release in the acidic medium. This may be attributed to Fickian diffusion since the drug and the medium in which it was released have the same acidic nature.