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The appearance of a spurious double ITCZ south of the equator in coupled general circulation models has been a stubborn problem ever since the beginning of coupled model development. This article reviews the past research in this area, with a focus on three possible major contributors to the double ITCZ biases: 1) the southeastern Pacific marine stratus clouds and associated warm sea surface temperature (SST) biases; 2) the extratropical shortwave absorption biases over Southern Ocean; and 3) convective parameterization. The negative biases in marine boundary layer clouds in the southeastern Pacific lead to warm SST biases. Through coupled atmosphere-ocean interactions, it contributes to the double ITCZ bias. Positive shortwave absorption biases over Southern Ocean is believed to be an extratropical contributor to the double ITCZ biases in models. Since the heat from excess shortwave absorption must be transported to the northern hemisphere by the Hadley circulation, the position of the ITCZ must shift southward. However, later research finds that reducing the extratropical shortwave absorption has little effect on the ITCZ position. One possibility is that some feedback mechanism involving subtropical low-level clouds as intermediary is missing. For convective parameterization, changes in various elements in convection schemes can have large impacts on the ITCZ simulation. It involves a complex chain of interactions among convection, large-scale atmospheric circulation, SST, and upper ocean circulation. In one scheme, changes in the scheme lead to the elimination of double ITCZ in all seasons, giving hope that we can finally take on the double ITCZ problem.

This study investigates the influence of entrainment rate (λ) on relative dispersion (e) of cloud droplet size distributions (CDSD) in the 99 growing precipitating deep convective clouds during TOGA-COARE. The results show that entrainment suppresses e, which is opposite to the traditional understanding that entrainment-mixing broadens CDSD. To examine how the relationship between e and λ is affected by droplets with different sizes, CDSDs are divided into three portions with droplet radius

We investigated the polymorphic behaviors of empagliflozin (EMP), an SGLT2 inhibitor focusing on the preparation and characterization of its two distinct quasi-polymorphs combined with in-line monitoring of crystallization processes. EMP has only been reported as a single polymorph without pseudo-polymorphs so far. In this study, two differentiable crystal forms, the needle-shaped ‘Form I’ and platy-shaped ‘Form P’, were reproducibly created using an anti-solvent approach. Although the two forms of EMP yielded the same results in many of these analyses, they could be differentiated by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and microscopy. Based on a detailed analysis of DSC thermograms, a small but obvious transition was detected during the melting of crystalline EMP at 152–157 °C. This transition, which occurred at a low activation energy, was identified as a polymorphic transformation from Form P to Form I. The anti-solvent crystallization process was monitored by in-line NIR absorbance measurements and interpreted using principal component analysis (PCA). The crystal form was dependent on the crystallization solvent. Two different solvent/anti-solvent pairs (ethanol-water and ethanol-hexane) yielded substantially different PCA results, indicating distinct pathways to the creation of each crystal form. Rapid nucleation and high crystal growth rate was achieved by crystallization under Scheme P, which also exhibited fluctuation in its PC score plot. This was associated with reversible polymorphic selection between the two crystal forms during the crystallization of EMP.

The anti-solvent approach has been demonstrated as one potential industrial method to produce pharmaceutical co-crystal powders with high purity. In this study, we combined the anti-solvent method with cooling to maximize the yield of the solution-based co-crystallization between indomethacin (IMC) and saccharin (SAC). The cooling start time was the key process parameter; other parameters were fixed based on results of preliminary work. Highly pure IMC–SAC co-crystal powders were produced via the combined method, regardless of the cooling start time, and the yield was substantially enhanced. However, some material properties, such as crystallinity and particle size, were affected by the cooling start time; i.e., whether cooling was started before nucleation (pre-nucleation cooling) or after nucleation (post-nucleation cooling). When pre-nucleation cooling was applied, a greater degree of supersaturation led to nucleation of α-IMC and IMC–SAC together. The metastable α-IMC eventually transitioned to stable IMC–SAC co-crystal particles, followed by crystal growth. When post-nucleation cooling was applied, the transient α-IMC was not detected during the entire process.

The creation of co-crystals of various insoluble drug substances has been extensively investigated as a promising approach to improve their pharmaceutical performance. In this study, co-crystal powders of indomethacin and saccharin (IMC–SAC) were prepared by an anti-solvent (water) addition and compared with co-crystals by evaporation method. No successful synthesis of a pharmaceutical co-crystal powder via an anti-solvent approach has been reported. Among solvents examined, methanol was practically the only one that resulted in the formation of highly pure IMC–SAC co-crystal powders by anti-solvent approach. The mechanism of a preferential formation of IMC–SAC co-crystal to IMC was explained with two aspects: phase solubility diagram and solution complexation concept. Accordingly, the anti-solvent approach can be considered as a competitive route for producing pharmaceutical co-crystal powders with acceptable properties.

The co-crystal approach has been investigated extensively over the past decade as one of the most promising methods to enhance the dissolution properties of insoluble drug substances. Co-crystal powders are typically produced by mechanical grinding (neat or wet) or a solution method (evaporation or cooling). In this study, high-purity carbamazepine-saccharin (CBZ-SAC) co-crystals were manufactured by a novel method, anti-solvent addition. Among various solvents, methanol was found to perform well with water as the anti-solvent for the co-crystallization of CBZ and SAC. When water was added to the methanol solution of CBZ and SAC at room temperature under agitation, nucleation of CBZ-SAC co-crystals occurred within 2-3 min. Co-crystallization was complete after 30 min, giving a solid yield as high as 84.5% on a CBZ basis. The effects of initial concentrations, focusing on the SAC/CBZ ratio, were examined to establish optimal conditions. The whole anti-solvent co-crystallization process was monitored at-line via ATR-FTIR analysis of regularly sampled solutions. The nucleation and crystal growth of CBZ-SAC co-crystals were detected by a significant increase in absorption in the range of 2400-2260 cm(-1), associated with the formation of hydrogen bonds between the carbonyl group in CBZ and the N-H of SAC. When CBZ hydrates were formed as impurities during anti-solvent co-crystallization, the hydrogen bonding between methanol and water was reduced greatly, primarily due to the incorporation of water molecules into the CBZ crystal lattice. In conclusion, an anti-solvent approach can be used to produce highly pure CBZ-SAC co-crystal powders with a high solid yield.

The in-line monitoring of pharmaceutical processes with high risk, such as crystallization, has been one of the most popular research topics in recent years. Sulfamerazine (SMZ), a well-known sulfonamide antibacterial agent was investigated to examine the mechanism of polymorphic conversion by solvent-mediated polymorphic transformation (SMPT). The primary purpose of this study is to monitor the polymorphic transformation through in-line near-infrared (NIR) measurements and concurrently interpret the whole process quantitatively with off-line characterizations. Samples taken at every hour during SMPT were analyzed by X-ray diffractometry (XRD) and differential scanning calorimetry (DSC). NIR spectra in the range of 7500–4900 cm−1 were taken into account for multivariate analysis, which included partial least square (PLS) regression and principal component analysis (PCA). In brief, the form II content was estimated very accurately and reproducibly during the SMPT process not only by XRD but also by the DSC measurements. In addition, the form II content values were predicted very accurately by separate experiments at two designated time points. In a separate study, it was demonstrated that PCA could be employed to explain a complicated process such as SMPT mechanistically by several stages

Along with the risk-based approach, process analytical technology (PAT) has emerged as one of the key elements to fully implement QbD (quality-by-design). Near-infrared (NIR) spectroscopy has been extensively applied as an in-line/on-line analytical tool in biomedical and chemical industries. In this study, the film thickness on pharmaceutical pellets was examined for quantification using in-line NIR spectroscopy during a fluid-bed coating process. A precise monitoring of coating thickness and its prediction with a suitable control strategy is crucial to the quality assurance of solid dosage forms including dissolution characteristics. Pellets of a test formulation were manufactured and coated in a fluid-bed by spraying a hydroxypropyl methylcellulose (HPMC) coating solution. NIR spectra were acquired via a fiber-optic probe during the coating process, followed by multivariate analysis utilizing partial least squares (PLS) calibration models. The actual coating thickness of pellets was measured by two separate methods, confocal laser scanning microscopy (CLSM) and laser diffraction particle size analysis (LD-PSA). Both characterization methods gave superb correlation results, and all determination coefficient (R(2)) values exceeded 0.995. In addition, a prediction coating experiment for 70min demonstrated that the end-point can be accurately designated via NIR in-line monitoring with appropriate calibration models. In conclusion, our approach combining in-line NIR monitoring with CLSM and LD-PSA can be applied as an effective PAT tool for fluid-bed pellet coating processes.

Microwave-assisted hydrothermal reaction to prepare barium titanate (BaTiO3) particles using titanium acylate precursors was investigated. Experimental variables taken into account in this study were the reaction type (reflux and autoclave), the reaction time and the Ba to Ti ratio in sol solutions. Autoclave reactions were more effective than reflux reactions in terms of time and barium utilization efficiency. In both type reactions, the variation in Ba to Ti ratio in sol solutions led to substantial changes in particle morphology as well as Ba:Ti stoichiometry in resulting particles. Mechanisms for those changes were proposed. Characterization of synthesized particles were performed via SEM, XRD, Raman, XPS and elemental analysis based on ICP.

The adhesion characteristics of Cu films grown on Si and TiN substrates by PECVD were studied. Cu(etac) 2 was used as metalorganic precursor. The adhesion strength of Cu films was measured by the peel test in accordance with ASTM B 571-91. The adhesion strength of Cu films before 450 °C treatment was 13–27 kg f /cm. The oxidation of substrates before deposition showed a negative effect on the adhesion of Cu films. The adhesion was substantially improved by thermal treatment at 450 °C. The adhesion improvement by 450 °C treatment was mainly attributed to the removal of tensile residual stress in Cu films.

Continuous silicon carbide fibers (UF fibers) with low oxygen content (∼1−2 wt%) were prepared in a range of diameters (∼8−50 μm) by the dry spinning of organosilicon polymer solutions and subsequent pyrolysis of the polymer fibers. Room-temperature mechanical properties were similar to commercially-available Nicalon TM fibers, as average tensile strengths ≈3 GPa were obtained for some batches with fiber diameters in the range of ∼10 μm. Furthermore, UF fibers showed significantly better thermomechanical stability compared to Nicalon, as indicated by lower weight losses, lower specific surface areas, and improved strength retention after heat treatment at temperatures up to 1700°C. The structure and composition of UF fibers were also characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Auger depth profiling analysis, neutron activation analysis, and atomic absorption.