Showing papers by "Baohong Hou published in 2016"

Effects of solvent and supersaturation on crystal morphology of cefaclor dihydrate: a combined experimental and computer simulation study

Abstract: The modified attachment energy model was employed to predict cefaclor dihydrate morphology Meanwhile, the mechanism and the effect of solvent and supersaturation on the crystal morphology were also proposed A molecular dynamics simulation was applied to investigate the interactions of cefaclor dihydrate crystal faces with the pure solvent model and the solution model The mechanism of solvent effects on the different faces was elaborated by discussing the surface structure and the adsorption of the crystal, while the effect of supersaturation was considered from the aspect of molecular recognition The radial distribution function analysis was introduced to explore the adsorption behaviors of solvent and solute molecules From the mean square displacement of solvent and solute molecules, the growth shape was affected by the solvent and solute diffusion capacity The results suggested that the morphology evolution is due to the subtle competition of the molecular adsorptions between the solute and solvent

Process Design for Antisolvent Crystallization of Erythromycin Ethylsuccinate in Oiling-out System

Abstract: The crystallization process of erythromycin ethylsuccinate in a tetrahydrofuran–water system was investigated. Results show that oiling-out occurs under several conditions; hence, a phase diagram with a liquid–liquid equilibrium area was established experimentally. For improved understanding of oiling-out crystallization, a series of in situ tools, including focused beam reflectance measurement, attenuated total reflectance Fourier transform infrared spectroscopy, and particle vision measurement, were applied to monitor the oiling-out phenomenon and the subsequent nucleation of erythromycin ethylsuccinate. SEM images were employed to analyze the influence of oiling-out on the properties of the final crystals. The nucleation mechanism of erythromycin ethylsuccinate differs significantly depending on the location of the line of operation. The combination of cooling method and antisolvent crystallization can be achieved with fundamental data of the phase diagram to suppress the oiling-out phenomenon and obta...

Oiling out and Polymorphism Control of Pyraclostrobin in Cooling Crystallization

Abstract: In this study, phase diagrams of form II (metastable form) of pyraclostrobin under different cooling rates were measured with the aid of in situ tools such as ATR-FTIR, FBRM, and PVM. It was found that the initial concentration of pyraclostrobin corresponding to the metastable state critical oiling out point upon cooling decreases with the increase of cooling rate. Meanwhile, the seeding strategy experiments illuminated that seed loading and seed size are important factors to avoid the oiling out and to obtain form IV (stable form) of pyraclostrobin. By optimizing the cooling rate and employing the seeding strategy, oiling out could be eliminated and products of pure form IV of pyraclostrobin could be obtained.

Measurement of Solubility of Thiamine Hydrochloride Hemihydrate in Three Binary Solvents and Mixing Properties of Solutions

Abstract: Data on (solid + liquid) equilibrium of thiamine hydrochloride hemihydrate (HH) in {water + (ethanol, acetone, or 2-propanol)} solvents will provide essential support for industrial design and further theoretical studies. In this study the solid–liquid equilibrium (SLE) was experimentally measured over temperatures ranging from 278.15 to 313.15 K under atmospheric pressure by a dynamic method. For the temperature range investigated, the equilibrium solubility of thiamine hydrochloride hemihydrate (HH) varies with temperature and the composition of the solvents. The experimental solubility was regressed with different models including the modified Apelblat equation, λh equation, as well as NRTL equation. All the models gave good agreements with the experimental results. On the basis of the solubility data of HH, the thermodynamic properties of mixing process of HH with mixed solvents were also discussed. The results indicate that the mixing process of HH is exothermic. Besides, the model outwardly like the...

Antisolvent Crystallization of Erythromycin Ethylsuccinate in the Presence of Liquid–Liquid Phase Separation

Abstract: The nucleation point of erythromycin ethylsuccinate crystallization with liquid–liquid phase separation, also called oiling-out, was determined through nucleation analysis. To achieve successful monitoring of nucleation events, focused beam reflectance measurements were performed during antisolvent crystallization. The induction time of the oiling-out system was determined and correlated with classical nucleation theory. The induction time increases with decreasing solubility under a constant thermodynamic driving force. The position of a nucleation point may be determined by comparing the nucleation energy barrier and supersaturation generated in solute-rich and solute-lean phases. The estimated interfacial energy is in the range of 0.422–1.315 m·J/m2, which is in agreement with nucleation theory. A homogeneous nucleation process was observed under high supersaturation, and heterogeneous nucleation took place at low supersaturation. The growth mechanism was identified with the interfacial tension. The co...

Crystal structure, thermal crystal form transformation, desolvation process and desolvation kinetics of two novel solvates of ciclesonide

Abstract: Two novel solvates of ciclesonide were successfully obtained and characterized by various analytical techniques (X-ray powder diffraction, X-ray single-crystal diffraction, differential scanning calorimetry, thermogravimetric analysis and hot-stage microscopy). Crystal structure analysis results indicate that the solvate of ciclesonide formed with cyclohexane (HCC) is a channel solvate and isostructural with ciclesonide, while the solvate formed with methanol (MC) isa discrete position solvate. Thermal analysis results show that HCC could desolvate without destroying the crystal lattice. However, MC would transform into an amorphous form after desolvation and the amorphous form could recrystallize into the crystalline form of ciclesonide. Moreover, the kinetics of the HCC and MC isothermal and non-isothermal desolvation processes is calculated and discussed.

Solvent penetration mediated phase transformation for the preparation of aggregated particles with well-defined shape

Abstract: We report here a unique method for the preparation of aggregated crystals with well-defined shape and size using a solvent penetration-mediated phase transformation. An unusually fast phase transformation of sulfadiazine was observed. The aggregated sulfadiazine crystals are obtained through a water penetration mediated transformation of sulfadiazine N-methyl pyrrolidone solvate. The aggregated particles keep the same shape and size of the parent crystals.

Formation and Transformation Behavior of Sodium Dehydroacetate Hydrates

Abstract: The effect of various controlling factors on the polymorphic outcome of sodium dehydroacetate crystallization was investigated in this study. Cooling crystallization experiments of sodium dehydroacetate in water were conducted at different concentrations. The results revealed that the rate of supersaturation generation played a key role in the formation of the hydrates. At a high supersaturation generation rate, a new sodium dehydroacetate dihydrate needle form was obtained; on the contrary, a sodium dehydroacetate plate monohydrate was formed at a low supersaturation generation rate. Furthermore, the characterization and transformation behavior of these two hydrated forms were investigated with the combined use of microscopy, powder X-ray diffraction (PXRD), Raman spectroscopy, Fourier transform infrared (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and dynamic vapor sorption (DVS). It was found that the new needle crystals were dihydrated and hollow, and they eventually transformed into sodium dehydroacetate monohydrate. In addition, the mechanism of formation of sodium dehydroacetate hydrates was discussed, and a process growth model of hollow crystals in cooling crystallization was proposed.

Thermodynamics of 1,3-Dimethylurea in Eight Alcohols

Abstract: In this work, solubility data of 1,3-dimethylurea (DMU) in methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, and 1-octanol were measured by synthetic method from T = 288.15 to 328.15 K at ordinary pressure. It turned out that the solubility data increased as temperature and solvent polarity increased. The molecular interactions in solution have been studied by the linear energy relationship. Furthermore, based on two thermodynamic models (i.e., modified Apelblat and Wilson), the experimental results were fitted and analyzed. Finally, the thermodynamic properties of solution, including entropy, enthalpy, and Gibbs energy were calculated. These results indicate that in all selected solvents the dissolution behavior were endothermic, entropy-driven, and not spontaneous.

Argatroban novel crystal and preparation method thereof

Abstract: The invention relates to an argatroban novel crystal and a preparation method thereof, wherein the novel crystal has characteristic peaks shown by X-ray powder diffraction 2 theta: 4.0+/-0.1, 6.9+/-0.1, 7.9+/-0.1, 9.6+/-0.1, 10.1+/-0.1, 13.6+/-0.1, 15.0+/-0.1, 17.1+/-0.1, 19.8+/-0.1, 21.1+/-0.1, 23.6+/-0.1 and 29.9+/-0.1. The preparation method comprises the steps: dissolving an argatroban crude product in a solvent isopropyl alcohol to obtain a solution with the solution concentration of 0.09-0.3 g/mL, heating to 30-50 DEG C, stirring to dissolve, clarifying, dropwise adding anti-solvent water to the solution, then cooling to 5-15 DEG C, keeping constant temperature for 2-4 h, filtering a crystal slurry, washing, drying, and thus obtaining the argatroban novel crystal-form crystal. The R/S ratio of the obtained product is in a range of (57-67):(43-33) specified in Chinese pharmacopoeia, and the product has pharmacological activities. The yield is 91-94%, the HPLC detection purity is 99.9%, and the product has good stability. The crystal has a shape of stick, the surface is smooth, the edge is regular, and the product has no coalescence.

Omeprazole sodium semihydrate and preparation and preparation method thereof

Abstract: Disclosed are an omeprazole sodium semihydrate and a preparation method therefor. One mole of omeprazole sodium semihydrate contains 0.5 mole of water, and the X-ray diffraction spectrum thereof has characteristic peaks at diffraction angles 2θ of 6.26±0.1, 11.10±0.1, 12.20±0.1, 15.58±0.1, 16.02±0.1, 17.12±0.1, 19.08±0.1, 21.00±0.1, 22.68±0.1, 23.48±0.1, 24.08±0.1, 26.52±0.1 and 28.08±0.1 degrees. The omeprazole sodium semihydrate is obtained by adding a raw material omeprazole sodium hydrate into an organic solvent, stirring same for 2-9 hours at a constant temperature of 25°C-60°C, and then filtering and drying same. The omeprazole sodium semihydrate of the present invention is high in purity, good in stability, will not easily agglomerate, and has good flowability, and has broader application prospects.