Baohong Hou

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

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.

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

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.

Formation and Transformation Behavior of Sodium Dehydroacetate Hydrates

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.

In Situ Monitoring and Modeling of the Solution-Mediated Polymorphic Transformation of Rifampicin: From Form II to Form I

In this article, the solution-mediated polymorphic transformation of rifampicin was investigated and simulated in 3 solvents at 30°C. The solid-state form I and form II of rifampicin was characterized by powder X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, Raman spectroscopy, and Fourier transform infrared spectroscopy (FTIR). To explore the relative stability, solubility data of form I and form II of rifampicin in butan-1-ol were determined using a dynamical method. In addition, Raman spectroscopy and focused beam reflectance measurement were used to in situ monitor the transformation of rifampicin from form II to form I. The liquid state concentration of rifampicin was measured by UV spectroscopic method. To investigate the effect of solvent on transformation, the transformation experiments were carried out in 3 solvents. Furthermore, a mathematical model was built to describe the kinetics of dissolution, nucleation, and growth processes during transformation by using experimental data. By combination of experimental and simulation results, it was found that the transformation process of rifampicin is controlled by dissolution of form II in heptane, whereas the transformation in hexane and octane was firstly controlled by dissolution of solid-state form and then controlled by growth of form I.

Effects of Hydrogen Bond Acceptor Ability of Solvents on Molecular Self-Assembly of Sulfadiazine Solvates

The solvate formation of sulfadiazine (SDZ) was systematically studied in the 4 selected solvents with the aids of experiment and simulation methods. The intermolecular interactions between solute and solvent molecules in different solid states were analyzed and compared through their single crystal structures, and the solution behavior of SDZ was discussed using molecular dynamics simulations. The results indicated that SDZ was easy to form solvates with the solvents having strong hydrogen bond acceptor ability, which determined the formation of hydrogen bonding synthon. Furthermore, the SDZ molecules conformation and packing were compared in various crystal structures. In addition, the desolvation processes of SDZ solvates were studied to investigate the role of solvent in different solvate structures.

Revealing the Roles of Solvation in D-mannitol’s Polymorphic Nucleation

There has been much interest in the role of solution chemistry in determining the polymorphic formation of organic crystals. For convenience, the predominantly investigated systems are those that contain distinct building blocks among the polymorphs; in this work, an important drug excipient, D-mannitol (D-man), was selected as a case study, which represents a polymorphic system that only has the same building blocks. By employing the Hirshfeld surface analysis and molecular dynamics (MD) simulations, D-mans crystal packing and the solvation nature in different solvents were studied on the molecular level. The results suggest that there is a direct link between the solution speciation and crystal structure, and two distinct solvation modes were identified along with their impacts on nucleation. This study indicates the significant role of solvation in determining D-mans nucleation and offers new insights into the research on systems that do not have distinct building blocks among the polymorphs.

Progress in membrane distillation crystallization: Process models, crystallization control and innovative applications

Membrane distillation crystallization (MDC) is a promising hybrid separation process that has been applied to seawater desalination, brine treatment and wastewater recovery. In recent years, great progress has been made in MDC technologies including the promotion of nucleation and better control of crystallization and crystal size distribution. These advances are useful for the accurate control of the degree of supersaturation and for the control of the nucleation kinetic processes. This review focuses on the development of MDC process models and on crystallization control strategies. In addition, the most important innovative applications of MDC in the last five years in crystal engineering and pharmaceutical manufacturing are summarized.