The use of aminoglycoside antibiotics is limited by ototoxicity that can produce permanent hearing loss. We report that concurrent administration of N-methyl-D-aspartate (NMDA) antagonists markedly attenuates both the hearing loss and destruction of cochlear hair cells in guinea pigs treated with aminoglycoside antibiotics. These findings indicate that aminoglycoside-induced hearing loss is mediated, in part, through an excitotoxic process. The high correlation (Spearman correlation coefficient: 0.928; P < 0.01) obtained between the relative cochleotoxicities of a series of aminoglycosides in humans and the potencies of these compounds to produce a polyamine-like enhancement of [3H]dizocilpine binding to NMDA receptors is consistent with this hypothesis, and provides a simple in vitro assay that can predict this aspect of aminoglycoside-induced ototoxicity.

High-pressure methane sorption isotherms were collected on selected Paleozoic shales from the Sichuan Basin. Excess sorption measurements were performed on shales with varied water content (dry, moisture equilibrated at 33%, 53%, 75%, and 97% relative humidities) at 39 °C and up to 25 MPa. Water uptake isotherms were collected at 24 °C and parametrized by the Guggenheim–Anderson–de Boer (GAB) model. The effect of organic richness, mineral compositions, and pore structure characteristics on water uptake and methane sorption behavior has been investigated. The mechanism responsible for the decrease in methane sorption capacity of moisture-equilibrated shales is discussed. Water uptake of shales is primarily controlled by clay minerals, and shows a positive correlation with clay mineral content. Water sorption isotherms of shales can be approximately expressed as the sum of the isotherms of individual clay minerals on a mass-fraction base. Methane sorption capacity of these shales is controlled by TOC content. The maximum Langmuir sorption capacity of shales under both dry and 97% RH conditions correlates positively with TOC content. Compared to dry conditions, methane sorption capacity of shales moisture-equilibrated at 97% RH is reduced by 44% to 63%. The experimental results indicate a stepwise decline in methane sorption with increasing water content. Evolution of sorption capacity as a function of water content can be divided into three stages: (1) initial decline stage where the decrease of methane sorption capacity is mainly due to competitive sorption of methane and water on hydrophilic clay minerals; (2) steep decline stage where clusters of water molecules block pore space and reduce the sorption capacity significantly; and (3) slow decline stage, where a contiguous water phase successively fills the macropores and slightly reduces methane sorption by volume displacement.

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In situ Raman spectroscopy was applied for the analysis of the solution-mediated polymorphic transformation of prasugrel hydrochloride from the metastable form II to the stable form I. The solution concentration during the transition process was monitored by a gravimetric method. The main factors studied were solvent, temperature, solid loading, and agitation speed. Because of the balance between the solubility and the strength of solute−solvent interactions, the transformation rate was highest in ethyl acetate and lowest in butanone at all three temperatures studied (20, 30, and 40 °C). The thermodynamic driving force of the polymorphic transformation from form II to form I was evaluated through solubility measurements of the two forms in ethyl acetate, acetone, and butanone. At increasing temperature, the nucleation induction time and the overall transformation time decreased despite the decreasing driving force. The solid loading seemed to have no effect on the transformation time because of surface nucleation of form I on form II, as determined from the morphology−time profile through polarizing microscope analysis, whereas increasing the agitation rate resulted in a faster polymorphic transformation process. It was confirmed by transformation experiments that the polymorphic transformation from form II to form I is controlled by the nucleation and growth of the stable form I crystal.

The crystallization process of vanillin in a 1-propanol/water system was investigated. It was found that liquid− liquid phase separation, also termed oiling out, will happen under some conditions. To fully understand this process, the oiling out as well as the following nucleation and crystal growth of this compound were investigated by using series of in situ tools such as FBRM, ATR-FTIR, and PVM. The phase diagram, including the solubility curve and the liquid−liquid separation curves, was determined experimentally. Meanwhile, the influence of oiling out on the properties of the final crystalline product was analyzed. It was proposed that crystallization mechanisms of vanillin might be significantly different depending on the position of the crystallization profile in the phase diagram. By using the fundamental data of phase diagram, control and optimization of solution crystallization of vanillin could be achieved to avoid or suppress the oiling out and to get products with high purity and ideal crystalline properties.

Three intrinsic properties of solvent were used to evaluate the effects of solvent on polymorph formation of prasugrel hydrochloride. In situ Raman spectroscopy, FTIR, and powder X-ray diffraction were used to characterize two solvent-free polymorphs and five solvates of prasugrel hydrochloride, the two of which were reported for the first time. Reactive crystallization in 24 different pure solvents was studied at 313.15 K. It was found that polymorph formation of prasugrel hydrochloride directly depends on the solvents used in the experiments. Form I was obtained in solvents with low values of hydrogen bond donor ability (HBD), while form II was obtained in solvents with high values of HBD. The thermodynamic and kinetic reasons for the solvent effects were explained by using the solubility data and the nucleation experiments. The solubilities of forms I and II were experimentally determined by a gravimetric method, and an equation based on the linear free energy approach for predicting solubility was applied to correlate the solubility of form II. It was found that the values of HBD of the solvents also affect the solubility of prasugrel hydrochloride. From desolvation experiments of the five solvates in seven pure solvents at 293.15 and 313.15 K, it was found that the polymorphs of prasugrel hydrochloride obtained after desolvation are closely related to the solvents. The heterogeneous nucleation of form I during the solvent-mediated polymorphic transformation was also studied at 313.15 K, and it was found that the solute–solvent interactions will also affect the nucleation rate of form I. A hypothesis was then proposed that prasugrel hydrochloride form I is prone to crystallize when van der Waals force dominates the interaction between the solute and the solvent molecules, while prasugrel hydrochloride form II is prone to nucleate and grow when hydrogen bonding dominates the interaction between the solute and the solvent molecules.

The solubilities of the homologous series of dicarboxylic acids, HOOC−(CH 2 ) n−2 −COOH (n = 2−10), in water have been measured at temperatures ranging from 288.15 to 323.15 K by a static analytic method at atmospheric pressure. Dicarboxylic acids with even numbers of carbon atoms exhibit lower solubilities than acids with adjacent odd carbon numbers. The odd−even effect of solubility is most likely associated with the twist of the molecules, which influences the molecular packing in the solid state: the molecules stack with some offset in the cases of even (n = even) series, but without offset in the cases of odd (n = odd) series, whereas the carboxyl groups are twisted in even members. The interlayer packing is looser in odd members than that in even ones. The energies of intramolecular torsion were calculated using Materials studio 6.0 (Accelrys Software Inc.). Finally, the molar Gibbs energies were predicted, which also showed odd−even alternation.

Screening of suitable coformers is a major challenge during the development of cocrystals. To guide and simplify the cocrystal synthesis process, we evaluated three different predictive methods as well as their combinations during the cocrystallization of 2-amino-4,6-dimethoxypyrimidine (MOP) with 63 components. The conductor-like screening model for the real solvents (COSMO-RS) approach offered the best predictive results among three methods with an overall success rate of 84.1%. When combined with molecular complementarity (MC) analysis, the success rate was up to 85.7%. The Hansen solubility parameters (HSP) method did not deliver a satisfying outcome no matter if used individually or in combination for the MOP system. In addition, based on the screened results, 21 new solid phases of MOP were experimentally observed. Among them, the crystal structures of 10 multicomponent crystals (cocrystals and salts) were revealed by single crystal X-ray diffraction analysis (SCXRD), and their thermodynamic and spectroscopy properties were also characterized. The Hirshfeld surface analysis and the molecular electrostatic potential (MEP) surface analysis were conducted to explore the interactions in multicomponent crystals and the origin for salts and cocrystals. The cases in this study not only enriched the solid forms of MOP, evidenced the feasibility of the combined screening method, but also set an effective example for choosing potential coformers to prepare multicomponent crystals.