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Solubility is recognised as one of the most important physicochemical parameters necessary for a successful clinical candidate. Despite that, there are few articles in the medicinal chemistry literature with a specific focus on so...
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Solubility is recognised as one of the most important physicochemical parameters necessary for a successful clinical candidate. Despite that, there are few articles in the medicinal chemistry literature with a specific focus on solubility-driven optimisation of lead compounds. This could be because the importance of measuring solubilities as part of the optimisation process is relatively underappreciated, or the fact that obtaining sufficient high quality solubility data is difficult. This review gives examples of solubility-driven optimisation programs from the last fifteen years, and explores recent developments in solubility measurement techniques. Quantitative NMR methods are highlighted; these offer the potential to provide high quality solubility measurements in a cost-effective and high-throughput manner. (C) 2016 Elsevier Ltd. All rights reserved.
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A rapid gravimetric method for determining drug candidate solubility in organic solvents has been developed. The scale, speed, precision, and accuracy of the method make it ideal for solubility screening of pharmaceutical compound...
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A rapid gravimetric method for determining drug candidate solubility in organic solvents has been developed. The scale, speed, precision, and accuracy of the method make it ideal for solubility screening of pharmaceutical compounds during early development. The method utilizes a thermogravimetric analyzer to automate drying and weighing. Results for model compounds compare favorably with literature values.
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The solubility of molybdenite, MoS_2, in fluid-saturated, subaluminous to peraluminous granitic melts was determined experimentally using rapid-quench cold-seal pressure vessels at 800 ℃ and 100-200 MPa, and analysis by laser-abl...
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The solubility of molybdenite, MoS_2, in fluid-saturated, subaluminous to peraluminous granitic melts was determined experimentally using rapid-quench cold-seal pressure vessels at 800 ℃ and 100-200 MPa, and analysis by laser-ablation ICP-MS. Molybdenite solubility seems to be independent of pressure, but it shows strong variations with oxygen and sulfur fugacity. At constant log fS_2 = -1.3 it increases from 0.1-0.7 ppm by weight Mo at the Co-CoO buffer to 29-38 ppm by weight Mo near the MnO-Mn_3O_4 buffer. The solubility isopleths are nearly parallel to the pyrrhotite-magnetite equilibrium, along which the solubility varies only slightly, from 10 ppmw Mo at the quartz-fayalite-magnetite buffer to 29-38 ppmw Mo at the MnO-Mn_3O_4 buffer. The observed solubility variations are consistent with the equilibrium MoS_2(s) + 3/2O_2 = MoO_3 (l) + S_2 and thus confirm that molybdenum(VI) oxide is the predominant species in subaluminous silicate melts at log fO_2 = -16 to -11. In addition, the experimental results are well reproduced by a simple thermodynamic model employing the Burnham eight-oxygen formulation for silicate melt species and assuming ideal mixing of dissolved MoO_3. The thermodynamic calibration can be used to estimate the molybdenum solubility in subaluminous silicic melts or, for pyrrhotite- and molybdenite-saturated assemblages, the oxygen and sulfur fugacities during magma crystallization.
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The polythermal solubility of C60 and fullerene mixture (60% C60, 39% C70, and 1% C76–90) in butyric and enanthic acids was studied over the temperature range 20–80°C. The corresponding solubility polytherms are given and characterized.
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A mechanistic approach to identify the driving force for crystallization and to determine the solubility of solids crystallized from solutions containing multiple conformers is presented. It is assumed that only one conformer, whi...
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A mechanistic approach to identify the driving force for crystallization and to determine the solubility of solids crystallized from solutions containing multiple conformers is presented. It is assumed that only one conformer, which is referred to as the right conformer (RC), integrates into the crystal surface if the energy barrier of transition between conformers is higher than 10kcal/mol. Conformers that do not integrate into the crystal surface are lumped into a single conformation which is referred to as the wrong conformer (WC). This approach, which is referred to as the approach of the RC, was applied to two organic substances that presented unusual solubility and crystallization behaviors: constant or retrograde solubility and sharply decreasing crystallization duration with temperature. For both substances, ~1H NMR data indicated the presence of multiple conformations in solution and rotomers' peak coalescence was reached at relatively high temperature indicating high energy barriers of transition between conformers. In addition, ab initio calculations revealed that the RC is the high energy conformer indicating that the WC levels in solution are higher. On the basis of these observations, the approach of the RC was considered to be applicable for the substances studied. This approach considers that the RC is the only species in true equilibrium with the solid at saturation. The intrinsic solubility and the total solubility are introduced for non-ionizable organic molecules and are defined respectively as the concentration of the RC and the concentration of all conformers at saturation. The intrinsic supersaturation (ISS), defined as the concentration of the RC minus the intrinsic solubility, is considered to be the driving force for the crystallization and expressions relating the total solubility and the ISS to crystallization parameters are derived. Computed total solubility was in agreement with either the constant or retrograde solubility observed experimentally for the substances studied. Slow crystallization was attributed to the low levels of the calculated ISS and to crystal growth inhibition caused by high levels of the WC. In addition, this approach provided a simple means for the experimental estimation of the energy difference between the two main conformers. Finally, on the basis of the predicted increase of ISS with temperature, an alternate crystallization procedure based on a single heating ramp was utilized to provide crystals with improved powder properties.
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The solubility graph gamma S(G) associated with a finite group G is a simple graph whose vertices are the elements of G, and there is an edge between two distinct vertices if and only if they generate a soluble subgroup. In this p...
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The solubility graph gamma S(G) associated with a finite group G is a simple graph whose vertices are the elements of G, and there is an edge between two distinct vertices if and only if they generate a soluble subgroup. In this paper, we focus on the set of neighbors of a vertex x which we call the solubilizer of x in G, SolG(x), investigating both arithmetic and structural properties of this set.
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One of the main factors defining intestinal drug absorption is the solubility of the compound in the gastrointestinal environment. This study reports the solubility of a series of 27 commonly used acidic, neutral and basic drugs i...
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One of the main factors defining intestinal drug absorption is the solubility of the compound in the gastrointestinal environment. This study reports the solubility of a series of 27 commonly used acidic, neutral and basic drugs in human intestinal fluid samples collected from the duodenum or jejunum of healthy volunteers under fasted state conditions. The interindividual variability as well as the impact of factors such as pH, sampling site and bile salts on the solubility in human intestinal fluids was investigated. The solubility measurements were evaluated using a statistical experimental design. Variability in solubility across volunteers and sampling sites was highly compound-specific and appeared to be substantial for weak acids and bases and for lipophilic drugs. Both pH of the samples and the abundance of amphiphilic components were responsible for the variability observed in the solubility values obtained. The results confirm strong interindividual differences in intraluminal solubility, especially for compounds with high lipophilicity and/or compounds with a pKa value within the physiological pH range. It is important to recognize this variability in intestinal drug solubility as it may considerably influence the therapeutic outcome among patients. (C) 2017 Elsevier B.V. All rights reserved.
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Although plant-based proteins potentially provide merits for long-term global food security, their poor functionality particularly solubility has hampered the utilization as functional biopolymers in the industry. High intensity u...
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Although plant-based proteins potentially provide merits for long-term global food security, their poor functionality particularly solubility has hampered the utilization as functional biopolymers in the industry. High intensity ultrasound (HIUS, 20 kHz) has been researched extensively for its possible application in modifications of protein functionality. Here, we show that the solubility of commercial pea protein isolate (PPI) is drastically improved from 7.2 to 58.4 mg/mL at an intermediate power (150 W) after a sequential HIUS treatment with an elevated power (100, 150, 200, 300, and 400 W). The dynamic changes of protein structure and confirmation over the course of sequential HIUS treatment are comprehensively investigated. This allows us to address the knowledge gap among the extensively studied power of HIUS and the structure changes of pea protein. Quantifying nonproteinaceous constituents (dietary fiber and beta-glucan) and observing the morphological changes of the resultant pea protein solution have served as a critical step toward understanding the mechanism of action of HIUS in improving protein solubility. These successive investigation unravels that the formation of soluble aggregates between pea proteins and soluble complex between pea protein and indigenous dietary fiber is the underlying reason that HIUS improves the solubility of poorly soluble pea protein. Our findings offer unprecedented insights into the fundamental role of HIUS on structure modification of plant protein, thus paving the way for their industrial applications as green technique in fabricating plant proteins with improved solubility.
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The existence of soluble materials is on of the effective parameters in choosing the type and site of the dams. Thus understanding the behavior and mechanism of such materials against different environmental terms as surface and c...
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The existence of soluble materials is on of the effective parameters in choosing the type and site of the dams. Thus understanding the behavior and mechanism of such materials against different environmental terms as surface and cortical currents andthe effect of minerals in water like salts and their effects on soluble materials are necessary. In this paper, solubility tests on samples with gypsum from Marash dam site for different salt percentages have been done. The results sfibw that with the increase of salt and flow rate, the solubility rate increases. With an increase in temperature the gypsum solubility rate increases. In addition, the results indicate that the saturation time for water-soluble gypsum with different rates is less than the results of soluble tests with sodium chloride.
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The solubility behaviour of baicalin in individual solvents ranging from non-polar to highly polar solvents was evaluated and the results were analyzed in the light of existing systems of data analysis with reference to solubility...
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The solubility behaviour of baicalin in individual solvents ranging from non-polar to highly polar solvents was evaluated and the results were analyzed in the light of existing systems of data analysis with reference to solubility parameters. Hildbrand approach, extended Hansen's approach, four solubility parameters approach were used to analyze the solubility data and obtain partial solubility parameters of baicalin. Flory-Huggin's size connection term 'B' was found to further improve the value of regression equations. The solubility behaviour regression equations of baicalin were obtained by different approaches, such as ideal solubility model and non-ideal solubility model by Hildbrand solubiliy approach, activity coefficient and T3' models by extended Hansen's approach and four dimensional solubility parameters approach respectively. The total solubility parameter of baicalin may be in the range of 27.79-33.29 (J/cm~3)~(1/2). Different approaches were used in fitting the experimental solubility data to obtain regression equations which aim to provide a reasonable prediction of solubility of baicalin in untested solvents based on the theory of solubility parameters.
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