Apparent Dissolution Research Articles

Equilibrium Solubility of Sulfadiazine in (Acetonitrile + Ethanol) Mixtures: Determination, Correlation, Dissolution Thermodynamics, and Preferential Solvation

The equilibrium solubility of sulfadiazine (SD, 3) in several {acetonitrile (MeCN) + ethanol (EtOH)} mixtures at nine temperatures from T/K = (278.15 K to 318.15) has been determined by following the shake flask method. SD solubility increased with temperature-arising as well as with the MeCN proportion-increasing in the mixtures. Thus, x3 increased from 7.74 × 10−5 in neat EtOH to 6.20 × 10−4 in neat MeCN at T/K = 298.15. SD solubility was adequately correlated with a second-order multivariate equation as function of both mixtures composition and temperature. Moreover, two models including the Jouyban–Acree and Jouyban–Acree–van’t Hoff models were applied to mathematical SD solubility data modeling in solvent mixtures. The accuracy of each model is investigated by the mean relative deviations (MRD%) of the back-calculated solubility. A full predictive model was provided by training the Jouyban–Acree–van’t Hoff model with only seven experimental solubility data which provided excellent predictions with the MRD% of 3.7 %. All used models show a low MRD% values (< 4.0 %) for the calculated data indicating a good correlation of SD solubility data with the given mathematical models. By means of the van’t Hoff and Gibbs equations, the apparent thermodynamic quantities relative to SD dissolution and mixing processes, namely Gibbs energies, enthalpies, and entropies, were calculated and reported. Apparent dissolution quantities of SD were positive in all cases indicating endothermic and entropy-driven behaviors. A non-linear enthalpy–entropy relationship was observed for SD in the plot of SD dissolution enthalpy vs. Gibbs energy. Observed trend exhibits negative slope in the composition from neat EtOH to the mixture of 0.05 in mass fraction of MeCN indicating entropy-driving mechanism for this SD transfer process. Moreover, variant but positive slopes were found in the composition interval of 0.05 < w1 < 1.00 indicating enthalpy-driving mechanism for these SD transfer processes. Furthermore, the preferential solvation of SD by MeCN or EtOH was analyzed by using the inverse Kirkwood–Buff integrals. Thus, SD is preferentially solvated by EtOH molecules in EtOH-rich mixtures but preferentially solvated by MeCN in MeCN-rich mixtures. In this way, this research expands the literature investigations about the solubility of SD in some non-aqueous cosolvent mixtures conformed by MeCN and other alcohols.

Effects of fluid salinity and composition on subcritical crack growth in marble

Subcritical fracture growth of rocks in fluid-chemical environments played a crucial role in the weathering process of rocks and the preservation of stone building heritage. Fracture mechanics properties of marble under different fluid compositions and salinity conditions were investigated by carrying out double torsion tests. The subcritical crack growth index (SCI) exhibited different salinity dependencies in two salt solutions. In NaCl solution, the SCI decreased by 1.97 % – 40.50 % with increasing salinity due to the increase in solubility of calcite. The SCI decreased by 4.60 % and 14.01 % respectively as the Na2SO4 salinity increases from 0.01 mol/L to 1 mol/L, and then increased with the increase in salinity, which was related to the relationship between calcite solubility and salinity. Compared to Na2SO4 solution, the weakening effect of NaCl solution on Ka was smaller. In contrast, the fracture toughness (KIC) was insensitive to fluid composition and salinity in the short term, with KIC ranging from 0.65 to 0.79 MPa m1/2 in all salt solutions. The three-dimensional morphology results of the fracture surfaces indicated that the effect of salinity on the roughness of both fracture types was negligible. However, the microstructure of the marble was significantly affected by salinity, and apparent dissolution was observed. The results highlighted the dependence of the subcritical fracture behavior of marble on fluid chemistry, which had implications for the weathering assessment of stone masonry buildings and the permanent protection of stone heritage monuments. In these applications, fluid chemistry could either strengthen or weaken the rock, depending on variations in fluid composition and salinity.

N-Heterocyclic carbene-based gold etchants.

N-Heterocyclic carbenes (NHCs) are an emerging alternative to thiols for the formation of stable self-assembled monolayers (SAMs) on gold. We examined several different species that have been used to produce NHC-based monolayers on gold, namely 1,3-diisopropyl-5-nitrobenzimidazolium iodide, 1,3-diisopropyl-5-nitrobenzimidazolium hydrogen carbonate, bis(1,3-diisopropyl-5-nitrobenzimidazolium)gold(I) iodide, and 1,3-diisopropyl-5-nitrobenzimidazole-2-ylidene. Contrary to expectation, solutions containing the first two species in tetrahydrofuran and dichloromethane caused visible loss of gold from thin-film-coated glass slides. The use of toluene solutions of all species resulted in no apparent dissolution of gold. We present scanning electron micrographs and elemental imaging analyses by energy dispersive X-ray spectroscopy to examine the effect of solutions of each species on the gold film. This work highlights the risk of unwanted etching during some routes to NHC-based surface functionalization but also the potential for deliberate etching, with the outcome determined by choice of chemically synthesized organic species and solvent.

Isotonic, aqueous-based media as simple and suitable test media for short-term Haemonchus placei adult worm motility assay

The solvating power of test media used in anthelmintic assays is critical to the validity of assay results, especially when evaluating plant extracts. High solutes in media lowers its solvating power, altering the range of concentrations available for investigation and assay performance. To identify simplified, well-tolerated media for adult Haemonchus placei with improved solvating power, we investigated the impact of varying solutions of pH (2.5–8.5), salinity (19–154 mM), and normal saline (NS) incorporating dissolution enhancers (acetone, propylene glycol, DMSO and Tween-80; 10–40% v/v) on the nematode over 3 h at room temperature. The performance of identified media, NS and 20% Tween-80 in NS, were evaluated by preparing sample extracts (acetone extract Sarcocephalus latifolius, AESL20&10; and chloroform extract Vernonia amygdalina, CEVA20&10) stock solutions (20 and 10 mg/mL) in them, assessed their apparent dissolution, and each highest stock solution that dissolves the extracts evaluated for anthelmintic activity against H. placei. We found isotonicity to be the critical-to-worm survival factor as H. placei survived 100% in pH solutions 3.5–8.5, and saline solutions 39–154 mM. The dissolution enhancers, at 40%, gave no survival. At 30% and 20%, only Tween-80 gave 92.5% and 100% survival, respectively. At 10%, Tween-80, acetone, DMSO and propylene glycol gave 100%, 100%, 87.5% and 0% survival, respectively. In 20% Tween-80 in NS, AESL20&10 and CEVA20&10 dissolved, furnishing wider concentration range (20-0 mg/mL); whereas only AESL10 dissolved in NS (narrower concentration range, 10-0 mg/mL). The LC50s (mg/mL) of 7.67 (AESL10, NS) and 7.48 (AESL20, Tween-80 in NS) were not significantly different (p > 0.05), while CEVA20 (Tween-80 in NS) gave 2.67. Our findings show that NS and 20% Tween-80 in NS, as isotonic, aqueous-based media, are suitable, and well-tolerated as test media for adult H. placei in a short-term motility assay. Up to 30% Tween-80 could be used to enhance dissolution where necessary.

Solid-liquid equilibrium and dissolution thermodynamic properties of L-isoleucine in binary solvent mixtures

Thermodynamic properties, which play an important role in design and optimization of crystallization processes, are the essential data for the study of crystal nucleation and growth. In this study, the solubility of L-isoleucine were firstly determined by gravimetric method in three binary solvent mixtures including water + (ethanol, acetonitrile or DMSO) in the temperature range of 303.20 K to 338.05 K at atmospheric pressure. The effects of temperatures and solvent types on the dissolution process of L-isoleucine were investigated. It was found that the solubility of L-isoleucine increased dramatically with the increasing of the mole fraction of water in each binary solvent mixture and increased monotonically with the increasing of temperature. To extend the applicability of the solubility data, the experimental solubility data of L-isoleucine were fitted and analyzed using the modified Apelblat equation, the CNIBS/R-K model and the Jouyban-Acree model. Finally, based on the Van’t Hoff equation and the experimental solubility data, the apparent dissolution thermodynamic properties of L-isoleucine including apparent dissolution enthalpy, apparent dissolution entropy, and apparent Gibbs free energy change of dissolution process were calculated and discussed.

Impact of Crystal Nuclei on Dissolution of Amorphous Drugs.

Amorphous drugs are used to improve bioavailability of poorly water-soluble drugs. Crystallization must be managed to take full advantage of this formulation strategy. Crystallization of amorphous drugs proceeds in a sequence of crystal nucleation and growth, with different kinetics. At low temperatures, crystal nucleation is fast, but crystal growth is slow. Therefore, amorphous drugs may generate dense but nanoscale crystal nuclei. Such tiny nuclei cannot be detected using routine powder X-ray diffraction (PXRD) and polarized light microscopy (PLM). However, they may negate the dissolution advantage of amorphous drugs. In this work, for the first time, the impact of crystal nuclei on dissolution of amorphous drugs was studied by monitoring the real-time dissolution from amorphous drug films, with and without crystal nuclei, and the evolving crystallinity in the films. Three model drugs (ritonavir/RTV, posaconazole/POS, and nifedipine/NIF) were chosen to represent different crystallization tendencies in the supercooled liquid state, namely, slow-nucleation-and-slow-growth (SN-SG), fast-nucleation-and-slow-growth (FN-SG), and fast-nucleation-and-fast-growth (FN-FG), respectively. We find that although the amorphous films containing nuclei do not show obvious differences from the nuclei-free films under PLM and PXRD before dissolution, they have inferior dissolution performance relative to the nuclei-free amorphous films. For SN-SG drug RTV, crystal nuclei have negligible impact on the crystallization of amorphous films, dissolution rate, and supersaturation achieved. However, they cause earlier de-supersaturation by inducing crystallization in solution as heterogeneous seeds. For FN-SG drug POS and FN-FG drug NIF, crystal nuclei accelerate crystallization in the amorphous films leading to lower supersaturation achieved with POS, and elimination of any supersaturation with NIF. Dissolution profiles of amorphous films can be further analyzed using a derivative function of the apparent dissolution rate, which yields amorphous solubility, initial intrinsic dissolution rate, and onset of crystallization in the amorphous films. This study highlights that although crystal nuclei are undetectable with routine analytical methods, they can significantly negate, or even eliminate, the dissolution advantage of amorphous drugs. Hence, understanding crystal nucleation process and developing approaches to prevent it are necessary to fully realize the benefits of amorphous solids.

Experimental study on plagioclase dissolution rates at conditions relevant to mineral carbonation of seafloor basalts

Over the last two decades, all scenarios projected to achieve the goals of the Paris climate agreements have required negative emissions of greenhouse gases. Mineral carbonation of basalt is a promising negative emission technology for long-term storage of carbon dioxide (CO2). During mineral carbonation, dissolved CO2 is converted into solid carbonate minerals through reaction with silicate minerals. Plagioclase feldspars are the most abundant primary silicate minerals in basalts readily available for water-rock interactions. Despite numerous recent laboratory studies, the rate at which plagioclase dissolution occurs under the required conditions for large-scale carbon storage remain poorly constrained. In this study, we present new flow-through experiments quantifying the apparent dissolution rates of plagioclase in sodium chloride solutions with elevated concentrations of dissolved CO2 at temperatures between 25 °C and 125 °C and pressure of 200 bars. The mildly acidic conditions produced by carbonic acid yield apparent rates that are slower than those previously reported for plagioclase under more acidic conditions and alkaline conditions. We used these apparent rates to develop new temperature-dependent rate equations for plagioclase dissolution in solutions buffered by carbonic acid:kCa=10−9.811±0.664exp−22.27±2.08R∙1T−1TrkSi=10−10.334±0.445exp−33.99±1.40R∙1T−1Trwhere k is the rate constant (mol m−2 s−1) at any temperature (T in K), R is the universal gas constant (8.3145 KJ/mol/K)and Tr is the reference temperature (298.15 K). Utilizing the new Ca rate equation into a geochemical model, we estimated that the reaction time to achieve carbonate saturation in a closed system with high CO2 ranges from a few days to a few years depending on water-to-mineral ratios. These results could have significant implications for required monitoring on projects or achieving gigaton-scale of carbon storage and mineralization annually, where planned injection rates of million(s) of tons of CO2 per well per year could overwhelm aquifer alkalinity, lower pH, and reduce the efficiency of carbon mineralization.

Effect of mono, di, tri ethanolamine lactate ionic liquids on the solubility of acetaminophen: Experimental measurement and correlation

Solubility is one of the most important physicochemical properties in the discovery and development of drugs and adding a co-solvent to an aqueous solution for further designing drug formation is the most widely used method in the pharmaceutical industry. In recent years, protic ionic liquids (PILs) as a new low-cost and an environmentally friendly class of green solvents have been used to overcome drug solubility issues. In this research work, the effect of some PILs containing 2-hydroxyethylammonium, bis(2-hydroxyethyl)ammonium, and tris(2-hydroxyethyl)ammonium cations and lactate anion have been investigated for acetaminophen (ACP) solubility at temperature ranges (298.15 to 313.15) K. The results show that ACP solubility increases with increasing PIL concentration and at higher temperatures and that PILs containing tris(2-hydroxyethyl)ammonium lactate have a greater impact on ACP solubility. The obtained solubility data were fitted by the e-NRTL and Wilson models which e-NRTL model is more consistent with experimental data. Finally, by applying the Gibbs and van't Hoff equations, the apparent dissolution thermodynamic functions such as enthalpy, Gibbs free energy, and entropy have been estimated. The results indicate that ACP dissolution processes in the investigated systems are endothermic.

A Geo‐Structurally Based Correction Factor for Apparent Dissolution Rates in Fractured Media

AbstractField measurements of apparent geochemical weathering reaction rates in subsurface fractured porous media are known to deviate from laboratory measurements by multiple orders of magnitude. To date, there is no geologically based explanation for this discrepancy that can be used to predict reaction rates in field systems. Proposed correction factors are typically based on ad hoc characterizations related to geochemical kinetic models. Through a series of high‐fidelity reactive transport simulations of mineral dissolution within explicit 3D discrete fracture networks, we are able to link the geo‐structural attributes with reactive transport observations. We develop a correction factor to linear transition state theory for the prediction of the apparent dissolution rate based on measurable geological properties. The modified rate law shows excellent agreement with numerical simulations, indicating that geological structure could be a primary reason for the discrepancy between laboratory and field observations of apparent dissolution rates in fractured media.

Dissolution mechanism of alumina inclusions into CaO–SiO 2 –Al 2 O 3 –Fe t O–MgO slag via a converter tapping process

Reducing the amount of inclusions during the steelmaking process as much as possible and much earlier plays a vital role in improving the quality of steel products. To reveal the dissolution mechanism of inclusions in slag during the converter tapping process, some comparison experiments were conducted by adding isolated spherical alumina balls as inclusions in CaO–SiO2–Al2O3–FetO–MgO slag, and FetO content up to 10% was contained in slag. The results showed that the dissolution rate of alumina balls in the slag was mainly affected by the diffusion of Al2O3, and the diffusion coefficients of Al2O3 were 4.2 × 10–11, 7.5 × 10–11, and 1.5 × 10–10 m2/s at 1500℃, 1550℃, and 1600℃, respectively. In addition, the upgraded diffusion-distance-controlled dissolution model (DDD-Model), in which FetO content was introduced and applied in the study. The results illustrated that the Al2O3 inclusion apparent dissolution rate was improved by a high FetO content, increasing CaO/SiO2 and raising the temperature as soon as possible at the early stage of the converter tapping process. It is not necessary to increase the FetO content in the slag to enhance the dissolution rate of the Al2O3 inclusion at the last tapping stage. The predicted complete dissolution time of spherical Al2O3 inclusions with 1000 µm in diameter based on the upgraded DDD-Model was approximately 1796 s during the actual converter tapping process.

RNA is required for the integrity of multiple nuclear and cytoplasmic membrane‐less RNP granules

Numerous membrane‐less organelles, composed of a combination of RNA and proteins, are observed in the nucleus and cytoplasm of eukaryotic cells. These RNP granules include stress granules (SGs), processing bodies (PBs), Cajal bodies, and nuclear speckles. An unresolved question is how frequently RNA molecules are required for the integrity of RNP granules in either the nucleus or cytosol. To address this issue, we degraded intracellular RNA in either the cytosol or the nucleus by the activation of RNase L and examined the impact of RNA loss on several RNP granules. We find the majority of RNP granules, including SGs, Cajal bodies, nuclear speckles, and the nucleolus, are altered by the degradation of their RNA components. In contrast, PBs and super‐enhancer complexes were largely not affected by RNA degradation in their respective compartments. RNA degradation overall led to the apparent dissolution of some membrane‐less organelles, whereas others reorganized into structures with altered morphology. These findings highlight a critical and widespread role of RNA in the organization of several RNP granules.

Solubility, solvent effect, enthalpy–entropy compensation and solvation thermodynamics of 4-(bromomethyl)-2(1H)-quinolinone in several aqueous blends

The current study was mainly devoted to solubility for the systems formed by 4-(bromomethyl)-2(1H)-quinolinone (BMQ) and blended solvents of isopropanol, N-methyl-2-pyrrolidinone (NMP), ethanol and n-propanol with water. Experiments for solubility determination were conducted by employing the shake-flask equilibration method from 278.15 to 318.15 K under 101.2 kPa. For each aqueous cosolvent mixture, the minimum solubility was recorded in water at 278.15 K; and the maximum value, in neat organic solvents at 318.15 K. The solubility performance was illustrated by Hansen solubility parameters of water, BMQ and co-solvents. No occurrence of polymorphic transformation or solvation was observed after experiments based on the XRD spectra of raw BMQ and excess solids analyzed. The satisfactory correlation results for solubility data was obtained by modified Wilson model, mixture response surface model, modified van’t Hoff-Jouyban–Acree model and Jouyban–Acree model. The relative average deviations were calculated to be no more than 8.72 %. Investigation on the relative contributions from inter- and intra-molecular interactions to the solubility variation of BMQ at temperature of 298.15 K was quantitatively performed via the linear solvation energy relationships (LSER). The descriptors of solvent blends including solubility parameter, dipolarity-polarizability and hydrogen-bond basicity were primarily responsible for the solubility variation. As well, the preferential solvation of BMQ was researched quantitatively via the inverse Kirkwood–Buff integrals method on the basis of some obtainable properties of solvent blends. The positive preferential solvation parameters for BMQ in middle and cosolvent-rich blends strongly suggest that the crystalline solute of BMQ is preferentially solvated by cosolvents of isopropanol, NMP, ethanol and n-propanol. The transfer and apparent dissolution properties including apparent Gibbs energy change (298.15 K), dissolution enthalpy and dissolution entropy (298.15 K) were derived and discussed. Analysis of enthalpy–entropy compensation indicates the entropy-driven mechanism of BMQ dissolved in all blend solvents.

The co-solvency and thermodynamic properties calculation of flunarizine hydrochloride in mixtures of (acetonitrile/ethyl acetate + isopropanol)

The solubility of flunarizine hydrochloride was improved by co-solvent in this work. In (acetonitrile + isopropanol) and (ethyl acetate + isopropanol) binary mixtures, it was measured at the temperature range from T = (273.15 To 313.15) K by the isothermal equilibrium method under 101.3 kPa. The solubility values in two mixtures increased firstly and then decreased with the increasing mass fraction of acetonitrile or ethyl acetate, and reached the maximum when the mass fraction of acetonitrile (w) = 0.60, and ethyl acetate (w) = 0.40 at all investigated temperatures. In pure solvents, the largest solubility is obtained in isopropanol, followed by acetonitrile and ethyl acetate. In mixture of (acetonitrile + isopropanol), the maximum and minimum values at 298.15 K are 5.98 × 10−3 and 2.91 × 10−3, respectively, and 5.91 × 10−3 and 2.24 × 10−3 in mixture of (ethyl acetate + isopropanol). The Jouyban-Acree model and CNIBS/R-K model were used to evaluate the results. Moreover, the relative contributions of solvent–solvent and solute–solvent interactions on the drug solubility variation were studied via the analysis of linear solvation energy relationships. The maximum value of relative average deviation (RAD) of Jouyban-Acree model was 4.20% in mixture of (acetonitrile + isopropanol), and for CNIBS/R-K model, it was 5.34% at 298.15 K in mixture of (acetonitrile + isopropanol). All values of apparent dissolution standard enthalpy (ΔHsolo), apparent molar standard Gibbs energy (ΔGsolo) and apparent dissolution standard entropy (ΔSsolo) are positive, which indicates the dissolution process is endothermic and entropy-increasing. The results of the relative contributions by enthalpy (ζH) and by entropy (ζTS) toward to Gibbs energy of the solution process show that the enthalpy is the main contributor to standard free energy of solution process.

Rapid Elemental Extraction from Ordered and Disordered Solutes by Acoustically-Stimulated Dissolution

Alkaline industrial wastes (e.g., slags: ordered crystalline solids, and fly ashes: disordered solids) represent abundant reservoirs of elements such as silicon and calcium. Rapid elemental extractions from these wastes, however, have often relied on the use of “stoichiometric additives” (i.e., acids or bases). Herein, we demonstrate that acoustic stimulation enhances the release of network-forming Si species from crystalline blast furnace slags and amorphous fly ashes at reaction temperatures less than 65 °C. These additive-free enhancements are induced by cavitation processes which reduce the apparent activation energy of solute dissolution (Ea, kJ/mol) by up to 40% as compared to unstimulated conditions. Because of the reduction in the apparent activation energy, acoustic stimulation features an energy intensity that is up to 80% lower in promoting dissolution, as compared to other additive-free methods such as enhancing the solute’s surface area, introducing heat, or convectively mixing the solvent. Based on atomic topology analysis, we show that the reduction in apparent dissolution activation energy upon acoustic stimulation scales with the number of weak topological constraints per atom in the atomic network of the dissolving solute, independent of their ordered or disordered nature. This suggests that sonication breaks the weakest constraints in the solute’s atomic network, which, in turn, facilitates dissolution. The results suggest the ability of acoustic stimulation to enhance waste utilization and circularity, by enabling efficient resource extraction from industrial wastes.

The co-solvency and thermodynamic properties of camptothecin in mixtures of (ethyl acetate + methanol/ethanol)

The solubility profile, molecular interactions and apparent dissolution thermodynamic properties of camptothecin in mixtures of (ethyl acetate + methanol) and (ethyl acetate + ethanol) was studied at the temperature range from T = (273.15 to 318.15) K under 101.3 kPa. In two mixtures, the solubility profile increased firstly and then decreased with the increasing mass fraction of ethyl acetate. In mixture of (ethyl acetate + methanol) at 318.15 K, it reached a maximum (9.176 × 10-5) in mole fraction when the mass fraction of ethyl acetate (w) = 0.80, and 7.554 × 10-5 in mixture of (ethyl acetate + ethanol) at w = 0.60. The Jouyban-Acree model and CNIBS/R-K model were applied to evaluate the solubility profile. The relative average deviation (RAD) data of Jouyban-Acree model in mixture of (ethyl acetate + methanol) was 3.81%, and 5.50% in mixture of (ethyl acetate + ethanol). However, it was no more than 3.59% for CNIBS/R-K model. The CNIBS/R-K model was more consistent than Jouyban-Acree model. In addition, the KAT-LSER model was used to analyse the effect of the solute–solvent intermolecular interactions on solubility profile. Furthermore, apparent dissolution thermodynamic analysis of camptothecin in mixtures of (ethyl acetate + methanol) and (ethyl acetate + ethanol) at the mean harmonic temperature was also performed. The results indicated that the dissolution process was endothermic and entropy-increasing, and the enthalpy is the main contributor to standard free energy of solution process.

Reduced deliquescency of isosorbide by cocrystallization and mechanisms for hygroscopicity

Isosorbide (ISO) is an effective hyperosmotic agent that can be administrated orally and is used as a therapeutic agent for brain pressure drop, glaucoma, and Meniere’s disease. However, the critical relative humidity (CRH) of ISO is about 48% RH at 25 °C, and it deliquesces in humid environments. In this study, we attempted to reduce the deliquescence of ISO using cocrystallization and analyze the water adsorption mechanism from the crystal structure. Four new ISO cocrystals with piperazine (PZ), hydrochlorothiazide (HCT), 3,5-dihydroxybenzoic acid (35DHBA), or gallic acid (GA) were identified. The dynamic vapor sorption analyses demonstrated that all the cocrystals showed higher CRHs than the ISO crystal. Although water adsorption below the CRH was observed for all cocrystals, the water molecules adsorbed in the ISO-PZ and ISO-GA cocrystals were lower than those in the ISO crystal. Investigation of the crystal structures suggested that the amount of water adsorbed might be related to the degree of exposure of the ISO hydroxyl groups on the crystal surface. Given the CRH, water adsorption below the CRH, thermal stability, apparent dissolution rate, and toxicity level of the coformer, the ISO-GA cocrystal is the most suitable for preparing a solid formulation of ISO.

Investigation on the Solubility of the Antidepressant Drug Escitalopram in Subcritical Water

Escitalopram (ESC), the S-enantiomer of citalopram, is a selective serotonin reuptake inhibitor. Escitalopram is widely used to treat panic disorder, depression, obsessive compulsive disorder, and social anxiety disorder. The main goal of this present research is to determine the aqueous solubility of ESC at temperatures ranging from 298 to 473 K and a pressure of 5.0 MPa. ESC solubility increased significantly from 1.08 × 10–3 to 59.88 × 10–3 (mole fraction) when the temperature was raised from 298 to 473 K. This is a 55-fold enhancement. A mathematical model was developed based on our experimental solubility data. The model was used to successfully predict the solubility of ESC in subcritical water. Furthermore, experimental data were correlated using a modified Apelblat equation. The apparent thermodynamic analysis including apparent dissolution standard enthalpy (ΔsolH) and apparent dissolution standard entropy (ΔsolS) were calculated. Thermodynamic property calculations showed that the process is endothermic ΔsolH > 0, and the ΔsolS values were relatively high. Spectroscopic analyses revealed that ESC was stable in subcritical water at temperatures up to 473 K. The enhanced solubility of ESC in subcritical water enabled us to use high-temperature liquid chromatography to separate this antidepressant drug.

Evaluating agronomic soil phosphorus tests for soils amended with struvite

Struvite is an emerging, recycled phosphorus (P) fertilizer of low water solubility (<5%). As a first step towards wide-scale integration of struvite into agricultural systems, distinct interpretation of soil test phosphorus (STP) values for soils amended with struvite may be needed due to the persistence of struvite for months after its application (i.e., residual struvite). However, STP methods were developed for soils amended with highly water-soluble P fertilizers and may not necessarily translate to soils with residual struvite prior to soil testing for P recommendation. We evaluated the potential effects of STP method and edaphic properties (pH, clay content) on STP values for soils with residual struvite. To mimic residual struvite, struvite granules were added to a quartz control and to six soils encompassing a range of pH (4.3, 6.0, 8.1) representative of agricultural soils and with contrasting clay content. The mixtures were then extracted by common STP methods (Mehlich-3, Bray-1, Olsen), Resin, and Haney 3A-2. In the quartz control, dissolution of struvite granules in STP extraction solutions ranged from 59% in Resin to 10% in H3A-2. In soil treatments, apparent dissolution of struvite among STP methods was 19–401% higher for acidic soils with low versus high clay contents. Adsorption experiments confirmed that the disparity in the apparent dissolution of struvite in soils was caused by adsorption of dissolved P on clay minerals. Additionally, for acidic soils with high clay content, scanning electron microscopy coupled with energy dispersive X-ray spectroscopy identified surface deposition of Al and Si on the struvite granule surface during STP extractions, which may have decreased struvite dissolution. Depending on STP method, residual struvite dissolution may overestimate STP concentrations by 20–3900%. Results demonstrate the need to account for the impacts of residual struvite on measured STP values. As a next step, quantifying in situ struvite dissolution rates across soil and cropping conditions is needed to evaluate the extent to which residual struvite may require adjustment of yield-based calibration of STP values.

Equilibrium solubility of edaravone in some binary aqueous and non-aqueous solutions reconsidered: Extended Hildebrand solubility approach, transfer property and preferential solvation

The accessible equilibrium solubility data of edaravone in methanol/ethanol/isopropanol (1) + water (2) and ethyl acetate/acetonitrile (1) + methanol/ethanol/n-propanol (2) mixtures was investigated in terms of solvent–solute molecule interactions based on extended Hildebrand solubility method. For methanol (1) + water (2) with x1 (mole fraction) from 0 to 0.8, ethanol (1) + water (2) with x1 from 0 to 0.5 and isopropanol (1) + water (2) with x1 from 0 to 0.3, the interaction energies of solute-solvent molecules were greater than the geometric average values of regular solution, specifying some association between edaravone and mixed solvents. While in the other regions for the three aqueous solutions and ethyl acetate/acetonitrile + methanol/ethanol/n-propanol mixtures, edaravone solutions acted as regular ones at several points. A quartic expression of energy term W in terms of solvent solubility parameter of these mixtures could be successfully used to predict the equilibrium solubility of edaravone in the studied blended mixtures. The preferential solvation of edaravone by means of inverse Kirkwood–Buff integrals tool for the isopropanol/ethanol/methanol + water and ethyl acetate + n-propanol/methanol/ethanol mixtures was analyzed. For the isopropanol/ethanol/methanol + water blended solvents, the drug edaravone was surrounded preferentially by water in water-rich ranges, and by alcohols in other composition regions of binary blended solvents except for isopropanol solutions with isopropanol-rich compositions, where edaravone was preferentially solvated by water. As well, edaravone was preferentially solvated by ethanol for ethyl acetate + ethanol mixture with rich ethyl acetate compositions. The highest degree of preferential solvation was observed in aqueous isopropanol solutions. Selective solvation of the edaravone by water (isopropanol/ethanol/methanol + water mixtures) or ethanol (ethyl acetate + ethanol mixture) was attributable to greater acidity of water or ethanol that enabled interactions with Lewis basic groups of edaravone. In addition, the apparent dissolution enthalpy and transfer Gibbs free energy (ΔtrGo), transfer enthalpy (ΔtrHo) and transfer entropy (ΔtrSo) were derived and deeply discussed.

Combined Effect of the Preparation Method and Compression on the Physical Stability and Dissolution Behavior of Melt-Quenched Amorphous Celecoxib.

In an earlier investigation, amorphous celecoxib was shown to be sensitive to compression-induced destabilization. This was established by evaluating the physical stability of uncompressed/compressed phases in the supercooled state (Be̅rziņš . Mol. Pharmaceutics, 2019, 16(8), 3678-3686). In this study, we investigated the ramifications of compression-induced destabilization in the glassy state as well as the impact of compression on the dissolution behavior. Slow and fast melt-quenched celecoxib disks were compressed with a range of compression pressures (125-500 MPa) and dwell times (0-60 s). These were then monitored for crystallization using low-frequency Raman spectroscopy when kept under dry (∼20 °C; <5% RH) and humid (∼20 °C; 97% RH) storage conditions. Faster crystallization was observed from the samples, which were compressed using more severe compression parameters. Furthermore, crystallization was also affected by the cooling rate used to form the amorphous phases; slow melt-quenched samples exhibited higher sensitivity to compression-induced destabilization. The behavior of the melt-quench disks, subjected to different compression conditions, was continuously monitored during dissolution using low-frequency Raman and UV/vis for the solid-state form and dissolution properties, respectively. Surprisingly the compressed samples exhibited higher apparent dissolution (i.e., higher area under the dissolution curve and initial celecoxib concentration in solution) than the uncompressed samples; however, this is attributed to biaxial fracturing throughout the compressed compacts yielding a greater effective surface area. Differences between the slow and fast melt quenched samples showed some trends similar to those observed for their storage stability.