Experimental Dissolution Rates Research Articles

A Novel Drug-Drug Salt of Naproxen and Vortioxetine: Synthesis, Characterization, and Solubility Study

Naproxen (NAP) is an aromatic propionic acid nonsteroidal anti-inflammatory drug, and vortioxetine (VOT) is a novel antidepressant drug. In this study, a new 1 : 1 drug-drug salt of NAP and VOT (namely, NAP-VOT) was designed and synthesized by liquid-assisted grinding and slow evaporation. The obtained salt was characterized by single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Single-crystal structure showed that NAP-VOT is a molecular salt. The NAP and VOT molecules in the salt were connected by N-H+⋯O hydrogen bonds between the carbonyl oxygen of NAP and the piperazine group of VOT. In addition, solubility and dissolution rate experiments were performed in water and pH 6.86 phosphate buffers, and the result suggested that salt formation could increase the solubility and dissolution rate of NAP and VOT in water. Furthermore, this study provides a new research idea to solve the problem of drug-drug combination by achieving drug-drug association at the molecular level.

Particle Size-dependent Dissolution of Uranium Aerosols in Simulated Lung Fluid: A Case Study in a Nuclear Fuel Fabrication Plant.

Inhalation exposure to uranium aerosols can be a concern in nuclear fuel fabrication. The ICRP provides default absorption parameters for various uranium compounds but also recommends determination of material-specific absorption parameters to improve dose calculations for individuals exposed to airborne radioactivity. Aerosol particle size influences internal dosimetry calculations in two potentially significant ways: the efficiency of particle deposition in the various regions of the respiratory tract is dependent on aerodynamic particle size, and the dissolution rate of deposited materials can vary according to particle size, shape, and porosity because smaller particles tend to have higher surface-to-volume ratios than larger particles. However, the ICRP model assumes that deposited particles of a given material dissolve at the same rate regardless of size and that uptake to blood of dissolved material normally occurs instantaneously in all parts of the lung (except the anterior portion of the nasal region, where zero absorption is assumed). In the present work, the effect of particle size on dissolution in simulated lung fluid was studied for uranium aerosols collected at the plant, and its influence on internal dosimetry calculations was evaluated. Size fractionated uranium aerosols were sampled at a nuclear fuel fabrication plant using portable cascade impactors. Absorption parameters, describing dissolution of material according to the ICRP Human Respiratory Tract Model, were determined in vitro for different size fractions using simulated lung fluid. Samples were collected at 16 time-points over a 100-d period. Uranium content of samples was determined using inductively coupled plasma mass spectrometry and alpha spectrometry. In addition, supplementary experiments to study the effect of pH drift and uranium adsorption on filter holders were conducted as they could potentially influence the derived absorption parameters. The undissolved fraction over time was observed to vary with impaction stage cut-point at the four main workshops at the plant. A larger fraction of the particle activity tended to dissolve for small cut-points, but exceptions were noted. Absorption parameters (rapid fraction, rapid rate, and slow rate), derived from the undissolved fraction over time, were generally in fair agreement with the ICRP default recommendations for uranium compounds. Differences in absorption parameters were noted across the four main workshops at the plant (i.e., where the aerosol characteristics are expected to vary). The pelletizing workshop was associated with the most insoluble material and the conversion workshop with the most soluble material. The correlation between derived lung absorption parameters and aerodynamic particle size (impactor stage cut-point) was weak. For example, the mean absorption parameters derived from impaction stages with low (taken to be <5 μm) and large (≥5 μm) cut-points did not differ significantly. Drift of pH and adsorption on filter holders appeared to be of secondary importance, but it was found that particle leakage can occur. Undissolved fractions and to some degree derived lung absorption parameters were observed to vary depending on the aerodynamic size fraction studied, suggesting that size fractionation (e.g., using cascade impactors) is appropriate prior to conducting in vitro dissolution rate experiments. The 0.01-0.02 μm and 1-2 μm size ranges are of particular interest as they correspond to alveolar deposition maxima in the Human Respiratory Tract Model (HRTM). In the present work, however, the dependency on aerodynamic size appeared to be of minor importance, but it cannot be ruled out that particle bounce obscured the results for late impaction stages. In addition, it was noted that the time over which simulated lung fluid samples are collected (100 d in our case) influences the curve-fitting procedure used to determine the lung absorption parameters, in particular the slow rate that increased if fewer samples were considered.

Effect of zeolite type, temperature, and pH on Stage III glass alteration behavior for two nuclear waste glasses

Long-term laboratory-scale static alteration tests (up to 1500 d) were conducted on two low-activity waste glasses (LAWA44 and IDF18-A161) at S/V = 2000 m–1. Tests were seeded with either analcime, clinoptilolite, zeolite P1, or zeolite P2 to induce Stage III glass alteration behavior. The effect of several parameters on glass Stage III behavior was studied with consideration of several variables, including temperature (22 °C–90 °C) and pH (floating or initially set using KOH at values from 9.5 to 11.5). Temporal solution data and solids characterization at the end of the experiments are reported. Solution data demonstrated the occurrence of a sustained rate acceleration at temperatures down to 40 °C and the activation energy for these Stage III rates was determined for both glasses. Three major secondary phases were identified at the end of the experiments for both glasses: zeolite P1, zeolite P2, and/or analcime (along with minor phases: zeolites, clays, carbonates). The identity of the crystalline phases at the end of the experiment often differed from the zeolite seed phase. In addition, the use of the Avrami equation showed unimpeded zeolite growth (3-dimensional) in certain conditions, suggesting that in certain conditions the glass dissolution rate is controlled by zeolite formation kinetics whereas in other conditions the glass corrosion process impeded zeolite formation kinetics. The morphological evolution of the samples revealed the growth of the zeolites which completely fill the intergranular space in the powder bed. These results are discussed with regards to previous seeded and unseeded Stage III dissolution rate experiments performed on low- and high-activity nuclear waste glasses.

Synthesis, Characterization, and Intrinsic Dissolution Studies of Drug-Drug Eutectic Solid Forms of Metformin Hydrochloride and Thiazide Diuretics.

The mechanochemical synthesis of drug–drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug–drug eutectic solids (DDESs). Further analysis by construction of binary diagrams (DSC screening) exhibited the characteristic V-shaped form indicating formation of DDESs in both cases. These new DDESs were further characterized by different techniques, including thermal analysis (DSC), solid state NMR spectroscopy (SSNMR), powder X-ray diffraction (PXRD) and scanning electron microscopy–energy dispersive X-ray spectroscopy analysis (SEM–EDS). In addition, intrinsic dissolution rate experiments and solubility assays were performed. In the case of MET·HCl-HTZ (χMET·HCl = 0.66), we observed a slight enhancement in the dissolution properties compared with pure HTZ (1.21-fold). The same analysis for the solid forms of MET·HCl-CTZ (χMET·HCl = 0.33 and 0.5) showed an enhancement in the dissolved amount of CTZ accompanied by a slight improvement in solubility. From these dissolution profiles and saturation solubility studies and by comparing the thermodynamic parameters (ΔHfus and ΔSfus) of the pure drugs with these new solid forms, it can be observed that there was a limited modification in these properties, not modifying the free energy of the solution (ΔG) and thus not allowing an improvement in the dissolution and solubility properties of these solid forms.

Development of a new chemical solvent package for increasing the asphaltene removal performance under static and dynamic conditions

In this work, a new solvent package (named TPMDS) for asphaltene removal under static and dynamic conditions was developed through a set of experiments. TPMDS consists of toluene, pyridine, methanol, surfactant dodecylbenzenesulfonic and sodium hydroxide. The optimum concentrations of TPMDS components were determined based on the efficiency evaluation of the chemical reagents to eliminate the asphaltene precipitation under static conditions. The highest effectiveness of the developed solvent package under static conditions was found to be 98%, which was observed at a soaking time of 6 h and a mass concentration of 1%. TPMDS had high performance (more than 97.5%) for asphaltene removal in four different oil samples containing various asphaltene concentrations. The results of the turbidity and dissolution rate experiments of asphaltene in the presence of TPMDS and toluene showed that the performance of TPMDS for asphaltene removal is significantly better than toluene. In addition, core flood tests were carried out with the use of TPMDS and toluene. Pressure drop due to asphaltene precipitation in the carbonate core samples was reduced eight times using the developed solvent package. The damaged permeability due to asphaltene deposition was 51% of the initial rock permeability before injection of any solvent. The results of core flood tests showed that the rock permeability has reached about 94% and 71% of the initial permeability after injection of TPMDS and toluene, respectively. Despite the increase in the amount of asphaltene precipitation in the core samples by increasing injection rate, the efficiency of the developed solvent was not decreased by changing the injection rate since the performance of the TPMDS was improved by the appearance of a synergistic effect for asphaltene dissolution. Furthermore, oil viscosity reduction with the use of TPMDS was more significant than with the use of toluene. The corrosion rate of the metal samples in the presence of the developed solvent package solution was less than 0.08 mm/year in a temperature range from 25 °C to 100 °C, which is less than an acceptable threshold corrosion rate of 0.1 mm/year. Moreover, the results of field analysis showed that the oil production rate could be enhanced by 3.3 times after treatment by TPMDS. Asphaltene removal effectiveness in the production wells using the industrial reagent and TPMDS has reached 84 and 96%, respectively. The rock permeability after treatment by TPMDS was increased by about 290%. TPMDS can be used for asphaltene removal in the near-wellbore region, production equipment, and tubing.

Pore-scale dissolution mechanisms in calcite-CO2-brine systems: The impact of non-linear reaction kinetics and coupled ion transport

We simulate two sets of dissolution experiments in which CO2-saturated solutions are injected into calcite formations. We explore the impact of non-linear reaction kinetics and charge-coupled ion transport in systems representing different levels of flow and mineralogical complexity. First, we flow CO2-saturated water and brine through cylindrical channels drilled through solid calcite cores and compare directly with experimental dissolution rates. We find that simulations using a linear saturation model match experimental results much better than the batch-reactor-derived non-linear saturation model. The use of a coupled diffusion model causes only a very small increase in the overall dissolution rate compared to a single diffusion coefficient, due to the increase in transport rates of reaction products, particularly the highly charged Ca2+ ion. We also determine the relative importance of the two calcite dissolution pathways, with H+ and H2CO3, and conclude that the H2CO3 – calcite reaction is by far the more dominant, in contrast with common assumptions in the literature. Then, we compare to the experiments of Menke et al. (2015) in which CO2-saturated brine was injected into a microporous Ketton carbonate, and compare dissolution rates over time. We find that including non-linear saturation behaviour markedly changes the simulated dissolution rate, by up to a factor of 0.7 in the case of the experimentally derived saturation model of Anabaraonye (2017), however neither case matches the experimental result which is several times slower than the simulation. Including the effects of coupled ion transport lead to virtually no change in overall dissolution rate due to the convection dominated behaviour. The model also shows differences in the trend of the dissolution rate over time observed in Menke et al, with an approximately linear relationship with time compared to the experimental square-root dependence on time. We conclude that the geochemical model may need to include other effects such as dissolution inside microporous regions.

Analysis on Temperature Dependent Corrosion of Tantalum in Acidic Fluoride Media

Tantalum (Ta) exhibits excellent corrosion resistance in most aqueous media as it forms chemically inert thin oxide layer when exposed to air or water. Due to the high corrosion resistance, Ta is used in chemical industries as lining material for piping, tanks and vessels (1). Although Ta possess excellent corrosion resistance, it dissolve very slowly in acidic fluoride media. In the present work, the corrosion rate of Ta in acidic fluoride media at different temperatures were measured from weight loss experiment and compare with the results of electrochemical Tafel extrapolation.The weight loss experiments were performed with Ta sheets of 2.5 × 2.5 cm with 1 mm thickness. Prior to the experiments, Ta sheets were polished with 0.3 µm alumina powder and cleaned by ultrasonicated in ethanol, rinsed in deionized water and dried with nitrogen gas. The temperature of the HF solution was maintained using a water bath and double-walled polypropylene beaker set up. The weight loss experiments were performed in various concentration of HF from 250 to 1000 mM HF and the experiments were also conducted by adding 250 mM KF/ H2SO4 into 500 mM HF solution to study the key HF dissociated species responsible for the corrosion of metal. The weight loss was measured at different temperature of the solution varied from 30 to 60 °C for any concentration of HF solution. In most of the experiments, the weight difference before and after the experiments were used to calculate the dissolution rate. A few experiments were also conducted wherein the weight was continuously monitored, so that the dissolution rate can be monitored as a function of time.The experimental dissolution rates of Ta in various concentrations of HF at different temperatures are shown in Fig. 1. An analysis of the results shows that corrosion of Ta is assisted by both undissociated HF and species. The activation energy of the reactions were estimated using Arrhenius expression, and the results show that Ta corrosion in acidic fluoride media is very sensitive to temperature and will proceed at rapid rates at high temperatures.The corrosion of Ta in acidic fluoride media at room temperature was also characterized using several electrochemical techniques, viz. Tafel extrapolation, electrochemical impedance spectroscopy and linear polarization. A comparison of the results of weight loss experiments show that Tafel extrapolation over predicts the corrosion rate, in most of the conditions. The EIS spectra obtained at OCP shows multiple loos (capacitive and inductive) in most of the concentrations and equivalent circuit analysis was used to estimate the R P value. The XPS analysis was also performed to understand the different metal oxide species present during the corrosion process. The results indicates that the dissolution process of Ta occurs viz. multiple intermediate steps.

Determination of actual dissolution rates from some rock properties in construction of deep salt cavern for natural gas storage

Available energy resources should be efficiently used to meet the global energy demand. The storage of energy resources, especially as natural gas, is important to balance extreme fluctuations in demand and supply of energy. Underground caverns in deep salt domes are used as storage for natural gas due to the low permeability and appropriate creep conditions of salt. Several projects are being carried out in Turkey to store imported natural gas. The design and construction parameters of these deep salt caverns should be determined to provide reliable and durable storage. Dissolution rate, which is an important parameter affecting the design and construction of underground salt caverns, is generally measured from core samples in laboratory settings. However, results do not match actual underground dissolution rates. The aim of this study was to predict actual dissolution rates from some rock properties. The physical and mechanical salt properties were determined from core samples obtained from different depths of drilled wells opened for salt caverns. The relationships between salt properties and actual dissolution rates were statistically analyzed. A statistical model was developed to predict actual dissolution rates using uniaxial compressive and tensile strengths, Poisson's ratio, and cohesion and experimental vertical dissolution rates. The model is reliable for predicting actual dissolution rates in construction of underground gas storage caverns in salt domes. Predicted dissolution rates can be used in the design of underground gas storage caverns in salt domes.

Onboard experiment investigating metal leaching of fresh hydrothermal sulfide cores into seawater

We observed the initial release rate of metals from four fresh (i.e., without long time exposure to the atmosphere) hydrothermal sulfide cores into artificial seawater. The sulfide samples were collected by seafloor drilling from the Okinawa Trough by D/V Chikyu, powdered under inert gas, and immediately subjected to onboard metal-leaching experiments at different temperatures (5 °C and 20 °C), and under different redox conditions (oxic and anoxic), for 1–30 h. Zinc and Pb were preferentially released from sulfide samples containing various metals (i.e., Mn, Fe, Cu, Zn, Cd, and Pb) into seawater. Under oxic experimental conditions, Zn and Pb dissolution rates from two sulfide samples composed mainly of iron disulfide minerals (pyrite and marcasite) were higher than those from two other sulfide samples with abundant sphalerite, galena, and/or silicate minerals. Scanning electron microscopy confirmed that the high metal-releasing sample contained several galvanic couples of iron disulfide with other sulfide minerals, whereas the low metal-releasing sample contained fewer galvanic couples or were coated by a silicate mineral. The experiments overall confirmed that the galvanic effects with iron disulfide minerals greatly induce the initial release of Zn and Pb from hydrothermal sulfides into seawater, especially under warm oxic conditions.

Chemical mechanisms of dissolution of calcite by HCl in porous media: Simulations and experiment

Abstract We use a pore-scale dissolution model to simulate the dissolution of calcite by HCl in two different systems and compare with experiment. The model couples flow and transport with chemical reactions at the mineral surface and in the fluid bulk. Firstly, we inject HCl through a single channel drilled through a solid calcite core as a simple validation case, and as a model system with which to elucidate the chemical mechanisms of the dissolution process. The overall dissolution rate is compared to a corresponding experiment. Close agreement with experimental and simulated dissolution rates is found, which also serves to validate the model. We also define a new form of effective Damkohler number which can be obtained from simulated chemical distributions, and show how this gives a more precise measure of the balance of transport and reaction. Secondly, we inject HCl into a Ketton carbonate rock core at high flow rate, which leads to wormhole formation, and compare to experiment. The simulation matches the experimental mass dissolution rate extracted from the micro-CT images, and predicts the resulting morphological changes reasonably well. The permeability change though is greater in the experiment than in the simulation, and this is shown to be due to more elongated wormhole formation in experiment. Possible reasons for this are discussed, including uncertainties in diffusion coefficients, and calcite density variations and micro-porosity in the Ketton grains. The distribution of chemical species from the simulation then permits a detailed understanding of the rate-controlling mechanisms at work, including the relative importance of the H+–calcite and H2CO3–calcite dissolution pathways.

Synthesis of Metforminium Succinate by Melting. Crystal Structure, Thermal, Spectroscopic and Dissolution Properties

The reaction by melt mixing at 220 °C of the antihyperglycemic drug metformin hydrochloride 1 with dehydrated sodium succinate yields efficiently the organic salt [MET]2[SUC] 2 (H-MET+= metforminium and SUC2- = succinate). Solid state CPMAS NMR 13C spectroscopy experiments, powder X-ray diffraction and FT-IR results support the formation of the pharmaceutical salt 2 in good yields. Besides, the charged-assisted hydrogen bonding interactions of type N-H…-O(carboxylate) were thoroughly analyzed by single crystal X-Ray diffraction techniques. Thus, the pharmaceutical salt 2 possesses considerable thermal differences when compared to the pure starting reagents. In addition, intrinsic dissolution rate experiments in buffered aqueous solutions at pH= 6.8 showed a sustained-release behavior of the drug in 2 with a constant value of Kint = 0.885 mg/min * cm2.

Predicting Pulmonary Pharmacokinetics from In Vitro Properties of Dry Powder Inhalers.

The ability of two semi-mechanistic simulation approaches to predict the systemic pharmacokinetics (PK) of inhaled corticosteroids (ICSs) delivered via dry powder inhalers (DPIs) was assessed for mometasone furoate, budesonide and fluticasone propionate. Both approaches derived the total lung doses and the central to peripheral lung deposition ratios from clinically relevant cascade impactor studies, but differed in the way the pulmonary absorption rate was derived. In approach 1, the rate of in vivo drug dissolution/absorption was predicted for the included ICSs from in vitro aerodynamic particle size distribution and in vitro drug solubility estimates measured in an in vivo predictive dissolution medium. Approach 2 derived a first order absorption rate from the mean dissolution time (MDT), determined for the test formulations in an in vitro Transwell® based dissolution system. Approach 1 suggested PK profiles which agreed well with the published pharmacokinetic profiles. Similarly, within approach 2, input parameters for the pulmonary absorption rate constant derived from dissolution rate experiments were able to reasonably predict the pharmacokinetic profiles published in literature. Approach 1 utilizes more complex strategies for predicting the dissolution/absorption process without providing a significant advantage over approach 2 with regard to accuracy of in vivo predictions.

Physicochemical Properties and In Vitro Dissolution of Spiramycin Microparticles Using the Homogenate-Antisolvent Precipitation Process

Due to its low bioavailability and slow dissolution rate, the micronized spiramycin powder was thus prepared by the homogenate-antisolvent precipitation (HAP) process. The optimum micronization conditions of the HAP process were found to be as follows: precipitation temperature of 4.6 °C, precipitation time of 10 min, spiramycin concentration of 20 mg/mL, dripping speed of the added solvent into the antisolvent of 44 mL/h, antisolvent (water) to solvent (dimethyl sulfide (DMSO)) volume ratio of 7:1, and shear rate of 5000 rpm. With this HAP process, the mean particle size was 228.36 ± 3.99 nm. The micronized spiramycin was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, high-performance liquid chromatography, and gas chromatograph analyses. In comparison with the raw drug, the chemical structure of micronized spiramycin was not changed. The dissolution rate experiments showed that the dissolution rate of the spiramycin was significantly increased after micronization.

Influence of spray drying and dispersing agent on surface and dissolution properties of griseofulvin micro and nanocrystals

The purpose for the current research is to compare and evaluate physiochemical properties of spray-dried (SD) microcrystals (MCs), nanocrystals (NCs), and nanocrystals with a dispersion agent (NCm) from a poorly soluble compound. The characterization was carried out by performing size and surface analysis, interfacial tension (at particle moisture interface), and in-vitro drug dissolution rate experiments. Nanosuspensions were prepared by media milling and were spray-dried. The SD powders that were obtained were characterized morphologically using scanning electron microscopy (SEM), polarized light microscopy (PLM), and Flowchem. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier transfer infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) for the identification of the crystalline nature of all the SD powders. The powders were characterized for their redispersion tendency in the water and in pH 1.2. Significant differences in redispersion were noted for both the NCs in both dissolution media. The interfacial tension for particle moisture interface was determined by applying the BET (Braunauer–Emmett–Teller) equation to the vapor sorption data. No significant reduction in the interfacial tension was observed between MCs and NCs; however, a significant reduction in the interfacial tension was observed for NCm at both 25 °C and 35 °C temperatures. The difference in interfacial tension and redispersion behavior can be attributed to a difference in the wetting tendency for all the SD powders. The dissolution studies were carried out under sink and under non-sink conditions. The non-sink dissolution approach was found suitable for quantification of the dissolution rate enhancement, and also for providing the rank order to the SD formulations.

Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine—A Study with Felodipine as a Model Drug

The aim of this study was to understand and predict the influence of hydrodynamic effects in the small intestine on dissolution of primary and aggregated drug particles. Dissolution tests of suspensions with a low-solubility drug, felodipine, were performed in a Couette cell under hydrodynamic test conditions corresponding to the fed small intestine. Dissolution was also performed in the USP II apparatus at two paddle speeds of 25 and 200 rpm and at different surfactant concentrations below critical micelle concentration. The experimental dissolution rates were compared with theoretical calculations. The different levels of shear stress in the in vitro tests did not influence the dissolution of primary or aggregated particles and experimental dissolution rates corresponded very well to calculations. The dissolution rate for the aggregated drug particles increased after addition of surfactant because of deaggregation, but there were still no effect of hydrodynamics. In conclusion, hydrodynamics do not influence dissolution and deaggregation of micronized drug particles in the small intestine of this model drug. Surface tension has a strong effect on the deaggregation and subsequent dissolution. Addition of surfactants at in vivo relevant surface tension levels is thus critical for in vivo predictive in vitro dissolution testing.

The Effect of Mg on Slag Reactivity in Blended Cements

Blast-furnace slags are widely used as supplementary cementitious materials in blended cements because of their relatively high reactivity. This study describes the effect of substituting Ca by Mg on the reactivity of synthetic glass with similar composition to slags, keeping the basicity ratio constant. The glass reactivity was assessed using a multi-technique approach including dissolution rate experiments at high dilution, calorimetry, X-ray diffraction combined with Rietveld quantitative phase analysis and electron microscopy image analysis of blended cement pastes. The effect of glass hydration on the hydration product assemblage was assessed by comparing experimental data to thermodynamic modelling. The results show that reactivity was not affected significantly by Ca by Mg substitution at constant basicity. The relative reactivities from the dissolution experiments, calorimetry and image analysis are in agreement and show a dependence of reactivity on basicity but not on Mg content. The release of Mg from the glasses led to the through-solution precipitation of hydrotalcite-like hydration products. Under the high pH conditions studied, there was no indication of incongruent glass dissolution or the formation of a leached passivating layer. The experimental results on changes in the cement hydration product assemblage by glass addition were supported by thermodynamic modelling and generally show an increase in calcium–aluminosilicate–hydrate, AFm, and hydrotalcite-type reaction products.

Will dawsonite form during CO2 storage?

AbstractFor more than a decade, a debate has been going on as to whether dawsonite can sequester CO2, and be the dominant secondary carbonate where reservoirs lack divalent metal cations. Numerical simulations have suggested large‐scale formation, whereas natural occurrences in present‐day or previously CO2‐charged reservoirs are scarce. Natural occurrences, such as in sequences of the Hailaer and Songliao basins, may nevertheless suggest that dawsonite can form under CO2 storage conditions (&lt;120 °C) given the right temperature‐composition window. The exact conditions, however (CO2 pressure, alkalinity, temperature, ionic strength) are highly uncertain. Moreover, there are no data on the rate of nucleation and growth of dawsonite, and numerical predictions are forced into using simplified kinetic expressions with values of kinetic constants obtained from far‐from‐equilibrium dissolution rate experiments, a method that is questioned today. There are good indications that a range of reservoirs may become supersaturated with respect to dawsonite during CO2 storage, but this does not imply spontaneous growth. The retention time (the nucleation stage) may be long, and growth rates may be significantly lower than predicted from the far‐from‐equilibrium dissolution rates. The lack of nucleation and growth rate data for dawsonite, the lack of dawsonite growth in laboratory experiments under CO2 storage conditions (not highly alkaline), and the uncertainty in growth conditions for the natural analogues, thus render numerical predictions highly uncertain. Conclusions on the mineral carbonatization potential should therefore be taken with caution if dawsonite is the dominant secondary carbonate predicted to form. © 2013 Society of Chemical Industry and John Wiley &amp; Sons, Ltd

Surfactant choice and the physical stability of nanosuspensions as a function of pH

Nanosuspensions of the example compounds ketoconazole and itraconazole were shown to aggregate upon reducing the pH to levels comparable to that known to exist in the stomach. Manipulation of the surfactant/polymer ratio in the suspension vehicle did not elucidate the cause of the aggregation. X-ray diffraction on ketoconazole solids failed to identify a form change as causative. Ultimately, ketoconazole intrinsic dissolution rate experiments implicated surface salt formation between ketoconazole and the vehicle surfactant as the cause of the aggregation. The generality of the phenomenon is discussed.

Dissolution of Weak Acids Under Laminar Flow and Rotating Disk Hydrodynamic Conditions: Application of a Comprehensive Convection–Diffusion–Migration–Reaction Transport Model

A steady-state mass transfer model that incorporates convection, diffusion, ionic migration, and ionization reaction processes was extended to describe the dissolution of weak acids under laminar flow and a rotating disk hydrodynamics. The model accurately predicted the experimental dissolution rates of benzoic acid, 2-naphthoic acid, and naproxen in unbuffered and monoprotic buffers within the physiological pH range for both hydrodynamic systems. Simulations at various flow rates indicated a cube root dependency of dissolution rate on the flow rate for a given bulk pH value for the laminar hydrodynamic system, as proposed earlier by Shah and Nelson (1975. J Pharm Sci 64(9):1518-1520) for neutral compounds. The model has limitations in its ability to accurately predict the dissolution of weak acids under certain conditions that imposed steep concentration gradients, such as high pH values, and for polyprotic buffer systems that caused the numerical solution to be unstable, suggesting that alternative numerical techniques may be required to obtain a stable numerical solution at all conditions. The model presents many advantages, most notably the ability to successfully predict the complex process under physiological conditions without simplifying assumptions, and therefore accurately representing the system in a comprehensive manner.

The dissolution rates of dawsonite at pH 0.9 to 5 and temperatures of 22, 60 and 77°C

► Obtained the dissolution rates of dawsonite at acidic conditions (pH 0.9–5). ► Obtained apparent activation energies for the dissolution. ► Compared to earlier published data on dawsonite dissolution (circumneutral pH, Hellevang et al., 2005 ). ► Because numerical simulations on CO 2 storage have used proxy minerals for dawsonite as data on the dissolution rates have not existed, the implications of the fast dissolution on the potential for long-term mineral storage is given. Occurrences of the mineral dawsonite (NaAl(OH) 2 CO 3 ) after natural CO 2 accumulation support suggestions that this mineral may contribute to long-term storage of CO 2 in geological formations. Knowledge of the reactivity of dawsonite is crucial to better understand its role as a CO 2 storage host. Here the results of free-drift batch dissolution rate experiments at 22, 60 and 77 °C performed on synthesized dawsonite are presented. Based on previously reported dawsonite dissolution rate data at circumneutral conditions and the present experiments, it is suggested that the dissolution rates can be expressed by two parallel mechanisms according to r + = k 1 a H + v + k 2 , where a H + denotes the proton activity. The rate coefficient k 1 (22 °C) and order with respect to the proton activity v were estimated from the 22 °C dataset to be 10 −4.48 ± 0.48 and 0.982 ± 0.15, respectively, at the 95% confidence level. The rate coefficient for the pH-independent region k 2 (77 °C) was found to be approximately 10 −6.89 from the maximum R 2 = 0.95 for the rate equation using the 77 °C dataset. The k 2 value was however uncertain because of the few data points in the transition into the pH-independent region. The apparent activation energy E a for the proton-promoted mechanism was estimated to 49.43 kJ/mol, increasing to 63.82 kJ/mol for the data points approaching pH independence. From the trends of data points for the 22 and 77 °C data series, it is likely that the difference in rates between 22 and 77 °C increases further at higher pH.