Diffuse Layer Model Research Articles

Physiologically Based Absorption Modelling to Explore the Formulation and Gastric pH Changes on the Pharmacokinetics of Acalabrutinib.

Acalabrutinib, a selective Bruton's tyrosine kinase inhibitor, is a biopharmaceutics classification system class II drug. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to mechanistically describe absorption of immediate release capsule formulation of acalabrutinib in humans. Integration of in vitro biorelevant measurements, dissolution studies and in silico modelling provided clinically relevant inputs for the mechanistic absorption PBPK model. The batch specific dissolution data were integrated in two ways, by fitting a diffusion layer model scalar to the drug product dissolution with integration of drug substance laser diffraction particle size data, or by fitting a product particle size distribution to the dissolution data. The latter method proved more robust and biopredictive. In both cases, the drug surface solubility was well predicted by the Simcyp simulator. The model using the product particle size distribution (P-PSD) for each clinical batch adequately captured the PK profiles of acalabrutinib and its active metabolite. Average fold errors were 0.89 for both Cmax and AUC, suggesting good agreement between predicted and observed PK values. The model also accurately predicted pH-dependent drug-drug interactions between omeprazole and acalabrutinib, which was similar across all clinical formulations. The model predicted acalabrutinib geometric mean AUC ratios (with omeprazole vs acalabrutinib alone) were 0.51 and 0.68 for 2 batches of formulations, which are close to observed values of 0.43 and 0.51~0.63, respectively. The mechanistic absorption PBPK model could be potentially used for future applications such as optimizing formulations or predicting the PK for different batches of the drug product.

Thermodynamic and kinetic coupling modeling for thallium(I) sorption at a heterogeneous titanium dioxide interface

The transformations of monovalent thallium (Tl) in an aqueous environment may be affected significantly by Tl(I) partitioning at the solid-water interface during sorption. Models used to quantify the kinetics of Tl(I) adsorption on heterogeneous adsorbents and formation of multiple complexes under a wide range of water chemistry conditions can accurately predict the environmental fate of thallium. In this study, Tl(I) sorption on representative titanium dioxide at different solution pH values and loading concentrations was investigated with two unified adsorption models, diffuse layer modeling and kinetics modeling. Three Tl(I) surface complexes, TiOTl, TiOHTl+, and TiOTlOH-, were used in the diffuse layer model and successfully described batch adsorption and the results of spectroscopic analyses. The contribution of TiOHTl+ to the adsorption capacity was much higher than those of TiOTl and TiOTlOH- under neutral and weakly alkaline conditions, while the species TiOTlOH- predominated among Tl(I) complexes in strongly alkaline environments. The adsorption and desorption rate coefficients derived from thermodynamics and kinetics coupling modeling suggested the influence of different complex characteristics on adsorption and desorption of Tl(I). Our results provide a comprehensive model for predicting the dynamic binding behavior of Tl at heterogeneous solid-water interfaces.

A calibrated surface complexation model for carbonate-oil-brine interactions coupled with reservoir simulation - Application to controlled salinity water flooding

Vast majority of past studies that have been conducted on controlled salinity water flooding (CSWF) use diffuse layer model (DLM) that calculates only the surface potential, which can be significantly different from the ζ-potential of the interface. Importantly, stability of the water-film (between the oil and the rock surface) which dictates ultimate oil recovery is related to ζ-potential. As such, using DLM calculated surface potential (directly) for CSWF can be misleading. Additionally, most of the existing DLMs use integer charges instead of fractional charges to model carbonate-brine interactions, which may not represent the actual carbonate crystallographic. We present a triple layer surface complexation model (TLM) which offers the option to locate and distribute charge of the adsorbing ion(s) at three locations. TLM can therefore calculate potentials at three different locations within the Stern layer. To the best of our knowledge, only few authors have used TLM to simulate CSWF. However, some surface reactions were ignored in these models. For instance, adsorption of monovalent ions such as Na + and Cl − ions was ignored in some of the few available TLMs. Also, the effect of basic-oil components was not considered in some TLMs, and lastly, some TLMs used integer charges for the carbonate surface group. This study introduced a comprehensive TLM that includes all these complexities. Moreover, we introduced a new wettability indicator (WI) that is related to the electrostatic forces between the oil-brine and the rock-brine interfaces. That is, WI was calculated from ζ-potentials at the oil-brine and rock-brine interfaces. The TLM, built in a geochemical simulator, PHREEQC, was then coupled with UTCHEM, a multiphase reservoir simulator. The developed simulator based on the TLM-CSWF model was tested against several experimentally measured oil recovery data sets. Results of the model suggest that Oil basic component significantly impacts oil-brine interface ζ-potential irrespective of temperature, brine composition, and ionic strength. On the otherhand, Na + ions in brine may influence oil-brine ζ-potential, and this relates to temperature, brine composition, and ionic strength. The results further suggest that injection of (sulfate-free) diluted brine in chalk resulted to increased oil adhesion, shifting the reservoir to oil-wet condition. Hence, no additional oil is recovered with this brine injected at tertiary oil recovery stage. Finally, the results showed that wettability is related to ζ-potentials at the oil-brine and rock-brine interfaces, and the carbonate rock would be strongly oil-wet or water-wet only at significantly large magnitude of ζ-potentials at the interfaces. • A new triple-layer surface complexation model developed to characterize carbonate-brine-oil interactions. • The model is tested against several experimentally measured zeta potential and oil recovery data sets. • The model suggests that SO 4 −2 ion adsorption tends to decrease CO 3 −2 adsorption at the rock surface and vice-versa. • The model showed that only a small fraction of the carbonate-oil-brine reactive sites are involved in the geochemical reactions.

Improvement of Diffusion Layer Model for Steam Condensation with the Presence of Noncondensable Gas Under Turbulent Free Convection

Improvement of Diffusion Layer Model for Steam Condensation with the Presence of Noncondensable Gas Under Turbulent Free Convection

Estimating electrodeposition properties and processes: Cu-Ag alloy at n-Si(001) and Ru substrates from acidic sulfate bath

In alloy electrodeposition, estimations of the initial transient and the potential vs. composition trend of the film system is important for material design, deposition procedure and the deposit characterization. However, solving the diffusion-migration-convection problem based on common simulation methods is often too burdensome and too resource-consuming for ordinary tasks in the context of alloy electrodeposition works. In this work, based on a stagnant diffusion layer model, we have proposed simple estimates on (1) the potential-composition curve, (2) the thickness of the initial deposit, and (3) the time interval to reach the steady state deposition. These estimates were validated by using a Cu-Ag acidic sulfate electrolyte, which upon electrodeposition results in an immiscible Cu-Ag alloy, both at n-Si(001) or at polycrystallline Ru substrates. The limiting current of Cu-Ag electrodeposition is compared with the numerical results given by Selman and Newman in 1970s [17], whereas the film composition deposited at the limiting current from various electrolyte constitutions is compared with the model suggest by Brenner based on stagnant diffusion layer model [21]. The proposed estimation methods show good agreement with the observed values, despite being highly simplified, since they are compared with the actual mass-transfer problem of ions under convection and migration.

Numerical Study of Convective Condensation Heat Transfers for Moist Air on a 3-D Finned Tube

The condensation of moist air is a common process in industry and increase its heat transfer coefficient is of great importance for improving energy efficiency. This study used 3-D finned tube to enhance moist air condensation, and the condensation process was calculated through numerical method aligned with Diffusion Layer model and Eulerian Wall Film model. The total heat transfer, sensible heat transfer and latent heat transfer during the condensation process were discussed. The results indicated that 3-D finned tube increased heat transfer amount and the condensation was mainly on fin surface. Besides, the influence of 3-D fin height was also obtained. The results indicated that the increase of fin height in circumferential direction can increase heat transfer in the tail of tube, and sensible heat transfer process was more sensitive to the area increment.

An experimental investigation on the swelling behavior of compacted B75 bentonite

Compacted bentonite is often utilized as a buffer material between the canister containing radioactive waste and the host rock in deep geological repositories. Extremely low permeability and a potential to swell and develop large swelling pressures upon hydration are desirable characteristics for such material. This study focused on the B75 bentonite, a Ca-Mg-montmorillonite-rich clay selected as a potential buffer material for the planned repository in the Czech Republic. The effects of the initial dry density, vertical load, and pore fluid salinity on the swelling behavior of the clay were investigated. One-dimensional swelling tests were performed on compacted samples prepared at various initial dry densities (1.25–1.95 g/cm3). Conventional oedometer tests with various hydration and stress paths were also performed. An empirically corrected diffuse double layer model proved successful in predicting the swelling pressure during the tests. Swelling under constant load, swelling pressure under constant volume, swelling upon unloading, and unconfined swelling upon hydration were compared, and a unique relationship was found between the effective stress and the dry density at saturation.

In Situ Observation at the Surface of Zinc in Alkaline Solution under Pulsed Current by Holographic Interferometry

Horizontal upward-facing zinc anode surfaces combined with Ni(OH)2/NiOOH cathodes in 1.95 M KOH aqueous solution were electrochemically dissolved and deposited with pulsed current. The morphological variations of zinc oxide were examined as a function of pulse width at three different locations on the anode surface using ex situ SEM observation. The particle size of zinc oxide varied with pulsed current for different pulse periods. Then, the transient variations in electrolyte for refractive index profiles along the axis perpendicular to the zinc anode were in situ measured under pulsed current using holographic interferometry. The oscillating layers of the refractive index profile were observed and related to a duplex diffusion layer model proposed by Ibl. Much more fine set up of SOC can be anticipated by combining the present results with HEV control (ECU) system.

Effects of the maximum Li stoichiometry in electrode on peak current densities of cyclic voltammogram

Cyclic voltammetry (CV) is widely used to study Li ion batteries. Most explanations of CV experiments, however, are based on traditional electrochemical kinetic models of all reactive species in electrolytes, possibly leading to non-physical lithium accumulation on electrode surfaces due to several orders of difference in magnitude between Li+ diffusion coefficients in electrode and electrolyte. Here, by considering size-effects of electrodes, we show that analytic expressions of the peak current density Ip of CV can be derived by combining Nernst diffusion layer model with conservation law of matter, leaving the coefficients of the analytic expressions undetermined. We then develop a complex model by considering the maximum stoichiometric intercalation sites (MSIS) of Li+ in electrode and name it as the MSIS model. Numerical simulations of the MSIS model on three shapes of electrodes confirm the validity of the analytic expressions, and the coefficients in the analytic expressions are determined from simulations. The plots of log(Ip) versus log(v) with v the scan rate show split lines, each of which can be further divided into low and high scan rate regions with two distinguished slopes, while the plots are always a single straight line in the MSIS-free model without the consideration of MSIS. The MSIS model and the present analytic and simulation results may provide a tool to characterize the MSIS effect and the Li+ diffusion coefficient in an electrode in experiments.

Effects of liquid film waviness, suction, and fog formation on condensation in the presence of noncondensable gases

The condensation of steam in the presence of noncondensable gas is critical in many industrial applications. However, a detailed understanding of the effects of liquid film waviness, suction, and fog formation in these diffusion models are still lacking. In this paper, a diffusion layer model was used to model the effects of liquid film waviness, suction and fog formation on steam condensation in the presence of noncondensable gases with the results verified by experimental data. The effect of the liquid film waviness becomes smaller as the noncondensable gas mole fraction increases, while the effect becomes larger as the total pressure and surface subcooling increase. The correction factor for the suction effect on the heat transfer and mass transfer decreases as the noncondensable gas mole fraction increases, but increases as the total pressure and surface subcooling increase. The correction factor for the fog formation effect on the heat transfer is positive while the correction factor for the fog formation effect on the mass transfer is negative. The fog formation effects on the heat and mass transfer both increase with increasing noncondensable gas mole fraction, surface subcooling and total pressure. The effects of liquid film waviness, suction, and fog formation on the heat and mass transfer for free convection condensation and forced convection condensation vary in the same way with increasing noncondensable gas mole fraction, surface subcooling and total pressure. The effects of noncondensable gas species are compared for He, Air and CO2 with condensing steam. The developed diffusion model can be used to estimate steam condensation heat transfer coefficient in the presence of noncondensable gas with an improved accuracy.

Application of spectroscopic evidence to diffuse layer model (DLM) parameter estimation for cation adsorption onto ferrihydrite in single- and bi-solute systems

The diffuse layer model (DLM) is one of the most frequently used surface complexation models (SCM) for predicting cation adsorption onto ferrihydrite. However, the DLM with its existing database sometimes fails to predict cation adsorption, especially in multi-solute systems. Notably, the failure is often attributed to inaccurate selection of the surface complexes and/or underestimation of the site density for DLM formulation. DLM simulations of batch adsorption data conducted with cadmium, copper, lead, and zinc on ferrihydrite in CO2 free systems demonstrates the ability of the DLM to fit single-solute data reasonably well but highlights its limitations with respect to predicting bi-solute data. Modifications to the DLM were made in two steps. First, spectroscopic evidence was used to guide cation complexation reactions at the ferrihydrite surface. Second, surface characteristics (reactive site density, specific surface area, and acidity constants) of ferrihydrite were updated according to recent literature. Results from this study suggest that when spectroscopic verification is employed and surface site density is increased, a simple two-site DLM can predict cation adsorption on ferrihydrite in single-solute systems for pH data above 3.5 and in most of the bi-solute systems tested.

Application of surface complexation modeling on adsorption of uranium at water-solid interface: A review.

Precise prediction of uranium adsorption at water-mineral interface is of great significance for the safe disposal of radionuclides in geologic environments. Surface complexation modeling (SCM) as a very useful tool has been extensively investigated for simulating adsorption behavior of metals/metalloids at water-mineral interface. Numerous studies concerning the fitting of uranium adsorption on various adsorbents using SCM are well documented, but the systematic and comprehensive review of uranium adsorption using various SCM is not available. In this review, we briefly summarized the rationale of SCM, including constant-capacitance-model (CCM), diffuse-layer-model (DLM), triple-layer-model (TLM); The recent progress in the application of SCM on the fitting of uranium adsorption towards metal (hydr)oxides, clay minerals and soil/sediments was reviewed in details. This review hopefully provides the beneficial guidelines for predicting the transport and fate of uranium in geologic environments beyond laboratory timescales.

Condensation heat transfer for downward flows of superheated steam-air mixture in a circular pipe

We measured the radial and axial temperature distributions of a saturated steam-air mixture in a vertical circular pipe (diameter, 49.5 mm; cooling height, 610 mm) in our previous study. Those of a superheated steam-air mixture in the same experimental setup were measured in this study. The condensation heat flux qc and heat transfer coefficient hc for the superheated mixture were evaluated, and they were compared with those for the saturated mixture. There was no large difference in qc between the saturated and superheated mixtures. The heat transfer coefficient hc (which was evaluated for the saturation temperature) for the superheated mixture agreed with that for the saturated mixture. hc computed with the diffusion layer model for saturated temperature agreed well with the hc measured for the superheated mixture.

(Invited) Short Introduction of Brenner’s Paradigm on the Steady State Diffusion Layer Model of Alloy Electrodeposition Composition Control, and Its Possible Extensions

Understanding the composition control of alloy electrodeposition is the prerequisite of pursuing fundamental understandings of phase and morphology evolution in the deposit. It is well known that a constant electrolyte concentration boundary, called diffusion layer, will form when the system is under forced convection or natural convection.[1] Given enough time, the thickness of diffusion layer, which in the beginning follows the Cottrell equation, will reach a steady state value, and thus a steady state deposition flux rate and deposition current could be estimated using the ionic diffusivity and diffusion layer length. For alloy electrodeposition, using the steady state deposition flux rate, ideally, the composition of the deposit could be predicted by the concentration ratio in the electrolyte and the mass-transfer coefficient ratio of the depositing ions.Despite being proposed by Essin in the 1930s and systematically documented in Brenner’s famous alloy electrodeposition book in the 1960s,[2, 3] nowadays, this behavior seems to be set aside when investigating the alloy electrodeposition properties. We decided to summarize the recent evidence for the composition control at the limiting case of diffusion layer control (limiting current condition) and discuss the confusions we are facing when applying this paradigm of alloy electrodeposition composition control at steady state.In this presentation, we will tentatively present the following topics: Levich in the 1960s has estimated the diffusion layer thickness of the electrodeposition on a vertical plate without any forced convection: when depositing in low viscosity electrolytes without forced convections, the natural convection will be induced by the tiny variation of local electrolyte density of the electrolyte and lead to the formation of diffusion layer.[4, 5] We will briefly present his model and derivation. From this model, the diffusion layer thickness due to 0.01mM Ni(II) at the height of 1 cm on the vertical electrodecould be as much as 0.21 cm. The time for reaching the steady state diffusion layer thickness and the initial layer thickness of the deposit (assuming two elements start to be deposited simultaneously) is estimated using the Cottrell equation.Expansion of mass-transfer coefficient to higher orders with respect to concentration, under the circumstances of multi-component, multi-element alloy electrodeposition. The matrix for multicomponent system could be fitted from the experimental data with a designated order of approximation on the mass-transfer coefficient. We will give the example for fitting the simplest case: binary system with linear behavior, based on data mentioned in our AgFe DMH-citrate work, where both ions are complexed as anions and deposited under limiting current condition. Meanwhile, a tentative construction of multi-element electrodeposition is given from the tabulated ionic diffusivities and a fixed diffusion layer thickness.Non-linear behaviors of deposit composition ratio - electrolyte concentration ratio sometimes happen in the alloy electrodeposition comparing with the prediction from the diffusion layer model. We will conceptually discuss the several possible causes for this non-linear behavior: the existence of homogeneous reaction inside the diffusion layer due to the pH and ligand concentration variation,[6] the transition from laminar flow to turbulent flow of the electrolyte near the electrode due to hydrogen bubbles and high deposition rate,[1] the formation of extended charge region at the cathode under overlimiting current,[7] and the situations where charge transfer kinetics governs the overall deposition rate.

A model for discrete fracture-clay rock interaction incorporating electrostatic effects on transport

A model based on the code CrunchClay is presented for a fracture-clay matrix system that takes electrostatic effects on transport into account. The electrostatic effects on transport include those associated with the development of a diffusion potential as captured by the Nernst-Planck equation, and the formation of a diffuse layer bordering negatively charged clay particles within which partial anion exclusion occurs. The model is based on a dual continuum formulation that accounts for diffuse layer and bulk water pore space, providing a more flexible framework than is found in the classical mean electrostatic potential models. The diffuse layer model is obtained by volume averaging ion concentrations in the Poisson-Boltzmann equation, but also includes the treatment of longitudinal transport within this continuum. The calculation of transport within the bulk and diffuse layer porosity is based on a new formulation for the Nernst-Planck equation that considers averaging of diffusion coefficients and accumulation factors at grid cell interfaces. Equations for function residuals and the associated Jacobian matrix are presented such that the system of nonlinear differential-algebraic equations can be solved with Newton’s method. As an example, we consider a 2D system with a single discrete fracture within which flow and advective transport occurs that is coupled to diffusion in the clay-rich matrix. The simulation results demonstrate the lack of retardation for anions (e.g., 36Cl−) of the contaminant plume within the fracture flow system because they are largely excluded from the charged clay rock, while the migration of cations (e.g., 90Sr++) is more strongly attenuated. The diffusive loss of divalent cations in particular from the fracture is accentuated by their accumulation in the diffuse layer within the clay-rich matrix.

Simple method for evaluating swelling of GMZ01 Na-bentonite affected by temperature at osmotic swelling

Swelling deformation tests of GaoMiaoZi (GMZ01) bentonite were performed at 25, 40 60, and 90 °C in distilled water. Experimental results suggested that the maximum swelling strain of GMZ01 bentonite increased with temperature, due to the osmotic swelling dominated the swelling. The em − σv relation for compacted bentonite at a same temperature can be expressed as em=KσvD-3 (em is montmorillonite void ratio, σv is vertical stress). The fractal dimension, D, of GMZ01 bentonite was unaffected by the temperature according to the results of N2 adsorption tests. Calculated by the diffuse double layer (DDL) model under the condition of osmotic swelling, a linearly relation was found between the montmorillonite swelling coefficient K and temperature Tc. Combing the fractal em − σv relation and linear K − Tc relation, a simple method for evaluating the swelling of GMZ01 bentonite affected by temperature was proposed.

A diffuse layer model for hydrocarbon mass transfer between pores and organic matter for supercritical CO2 injection and sequestration in shale

CO2 injection in shale oil reservoirs is a feasible method for CO2 geological sequestration and enhanced oil recovery. However, the mechanisms of mass transfer in inorganic pores and organic matter (kerogen) are still ambiguous. In this study, the mechanisms of diffusion and extraction were investigated. A novel pore-kerogen diffuse layer (PKDL) model was proposed for mass transfer between kerogen matrix and pores (inorganic pores and organic pores). Mathematical models for hydrocarbon mass transfer in spherical and cylindrical shaped rocks were derived. The predicted responses of the mathematical models closely matched the experimental data of CO2 injection experiments performed on various shales and tight rocks at high pressure and high temperature conditions. Hydrocarbon recovery of shales shows a delayed effect compared to tight rocks due to the additional extraction process between supercritical CO2 and kerogen. Hydrocarbons were extracted out of the kerogen matrix and then diffused through the inorganic and organic pores. Hydrocarbon diffusion coefficients ranged from 0.61 to 3.3 × 10−7 m2/s and extraction rate coefficients varied from 1.7 to 4.9 × 10−5 s−1 for shale rocks. Hydrocarbon diffusion coefficients varied from 0.49 to 4.8 × 10−7 m2/s for tight rocks. Both diffusion coefficients and extraction rate coefficients decreased exponentially with carbon numbers. The extraction rate coefficients decreased exponentially because the diffusion coefficients of hydrocarbons in kerogen also decreased exponentially with carbon numbers. This research advances the diffusion and extraction theories in shale rocks and promotes the injection and sequestration of CO2 in shale formations.

Probing and understanding interaction of Eu(III) with γ- alumina in presenceof malonic acid

Radionuclide migration in aquatic environment is influenced by its sorption onto colloids/mineral oxides and the presence of organic complexing anions. With a view to understand the sorption of trivalent actinides by mineral oxides in presence of organic acid, in the present study, Eu(III), malonic acid (MA) and γ-alumina are considered as representatives of trivalent actinides, low molecular weight natural occurring organic acid and aluminol sites, respectively. The influence of MA on sorption of Eu(III) by γ-alumina was elucidated by batch sorption, spectroscopic techniques and surface complexation modeling, for the first time. Attenuated Total Reflection-Fourier Transform Infrared spectroscopic studies of MA sorbed on γ-alumina revealed the presence of two inner-sphere surface complexes. Batch sorption for binary (alumina-Eu(III)) and ternary (alumina-Eu(III)-MA) systems were investigated as a function of pH, Eu(III) concentration and sequential addition of Eu(III)/MA. The pH edge for Eu(III) sorption shifts to higher pH with increasing Eu(III) concentration. In ternary systems, Eu(III) sorption is significantly enhanced at pH < 4.5. Eu(III) speciation on γ-alumina is independent of addition sequence of Eu(III)/MA. Time resolved fluorescence spectroscopy of Eu(III) sorbed on γ-alumina exhibited two surface species, XOEu2+ and (YO)2Eu+. The enhancement in I616/I592 and lifetime for ternary systems, as compared to binary system, at low pH, indicates the participation of Eu-MA complexes in the formation of surface species in ternary systems. The diffuse layer model has been employed to successfully model the experimental sorption profiles of binary and ternary systems, using code FITEQL 4.0, by considering the surface species identified by spectroscopic techniques.

A 2D numerical study on the condensation characteristics of three non-azeotropic binary hydrocarbon vapor mixtures on a vertical plate

To improve the transportation efficiency and reduce the supply cost, the liquefaction becomes an important technology to store and transport the natural gas. During the liquefaction, the various components (e.g. propane, ethane, methane etc.) undergo fractional condensation phenomenon due to their different boiling points. This means that when one component condenses, others play a role of non-condensable gas (NCG). In order to reveal the influence mechanism of NCG on this condensation process, a numerical method was employed in this paper to study the condensation characteristics of three non-azeotropic binary hydrocarbon vapor mixtures, namely the propane/methane (80%–95%), ethane/methane (65%–85%) and methane/nitrogen (2%–13%) mixtures, on a vertical plate. The model was proposed based on the diffusion layer model, and the finite volume method was used to solve the governing equations. A user defined function was developed by cell iterative method to obtain the source terms in the condensation process. The numerical results show that the gas phase boundary layer formed by the NCG becomes the main resistance to the reduction of heat transfer coefficient. And for the above three mixtures, there is a negative correlation between the NCG concentration and the heat transfer coefficient. Meanwhile, the results show a good agreement with the experimental data, meaning that the proposed model is reliable. Three mixtures within same non-condensable mole fraction of 20% were also investigated, indicating that the mixtures with a higher binary hydrocarbon molecular ratio have a lower heat transfer coefficient. As a result, the presence of the lighter NCG contributes to a thicker boundary layer.

Physiologically based pharmacokinetic model outputs depend on dissolution data and their input: Case examples glibenclamide and dipyridamole

A plethora of dissolution tests exists for oral dosage forms, with variations in selection of the dissolution medium, the hydrodynamics and the dissolution equipment. This work aimed at determining the influence of media composition, the type of dissolution test and the method for entering the data into a PBPK model on the ability to simulate the in vivo plasma profile of an immediate release formulation.Using two rDCS IIa substances, glibenclamide and dipyridamole, housed in immediate-release formulations as model dosage forms, dissolution tests were performed in USP apparatus II with the biorelevant media FaSSGF, FaSSIF V1, V2 and V3 using both single-stage and two-stage test designs. The results were then integrated into the PBPK software SimcypⓇ either as the observed release profile (dissolution rate model, DRM) or using a semi-mechanistic model (diffusion layer model, DLM) and compared with in vivo plasma profiles.The selection of the FaSSIF version did not appear to have any relevant influence on the dissolution of the weakly basic dipyridamole, while the weakly acidic glibenclamide was sensitive to the difference in pH between FaSSIF V1, V2 and FaSSIF V3. Since both compounds have pKa values close to the pH of biorelevant media representing conditions in the small intestine, these results may be specific to compounds with similar ionization behavior. Single-stage and two-stage testing led to equivalent simulations for glibenclamide. Only results from the single-stage test in FaSSGF led to a close simulation of the pharmacokinetic profile of dipyridamole when data were inputted using the DRM, while simulations from two-stage testing were most similar to the observed pharmacokinetic profile when DLM with selection of a dynamic pH profile in the small intestine was selected as the data input method. These results emphasize the importance of data input to the simulation results.