Modeling transdermal permeation. Part I. Predicting skin permeability of both hydrophobic and hydrophilic solutes

In this study, we present a modeling study on the prediction of transdermal permeability of both hydrophobic and hydrophilic solutes, using our recently reported mechanistic model of mass transfer in complex media, where the heterogeneous structure of the stratum corneum is represented by “bricks‐and‐mortar” model. The partition and diffusion properties of solutes in lipid matrix and corneocytes are calculated separately, without fitting to the modeled skin permeability data. Skin permeability has been predicted for a comprehensive experimental data set of chemicals compiled earlier. When the transcellular pathway is included, the agreement between predicted skin permeability and experimental data is much improved. The improvement is mainly due to better predicted results for hydrophilic solutes. The contribution of each pathway to the overall skin permeability has also been analyzed. The results showed that the transcellular pathway is important not only for highly hydrophilic solutes, but also for moderately hydrophobic solutes. © 2009 American Institute of Chemical Engineers AIChE J, 2010     

Combined experimental and computer simulation study of the kinetics of solute release from a relaxing swellable polymer matrix. II. Release of an osmotically active solute

The performance of a model monolithic controlled release device, consisting of a swellable polymeric matrix subject to structural relaxation (cellulose acetate), loaded with a simple osmotically active solute (NaCl) and activated by the ingress of solvent (water), was studied experimentally and by computer simulation. The former study involved detailed monitoring of the kinetics of both solute release and solvent absorption (followed in due course by desorption of osmotically imbibed excess solvent). The computer simulation study was based on extensive previous modeling work. Values of the relevant input model parameters were derived from independent experimental measurements of the sorption and diffusion properties of solvent (cf. Part I) and solute (reported in the present article). The resulting simulation was highly successful, considering that it proved possible to simulate closely and consistently the kinetics of both solute release (over practically the whole experimental range) and concurrent solvent absorption (including correct prediction of the magnitude of the osmotically induced excess swelling of the polymeric matrix). Simulation of the final desorption of osmotically imbibed water was facilitated by the realization that this process actually reflects the kinetics of a long‐term deswelling relaxation of the polymer structure back to the state of normal hydration, the rate of which could be measured to a good approximation on the pure deswelling polymer. The results presented here are of obvious practical significance in relation to progress toward computer‐assisted design of monolithic controlled release devices exhibiting relatively complex kinetic behavior. They should also prove useful by calling attention to an important caveat when desorption into water is used as a method for the straightforward determination of solute diffusivity in hydrated polymers, in cases of osmotically active solutes diffusing in nonhydrophilic polymers. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2468–2479, 2004     

Ionic conductivity of solid polymer electrolytes for dye‐sensitized solar cells

We developed an ionic conductivity model of solid polymer electrolytes for dye‐sensitized solar cells (DSSCs) based on the Nernst–Einstein equation in which the diffusion coefficient is derived from the molecular thermodynamic model. We introduced concentration‐dependence of the diffusion coefficient into the model, and the diffusion coefficient was expressed by differentiating the chemical potential by concentration. The ionic conductivities of polymer electrolytes (PEO/LiI/I₂ system) were investigated at various temperatures and compositions. We prepared a set of PEO in which an EO : LiI mole ratio of 10 : 1 was kept constant for PEO·LiI·(I₂)_n compositions with n = 0.02, 0.05, 0.1, 0.15, 0.2, and 0.3 (mole ratio of LiI : I₂). The ionic conductivities of the electrolytes were measured using a stainless steel/polymer‐electrolyte/stainless steel sandwich‐type electrode structure using alternating current impedance analysis. The values calculated using the proposed model agree well with experimental data. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

A novel equation of state (EOS) for prediction of solute solubility in supercritical carbon dioxide: Experimental determination and correlation

Solubility data of organophosphorous metal extractants in supercritical fluids (SCF) are crucial for designing metal extraction processes. We have developed a new equation of state (EOS) based on virial equation including an untypical parameter as BP/RT, reduced temperature and pressure for prediction of solute solubility in supercritical carbon dioxide (SC CO₂). Solubility experimental data (solubility of tributylphosphate in SC CO₂) were correlated with the two cubic equations of state (EOS) models, namely the Peng–Robinson EOS (PR‐EOS) and the Soave–Redlich–Kwong EOS (SRK‐EOS), together with two adjustable parameter van der Waals mixing and combining rules and our proposed EOS. The AARD of our EOS is significantly lower than that obtained from the other EOS models. The proposed EOS presented more accurate correlation for solubility data in SC CO₂. It can be employed to speed up the process of SCF applications in industry.     

Activation of lipase by sol–gel coating with hydrophobic alkyl‐substituted silicates in supercritical carbon dioxide

BACKGROUND: Sol–gel entrapment of lipases is usually performed in an aqueous solution. A novel method of sol–gel coating of lipase in supercritical carbon dioxide (SC‐CO₂) is proposed. RESULTS: Crude lipase powder (Rhizopus oryzae) coated with hydrophobic silicates, derived from dimethyldimethoxysilane and tetramethoxysilane in SC‐CO₂ at 35 °C and 15 MPa, exhibited 5–7 times higher esterification activity than that prepared via an aqueous sol–gel route. Lipase immobilized in a methyl‐substituted silica monolith was also highly activated by sol–gel coating using the same silica precursors in SC‐CO₂. CONCLUSION: Sol– gel coating in SC‐CO₂, of lipases in powder and immobilized forms with hydrophobic alkyl‐substituted silicates provides an efficient tool for the enhancement of enzymatic activities in non‐aqueous media. Copyright © 2009 Society of Chemical Industry     

A multi‐scale theoretical model for gas–Liquid interface mass transfer based on the wide spectrum eddy contact concept

On the basis of the wide spectrum eddy contact concept and the isotropic turbulence theory, a multi‐scale theoretical model for the prediction of liquid‐side mass transfer coefficient in gas–liquid system was developed. The model was derived from an unsteady‐state convection and diffusion equation and considered the contributions of eddies with different sizes to the overall mass transfer coefficient. The proper contact time distribution at the surface is need to be determined to obtain satisfactory results with this model. Moreover, a simplified model was also proposed based on the assumption of steady‐state mass transfer mechanism for single eddy. The results predicted by this model showed a very good agreement with the available experimental data in a comparatively wide range of turbulence intensities. © 2010 American Institute of Chemical Engineers AIChE J, 2011     

Combined experimental and computer simulation study of the kinetics of solute release from a relaxing swellable polymer matrix. I. Characterization of non‐Fickian solvent uptake

This article is concerned with a combined experimental and computer modeling study aimed at the characterization of the non‐Fickian absorption of liquid water by cellulose acetate (CA) matrices (in the form of thin films) on the basis of a strictly limited number of parameters. The observed kinetics exhibited two distinct non‐Fickian features, resulting from short‐term and long‐term viscous structural relaxations of the swelling glassy polymeric matrix. These relaxation processes were modeled by the extension of a previous model of micromolecular diffusion in a polymer subject to a single relaxation process. The successful simulation of the experimental kinetic curves then enabled the determination and cross‐checking of the relevant model parameter values. This work had the dual purpose of providing (1) input related to solvent absorption for the quantitative computer simulation (in part II of this series) of a model monolithic, solvent‐activated, controlled‐release device, consisting of a swellable glassy polymeric matrix (CA) loaded with an osmotically active solute (NaCl), and (2) an example of a general strategy of extracting meaningful values of micromolecular diffusivity in glassy polymers from non‐Fickian absorption kinetic data. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 2458–2467, 2004     

Synthesis and characterization of novel poly(acrylamide‐co‐acrylic acid‐co‐2‐hydroxy ethyl actylate) hydrogels: Mathematical approach in investigation of swelling kinetics and diffusion models

In this study, a series of poly(acrylamide‐co‐acrylic acid‐co‐2‐hydroxy ethyl actylate) [AM‐co‐AA‐co‐HEA] hydrogels have been synthesized by varying the acrylic acid (AA)content over eightfold in feed in the range of 33.34–93.76% by keeping other monomer constant. These hydrogels were characterized by FTIR, SEM analysis, elemental analysis, residual acrylic acid analysis, network parameters, and dynamic swelling behavior. The swelling study showed that equilibrium swelling ratio was nonlinearly increased with increasing AA content. Interestingly, the equilibrium swelling ratio decreased from 53.42 to 48.52 for 75–80% AA content hydrogel. The swelling data were found to satisfactorily fit Fick's second law, demonstrating that diffusion rate of water uptake was primarily Fickian. From model fitting, it was observed that early model was applicable for first 30% water absorption, and late model was applicable for latter 70% water absorption for increasing AA content from 33.34–90.90%. For 93.76% AA, early‐time model was extended up to first 50% of water absorption and late model was contracted for latter 50% water absorption, indicating that excessive AA content affects the applicability range of early‐time and late‐time diffusion models for water absorption. Etters model was best applicable to all type of hydrogels and followed over all swelling range. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Acetylsalicylic acid loading and release studies of the PMMA‐g‐polymeric oils/oily acids micro and nanospheres

Poly(methyl methacrylate) (PMMA) and PMMA copolymers derived from plant oils (Polylinseed oil‐g‐PMMA, Polysoybean oil‐g‐PMMA, Polylinoleic acid‐g‐PMMA (PLina‐g‐PMMA) and Polyhydroxy alkanoate‐ sy‐g‐Polylinoleic acid‐g‐PMMA (PHA‐g‐PLina‐g‐PMMA)) as hydrophobic polymers, a series of hydrophobic microsphere or nanosphere dispersions, were prepared by the emulsion/solvent evaporation method. The diameters of the nanospheres and microspheres were measured by dynamic light scattering with a zetasizer, optically and by scanning electron microscopy. The magnetic quality of the microspheres was determined by the electron spin resonance technique. Acetylsalicylic acid (aspirin, ASA) was used as a model drug and loaded into the microspheres during the preparation process. The effect of the stirring rate over the size and size distribution of the micro/nanospheres was evaluated, and the effects of copolymer types derived from plant oil/oily acids and the copolymer/drug ratios were evaluated. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Optimized ionic liquids for toluene absorption

Conductor‐like‐screening model for real solvents (COSMO‐RS) method was used to analyze the solute‐solvent interactions and to screen Henry's law constant of toluene over 272 ionic liquids (ILs), to select high‐capacity absorbents. Thermogravimetric experiments were carried out to evaluate the toluene absorption by selected ILs at different temperatures and atmospheric pressure. Experimental equilibrium data were found in good agreement with COSMO‐RS predictions. Complete desorption of toluene by N₂ stripping was achieved, indicating an easy regeneration. The kinetic curves were described by a phenomenological diffusion model, obtaining effective diffusivities in reasonable concordance with those calculated by Wilke–Chang correlation. The separation process with selected ILs was modeled by Aspen Plus and a comparison with organic absorbents was carried out. Equilibrium‐ and rate‐based simulations were used to analyze the importance of thermodynamics and kinetics in toluene absorption by ILs. Current computational‐experimental research allowed selecting a set of suitable ILs for toluene absorption. © 2012 American Institute of Chemical Engineers AIChE J, 59: 1648–1656, 2013     

Modeling of extraction behavior of docosahexaenoic acid ethyl ester by utilizing slug flow prepared by microreactor

The liquid–liquid extraction dynamics of an ethyl ester of docosahexaenoic acid (DHA‐Et) with silver ion was investigated. The kinetic model was derived according to the following stepwise processes: Diffusion of DHA‐Et across the organic film, complex‐formation between DHA‐Et and silver ion at the interface, and diffusion of extracted complex across the aqueous film. The kinetic parameters for the complex‐formation reaction were determined from the investigation with the stirred transfer cell. With the proposed model and determined parameters, we predicted the uptakes of DHA‐Et for the extraction system utilizing a slug flow prepared by a microchip. The calculated uptakes showed good correlation to the experimental data. The theoretical investigation suggested that the fast equilibration realized for the slug flow extraction system was due to the large specific interfacial area of the slug caused by the presence of wall film and the thin liquid film caused by the internal circulation. © 2009 American Institute of Chemical Engineers AIChE J, 2010     

Melt index prediction by RBF neural network optimized with an adaptive new ant colony optimization algorithm

Melt index (MI) is a crucial indicator in determining the product specifications and grades of polypropylene (PP). The prediction of MI, which is important in quality control of the PP polymerization process, is studied in this work. Based on RBF (radial basis function) neural network, a soft‐sensor model (RBF model) of the PP process is developed to infer the MI of PP from a bunch of process variables. Considering that the PP process is too complicated for the RBF neural network with a general set of parameters, a new ant colony optimization (ACO) algorithm, N‐ACO, and its adaptive version, A‐N‐ACO, which aim at continuous optimizing problems are proposed to optimize the structure parameters of the RBF neural network, respectively, and the structure‐best models, N‐ACO‐RBF model and A‐N‐ACO‐RBF model for the MI prediction of propylene polymerization process, are presented then. Based on the data from a real PP production plant, a detailed comparison research among the models is carried out. The research results confirm the prediction accuracy of the models and also prove the effectiveness of proposed N‐ACO and A‐N‐ACO optimization approaches in solving continuous optimizing problem. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

A comparative study on the free volume theories for diffusivity through polymeric membrane in pervaporation process

In this work, free volume theories are coupled with a thermodynamic model and generalized Fick's law to develop a mass transfer model based on solution‐diffusion mechanism for pervaporation process with a hydrophobic polymeric membrane. The Wesselingh, Fujita and Vrentas‐Duda's theories are used to calculate concentration‐dependent diffusion coefficient of permeants inside polydimethylsiloxane membrane. The sorption and pervaporation experiments on aqueous ethanol solutions are performed to validate the sorption and pervaporation models. The results reveal that the proposed models are able to predict influences of feed concentration and temperature as well as permeate‐side pressure on partial fluxes through the membrane. The comparative investigation indicated that Wesselingh's free volume theory underestimated the diffusion coefficients inside the membrane and the accuracy of the model used this theory is very low for prediction of the permeation flux. Generally, Fujita and Vrentas‐Duda's theories are found to be much more accurate especially for dilute aqueous feed solutions. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40581.     

Ionic salt permeability through phase‐separated membranes composed of amphoteric polymers

Amphoteric copolymers composed of hydrophilic poly(dimethyl acrylamide) and hydrophobic poly(dimethyl siloxane) formed phase‐separated membranes. The hydrophilic and hydrophobic components formed continuous phase‐separated domains in the membranes. The hydrated poly(dimethyl acrylamide) domains formed membrane‐spanning pathways, which permitted an ionic salt to permeate the membranes. The permeability of the ionic salt through the amphoteric copolymer membranes was studied. On the basis of the results, the mechanism of salt transport could be explained by the free‐volume theory, which was used for the analysis of diffusive transport in the hydrated, homogeneous membranes. The diffusion coefficient of the ionic salt increased exponentially as the volume ratio of the hydrophilic polymer to water [(1 − H)/H, where H is the degree of hydration] decreased in the membrane. It was possible to postulate that the diffusion of the ionic salt through the membranes was dependent on the free‐volume fractions of water and hydrophilic poly(dimethyl acrylamide) domains in the membranes. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Solute diffusion through swollen polymer membranes

Experiments were designed to study the role of the solvent in the transport of a solute through a solvent-swollen polymer membrane. A single solute (an organic dye), a single polymer (cross-linked natural rubber), and 24 different organic solvents were used for this purpose. The solute diffusion coefficient D was calculated from the measured permeability P and distribution coefficient K, and was compared to the diffusion coefficient of the solute in the pure solvent. The main parameters of the solvent were shown to be its viscosity and the degree it swells the polymer. At high swelling, the results are in agreement with a model that pictures the resistance to solute diffusion as hydrodynamic interaction with the solvent while the polymer acts as an obstruction that increases the tortuosity of the diffusion path. At very low swelling, the diffusion coefficient approaches an asymptotic limit which is independent of solvent viscosity. However, even with as low as 10% solvent, some effects of viscosity are still seen. These results are discussed in terms of a quantitative theory for the obstruction effect proposed by Meares and compared to other literature data.     

Adsorptive removal of uranium from water by sulfonated phenol–formaldehyde resin

Adsorption characteristics of a sulfonated phenol‐formaldehyde resin (SPR) have been studied for U removal from aqueous solution by means of batch method. Adsorption experiments have been carried out as a function of contact time, solution/adsorbent ratio, particle size and pH. Adsorption isotherm has been evaluated by changing adsorbent dosage in the range of 0.04–80 g/L at an initial uranyl nitrate concentration of 0.05 mol/L. The enormous adsorption capacity of 0.29 mol/g estimated from the plateau region of the S shaped isotherm is well comparable the Langmuir capacity of 0.31 mol/g. Equilibrium data are also adequately well described by the Freundlich and the Dubinin‐Radushkevich (D‐R) isotherm equations. The parameters of the isotherms and pH dependency of distribution coefficients (K_D) indicate that polymeric uranyl chains form on bidentate surface complex as a result of solute–solute interactions on the adsorbent surface. Both desorption and elution studies show that uranyl chains are irreversibly bounded on the SPR. Kinetic curves having a fast initial part followed by a slower process well fit both McKay model based on two‐resistance diffusion and Nernst‐Plank model with single diffusion coefficient. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Application of Single Molecule Fluorescence Microscopy to Characterize the Penetration of a Large Amphiphilic Molecule in the Stratum Corneum of Human Skin

We report here on the application of laser-based single molecule total internal reflection fluorescence microscopy (TIRFM) to study the penetration of molecules through the skin. Penetration of topically applied drug molecules is often observed to be limited by the size of the respective drug. However, the molecular mechanisms which govern the penetration of molecules through the outermost layer of the skin are still largely unknown. As a model compound we have chosen a larger amphiphilic molecule (fluorescent dye ATTO-Oxa12) with a molecular weight >700 Da that was applied to excised human skin. ATTO-Oxa12 penetrated through the stratum corneum (SC) into the viable epidermis as revealed by TIRFM of cryosections. Single particle tracking of ATTO-Oxa12 within SC sheets obtained by tape stripping allowed us to gain information on the localization as well as the lateral diffusion dynamics of these molecules. ATTO-Oxa12 appeared to be highly confined in the SC lipid region between (intercellular space) or close to the envelope of the corneocytes. Three main distinct confinement sizes of 52 ± 6, 118 ± 4, and 205 ± 5 nm were determined. We conclude that for this amphiphilic model compound several pathways through the skin exist.     

CO2 removal by single and mixed amines in a hollow‐fiber membrane module—investigation of contactor performance

This work investigates CO₂ removal by single and blended amines in a hollow‐fiber membrane contactor (HFMC) under gas‐filled and partially liquid‐filled membrane pores conditions via a two‐scale, nonisothermal, steady‐state model accounting for CO₂ diffusion in gas‐filled pores, CO₂ and amines diffusion/reaction within liquid‐filled pores and CO₂ and amines diffusion/reaction in liquid boundary layer. Model predictions were compared with CO₂ absorption data under various experimental conditions. The model was used to analyze the effects of liquid and gas velocity, CO₂ partial pressure, single (primary, secondary, tertiary, and sterically hindered alkanolamines) and mixed amines solution type, membrane wetting, and cocurrent/countercurrent flow orientation on the HFMC performance. An insignificant difference between the absorption in cocurrent and countercurrent flow was observed in this study. The membrane wetting decreases significantly the performance of hollow‐fiber membrane module. The nonisothermal simulations reveal that the hollow‐fiber membrane module operation can be considered as nearly isothermal. © 2014 American Institute of Chemical Engineers AIChE J, 61: 955–971, 2015     

Going Forward Laterally: Transmembrane Passage of Hydrophobic Molecules through Protein Channel Walls

Regular phospholipid bilayers do not pose efficient barriers for the transport of hydrophobic molecules. The outer membrane (OM) surrounding Gram‐negative bacteria is a nontypical, asymmetric bilayer with an outer layer of lipopolysaccharide (LPS). The sugar molecules of the LPS layer prevent spontaneous diffusion of hydrophobic molecules across the OM. As regular OM channels such as porins do not allow passage of hydrophobic molecules, specialized OM transport proteins are required for their uptake. Such proteins, exemplified by channels of the FadL family, transport their substrates according to a lateral diffusion mechanism. Here, substrates diffuse from the lumen of the β‐barrel laterally into the OM, through a stable opening in the wall of the barrel. In this way, the lipopolysaccharide barrier is bypassed and, by depositing the substrates into the OM, a driving force for uptake is provided. Lateral diffusion through protein channel walls also occurs in α‐helical inner membrane proteins, and could represent a widespread mechanism for proteins that transport and interact with hydrophobic substrates.     

Behavior of an organic solvent drop during the supercritical extraction of emulsions

The behavior of a drop of dichloromethane in water in contact with CO₂ at high pressure has been investigated with the purpose of analyzing the phenomena that takes place during the supercritical fluid extraction of emulsions process. Experiments have been performed with and without a solute (β‐carotene) and a surfactant (n‐octenylsuccinic anhydride‐modified starch) dissolved in the drop, and the evolution of the drop volume as well as of the interfacial tension between the drop and the aqueous phase has been measured. Additionally, a mathematical model has been developed that allows describing the mass transfer. Results show that the drop undergoes swelling and shrinking processes due to diffusion of CO₂ into the drop and dichloromethane out of the drop. CO₂ concentration in the drop can be as high as 0.9 (molar fraction). Emulsion drops behave as miniature gas antisolvent precipitators and many particles are formed inside the drop. The interfacial tension between the drop and the aqueous phase increases during the process, therefore destabilizing the emulsion. © 2009 American Institute of Chemical Engineers AIChE J, 2010