Application of the transverse differential swelling stress model to the interpretation of case II diffusion kinetics

Attention is called to an early observation of Case II diffusion kinetics during penetration of a liquid into a uniaxially prestretched polymer film along the axis of stretching. Application of a previously developed transverse differential swelling stress model to these experimental conditions is described. It is shown that the model can predict Case II diffusion kinetics in a physically meaningful manner and will also explain the transition of the kinetics of the above system into normal or hindered diffusion regimes as either the degree of stretching or its direction relative to that of penetration is changed.     

Phenomenology and mechanisms of unidimensional stress-dependent micromolecular transport in a stiff-chain polymer. III. Effect of modification of the polymer

A detailed study of the kinetics and mechanism of micromolecular transport in cellulose acetate films containing 2.0 acetate groups per glucose unit (CA-2.0) is reported. The polymer was prepared by controlled hydrolysis of CA-2.45 films studied in preceding articles. The same series of simple liquid penetrants varying from weak swelling agent to good solvent of the polymer was used. As before, measurement of rates of penetration along the polymer film confined between glass plates was supplemented with information on penetrant distribution profiles in the polymer film and on the corresponding deformation and structural relaxation of the swelling polymer, deduced from refractive index and birefringence profiles, respectively. Transport was studied in (a) unoriented CA-2.0 films and (b) uniaxially oriented films with penetration normal and parallel to the orientation axis. This was equivalent to varying the viscoelastic polymer properties affecting transport, under otherwise identical experimental conditions. The results complemented and extended those previously obtained with CA-2.45 in interesting ways and were successfully interpreted on the basis of a previously developed theoretical model designed to represent the influence of (a) the stress generated by the constraints imposed on the swelling polymer, and (b) the viscoelastic response of the latter thereto, on the transport mechanism. It was shown that the observed differences in transport mechanism in CA-2.45 and CA-2.0 are primarily related to the corresponding changes in the sorptive capacity of the polymer for the relevant penetrant rather than the chemical constitution of the latter. The most striking result in this respect was that the remarkable kinetic pattern (which involved a drastic change from Case I kinetics for penetration across, to Case II kinetics for penetration along, the axis of orientation) exhibited by oriented CA-2.45 film penetrated by the strong swelling agent of the series of penetrants used, namely methylene chloride, was reproduced here for the penetration of acetone, which occupies the slot of strong swelling agent in the case of CA-2.0. © 1997 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 35 : 2593–2607, 1997     

ARXPS investigation of diffusion as a limiting process in the incorporation of adatoms into polystyrene surfaces treated by nitrogen plasmas

Polystyrene films were exposed to nitrogen plasmas for periods up to 4 min. ARXPS measurements revealed the presence of oxygen and nitrogen in the surface because of the plasma treatment. The depth profiles of these adatoms were determined by fitting a Thomas–Windle model profile to the data. As found previously, the best‐fit depth profiles resembled a step function, consistent with case II diffusion. However, the depth of penetration of the adatom species into the polymer surface was not found to vary with plasma duration, which is inconsistent with Case II diffusion, and provides evidence that diffusion processes do not limit the loading of adatom species into the surface during nitrogen plasma treatment. A possible reason for the generation of erroneous step function depth profiles is discussed. Copyright © 2007 John Wiley & Sons, Ltd.     

双组分冷模射流流化床气化炉内流体动力学特性模拟

针对实际工业生产中经常遇到的多组分体系，本文选取了具有代表性意义的非等密度/直径的双组分体系(树脂和砂子)为研究对象，以Goossens等提出的平均物性法则计算了固体混合物的平均粒径和平均密度，采用欧拉－欧拉计算流体动力学模型(CFD)模拟了二维冷模射流床气化炉内，诸如气、固相流场的时空分布、时均空隙率分布、射流穿透深度等流体动力学的时空特征，所得结果与文献报道相吻合。     

Determination of coherence length of a smectic liquid crystal

A model for the near surface director profile in a homeotropically aligned smectic liquid crystal is developed based on the idea of the two independent anchoring energies separately associated with the director and the density wave at the surface. These anchoring energies are counterbalanced by the tendency to form the smectic C phase in the bulk. The model yields simple distance-dependent cone angle profiles which are compared with experimental data obtained from the half-leaky waveguide technique to obtain the coherence length for the penetration of the smectic C phase into the smectic A phase and the ratio of the surface to bulk cone angles.     

Applicability of shrinking core model on the adsorption of heavy metals by clarified sludge from aqueous solution

Shrinking Core model, widely accepted in the solid-fluid non-catalytic reaction system was applied to analyze the adsorption of metal ions like Zn(II), Cr(VI), Cd(II) and Pb(II) from the aqueous solutions onto the clarified sludge (CLS). The diffusivities of different metal ions in clarified sludge were determined by global optimization. The depth of penetration was also estimated for different initial concentrations. The experimental concentration profiles at various initial concentrations for all these four different metal ions matched well with the model predictions.     

Evaluation of the predicted time-concentration profile of serum tulobuterol in human after transdermal application

We proposed an in vitro/in vivo/in silico method for evaluating the clinical performance of matrix type transdermal therapeutic systems (TTSs). This method is based on the following four approaches: (1) drug release experiment, (2) in vitro penetration experiment using excised hairless mouse skin, (3) clinical pharmacokinetic study, and (4) mathematical model for evaluating the pharmacokinetic profile. The tulobuterol TTS was used as an example of a matrix type TTS in this study. The drug diffusion coefficient in the matrix device was calculated from the result of the release experiment. The drug diffusion coefficient and the partition coefficient in the skin were calculated from the results of in vitro skin penetration experiments where hairless mice and rats were used. Those parameters were used as substitutes of human. Further, these parameters were used for solving the governing partial differential equation on skin penetration. The time profiles of the serum concentration in human after applying the tulobuterol TTS were predicted and compared with the clinical data. The predicted profiles obtained from the data of hairless mice reproduced the influence of drug depletion adequately and well agreed with the clinical data, while those from the data of rats differed clearly in the initial rise. This method is useful for prediction of pharmacokinetic profiles of TTSs.     

INVESTIGATION OF POWER ABSORPTION BY METHYLENE BLUE IN A LIGHT SCATTERING MEDIUM WITH AN INTERNAL PHOTODYNAMIC ACTINOMETER

Abstract— Power absorption by aqueous solutions of methylene blue containing high concentrations of polystyrene microspheres was measured at 650 nm, using the photosensitized inactivation of subtilisin Carlsberg as an internal actinometer. The results were analyzed with the one-dimensional diffusion approximation for a finite slab. It is shown that the power absorption is determined by two macroscopic parameters, the optical penetration depth and the linear absorption coefficient. The optical penetration depth was determined independently by measuring flux profiles with an inserted fiber-optic method. The results are in satisfactory agreement with the predictions of the diffusion model, with microsphere diameters from 0.5 to 5 μm and a wide range of scatterer and dye concentrations. The presence of the scatterers diminished the power absorbed by the dye in all cases. The predictions of one-dimensional diffusion model are compared to Kubelka-Munk theory, and shown to be equivalent for optically dense systems     

Drug penetration of the posterior eye tissues after topical instillation: in vivo and in silico simulation

The purpose of this study was to analyze drug pharmacokinetics in the posterior eye tissues after topical instillation. For the in vivo study, the concentrations of ofloxacin in rabbit ocular tissues were analyzed by high performance liquid chromatography at 1, 2, and 3 h after instillation. For the in silico simulation, the concentration distribution of ofloxacin in the eye was calculated by the ocular pharmacokinetic model based on the diffusion/partition model. The simulated profiles were then compared with the in vivo experimental findings. In the in vivo study, the drug concentration in the posterior vitreous body initially decreased with time after topical instillation, and thereafter, the concentration increased. The in silico simulation of ocular pharmacokinetics indicated that the drug penetration of the posterior vitreous body was determined by three major pathways: (1) the initial transscleral penetration, (2) the intermediate transcorneal penetration, and (3) the late transretinal penetration. The in vivo findings were well described by a series of contributions by these three pathways. In conclusion, the present in vivo and in silico studies suggest that the instilled drugs initially reached the posterior vitreous body by diffusion through the sclera and then later by corneal penetration and systemic circulation.     

Implementation of depth-dependent soil concentrations in multimedia mass balance models

In standard multimedia mass balance models, the soil compartment is modeled as a box with uniform concentrations, which often does not correspond with actual field situations. Therefore, the theoretically expected decrease of soil concentrations with depth was implemented in the multimedia model SimpleBox 3.0. The effects of this implementation on the model outcomes were explored for nine compounds in four environmental compartments. For compounds with a low penetration depth, the new model predicts substantially higher or lower concentrations in the vegetation compartment than the old model. For those compounds, predicted concentrations in surface water and air were higher in the new model, but the deviations from the old model were smaller than in the vegetation compartment. For compounds with a large penetration depth, the model adaptations show little effect. No field study was carried out to validate the results of the model calculations, but we did collect measured data on concentrations in vertical soil profiles from literature. According to those data, we concluded that the implementation of depth dependent soil concentrations might be a useful extension for steady state multimedia mass balance models. More field study has to be carried out to validate the model outcomes.     

Implementation of depth-dependent soil concentrations in multimedia mass balance models

In standard multimedia mass balance models, the soil compartment is modeled as a box with uniform concentrations, which often does not correspond with actual field situations. Therefore, the theoretically expected decrease of soil concentrations with depth was implemented in the multimedia model SimpleBox 3.0. The effects of this implementation on the model outcomes were explored for nine compounds in four environmental compartments. For compounds with a low penetration depth, the new model predicts substantially higher or lower concentrations in the vegetation compartment than the old model. For those compounds, predicted concentrations in surface water and air were higher in the new model, but the deviations from the old model were smaller than in the vegetation compartment. For compounds with a large penetration depth, the model adaptations show little effect. No field study was carried out to validate the results of the model calculations, but we did collect measured data on concentrations in vertical soil profiles from literature. According to those data, we concluded that the implementation of depth dependent soil concentrations might be a useful extension for steady state multimedia mass balance models. More field study has to be carried out to validate the model outcomes.     

Diffusion-controlled penetration of polymethyl methacrylate sheets by monohydric normal alcohols

The kinetics of ethanol, n-propanol, and n-butanol penetration, sorption, and dimensional swelling in 2 mm poly(methyl methacrylate) sheets were determined over the temperature range 50–95°C. At 50°C, Case II relaxation-controlled transport dominated the observed sorption and penetration kinetics for all three alcohols. At higher temperatures, diffusion of swelling penetrant to the relaxing boundary contributes increasingly to the observed sorption kinetics. In addition, as the temperature is raised, the completion of sorption lags significantly behind the penetration of the relaxing boundary to the sheet midplane. p]The activation energy describing low temperature penetration is significantly higher than the activation energy describing the temperature dependence of high temperature penetration. A distinct transition in the penetration kinetics is apparent for all three alcohols at approximatively 65°C. Independent Clash—Berg determinations of the T_g of the alcohol-swollen sheets indicate that the transition in behaviour is not related to a thermal transition in the polymer, but rather to the generation of diffusional resistance in the high temperature penetration experiments which is comparable to the otherwise rate-determining Case II relaxations dominant in low temperature penetration. At high temperatures, the overall activation energy reflects the combination of diffusional absorption and the more highly activated relaxation-controlled transport. At low temperatures, diffusion of penetrant to the relaxing boundary is rapid compared with the slow, rate determining relaxations and, therefore, the concentration of penetrant is everywhere uniform within the already swollen shell. The extra-ordinarily high apparent activation energy describing the temperature dependence of the initial sorption rate at low temperature reflects the endothermic enthalpy of sorption of alcohols in PMMA as well as the strong coupling between relaxation rate and the penetrant concentration driving the rate determining relaxations. p]Clash—Berg measurements of the temperature dependence of the ten second shear moduli in partially swollen sheets, completely swollen sheets, and unswollen sheets suggest a T_g of approximatively 40°C in the alcohol-swollen PMMA. Moreover, an analysis of the Clash—Berg measurements suggests that the properties of the swollen regions of partially penetrated sheets are identical to the properties of the completely swollen sheets.     

Effect of Penetration Enhancers on Toenail Delivery of Efinaconazole from Hydroalcoholic Preparations

The incorporation of permeation enhancers in topical preparations has been recognized as a simple and valuable approach to improve the penetration of antifungal agents into toenails. In this study, to improve the toenail delivery of efinaconazole (EFN), a triazole derivative for onychomycosis treatment, topical solutions containing different penetration enhancers were designed, and the permeation profiles were evaluated using bovine hoof models. In an in vitro permeation study in a Franz diffusion cell, hydroalcoholic solutions (HSs) containing lipophilic enhancers, particularly prepared with propylene glycol dicaprylocaprate (Labrafac PG), had 41% higher penetration than the HS base. Moreover, the combination of hydroxypropyl-β-cyclodextrin with Labrafac PG further facilitated the penetration of EFN across the hoof membrane. In addition, this novel topical solution prepared with both lipophilic and hydrophilic enhancers was physicochemically stable, with no drug degradation under ambient conditions (25 °C, for 10 months). Therefore, this HS system can be a promising tool for enhancing the toenail permeability and therapeutic efficacy of EFN.     

Parallel factor analysis of HPLC-DAD data for binary mixtures of lidocaine and prilocaine with different levels of chromatographic separation

A set of 17 samples containing a constant amount of lidocaine (667 μM) and a decreasing amount of prilocaine (667-0.3 μM) was analysed by LC-DAD at three different levels of separation, followed by parallel factor analysis (PARAFAC) of the data obtained. In Case 1 no column was connected, the chromatographic resolution (R_s) therefore being zero, while Cases 2 and 3 had partly separated peaks (R_s=0.7 and 1.0). The results showed that in Case 1, analysed without any separation, the PARAFAC decomposition with a model consisting of two components gave a good estimate of the spectral and concentration profiles of the two compounds. In Cases 2 and 3, the use of PARAFAC models with two components resolved the underlying chromatographic, spectral and concentration profiles. The loadings related to the concentration profile of prilocaine were used for regression and prediction of the prilocaine content. The results showed that prediction of prilocaine content was possible with satisfactory prediction (RMSEP<0.01). This study shows that PARAFAC is a powerful technique for resolving partly separated peaks into their pure chromatographic, spectral and concentration profiles, even with completely overlapping spectra and the absence or very low levels of separation.     

Irradiation of Skin and Contrasting Effects on Absorption of Hydrophilic and Lipophilic Compounds

Increasing legal requirements for risk assessment and efficacy testing in the dermo-cosmetic field have led to the development of alternative test methods. In this study, the porcine skin model was chosen to test the effect of irradiation on the penetration habits of UV filters and caffeine. For decades, the pig has been recognized as an experimental animal in biomedical research thanks to its morphological and physiological similarities to humans. In this study, we wanted to investigate the effect of UV irradiation on the absorption of octocrylene (OC) and benzophenone-3 (B3) sunscreens used under those circumstances and a model hydrophilic molecule, caffeine (Caf). These particular compounds were chosen due to their different lipophilic profiles. The percutaneous penetration of the two UV filters and Caf was studied after two simulated solar radiation doses of 61.4 kJ m⁻². After irradiation simulation, the total absorbed dose was increased for OC while for B3 and Caf it was lower. Thus, modifications in percutaneous absorption have been observed, and it appears that UV could play a crucial role in this process. Moreover, it has been observed that the lipophilic profile of the studied compounds affects percutaneous penetration when irradiated.     

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (～7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from "pulling" coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives.     

Enhancing effect of pyrrolidone derivatives on transdermal penetration of phenolsulfonphthalein and indomethacin from aqueous vehicle

We investigated the enhancing effect of three alkyl-2-pyrrolidones on transdermal penetration of phenolsulfonphthalein (phenol red) and indomethacin from an aqueous vehicle by using an in vitro technique with excised rat skin. The enhancers included 1-methyl- (I), 1-hexyl- (II) and 1-lauryl-2-pyrrolidone (III). These derivatives effectively enhanced the penetration and skin accumulation of phenol red and indomethacin. Lipophilic enhancers such as II and III showed particularly high enhancing effects. The penetration profiles of phenol red and indomethacin showed a lag phase followed by a linear increase. Compounds II and III showed long lag times. The enhancer penetration was also determined. Compounds I and II showed a slight penetration. Compound III showed little penetration but high skin accumulation.     

Time-dependent excitation profiles for continuum Raman scattering

Time-dependent excitation profiles are calculated for a model system with a continuum of oscillator strength-carrying states. A simple procedure is suggested for relating absorption spectra with excitation profiles at all times based on a previously developed “reduced model” method.     

Development of a constant surface pressure penetration langmuir balance based on axisymmetric drop shape analysis

A new constant pressure pendant-drop penetration surface balance has been developed combining a pendant-drop surface balance, a rapid-subphase-exchange technique, and a fuzzy logic control algorithm. Beside the determination of insoluble monolayer compression-expansion isotherms, it allows performance of noninvasive kinetic studies of the adsorption of surfactants added to the new subphase onto the free surface and of the adsorption/penetration/reaction of the former onto/into/with surface layers, respectively. The interfacial pressure pi is a fundamental parameter in these studies: by working at constant pi one controls the height of the energy barrier to adsorption/penetration and can select different regimes and steps of the adsorption/penetration process. In our device a solution drop is formed at the tip of a coaxial double capillary, connected to a double microinjector. Drop profiles are extracted from digital drop micrographs and fitted to the equation of capillarity, yielding pi, the drop volume V, and the interfacial area A. pi is varied changing V (and hence A) with the microinjector. Control is based on a case-adaptable modulated fuzzy-logic PID algorithm able to maintain constant pi (or A) under a wide range of experimental conditions. The drop subphase liquid can be exchanged quantitatively by the coaxial capillaries. The adsorption/penetration/reaction kinetics at constant pi are then studied monitoring A(t), i.e., determining the relative area change necessary at each instant to compensate the pressure variation due to the interaction of the surfactant in the subsurface with the surface layer. A fully Windows-integrated program manages the whole setup. Examples of experimental protein adsorption and monolayer penetration kinetics are presented.     

A stochastic model in liquid penetration through fibrous media

The statistical genesis of the process of liquid penetration through fibrous media can be regarded as the interaction and the resulting balance among media and liquid cells that comprise the ensemble. A stochastic method, Ising's model, combined with Monte Carlo simulation, can therefore be employed in the study of liquid penetration through fibrous media. This process is driven by the difference of energy of the system after and before a liquid moves from one cell to the other. The energy of the system comprises the internal energy, work done by external force to the system, and the mechanical energy. For experimental verification, the process of water penetration through isotropic fiber mats, both spontaneously and under pressure, is examined. Simulation results are in good agreement with the experiments, indicating a good prospect of the method to be applied in this area.