Effect of Terpenes on the Enhancement of Skin Permeation of Lipophilic Drugs: A Systematic Review.

Objectives: The stratum corneum (SC) remains an obstacle to the passage of drugs applied topically. Several investigations have focused on enhancing the penetration of drugs through the SC by integrating permeation enhancers (PE) into the drug formulation. Terpenes are among the PE utilized in formulations and are categorized by the regulatory bodies as generally recognized as safe (GRAS). This study aimed to comparatively analyze the skin permeation enhancing effect of terpenes on lipophilic drugs. Methods: The present study reviewed the effects of terpenes on the permeation of lipophilic small-molecule drugs through the skin using original research published between 2000 - 2022 retrieved from PubMed®. The search phrase used was (lipophilic drug) AND (terpene) AND (permeation enhancer). Results: Terpenes increase the percutaneous permeation of lipophilic small molecule drugs by 1.06 - 256.80-fold. Linear correlation analysis of terpenes' cLog P with enhancement ratio (ER) revealed moderate and strong positive correlations in pig skin (r = 0.21) and mouse skin (r = 0.27), and rat skin (r = 0.41) and human skin (r = 0.67), respectively. Drug cLog P is a poor (r = -0.06) predictor of permeation enhancement. Terpenes with cLog P higher than 2.40 had ER greater than 10. Higher ERs (>30) were recorded for nerolidol, carvacrol, borneol, terpineol, limonene, menthone, pulegone, and menthol among the terpene-chemical penetration enhancers. Conclusion: cLog P of terpene-based chemical permeation enhancers (CPE) is strongly correlated with ER of lipophilic drugs across human skin. Non-polar groups in terpenes and hydrogen bond interactions by terpenes with SC lipid enhance cutaneous drug penetration of lipophilic drugs.

Development of an Auraptene-Loaded Transdermal Formulation Using Non-ionic Sugar Ester Surfactants.

Auraptene (Aur) is a naturally occurring monoterpene coumarin ether that exhibits numerous therapeutic properties. Its high lipophilicity and low skin penetration, however, limit its potential application for local and transdermal delivery. Biocompatible non-ionic sugar esters (SEs) possess beneficial properties for the development of transdermal formulations in delivering pharmaceutically challenging molecules such as graphene and Aur. In the present study, we conducted a series of experiments to demonstrate the effect of several previously unstudied SEs on the skin permeation and distribution of Aur by preparing gel- and dispersion-type formulations. Skin permeation and deposition experiments were conducted using a Franz diffusion cell with rat skin as the membrane. The dispersion-type formulations prepared using SEs had higher entrapment efficiency, as well as better skin permeation and retention profiles. The dispersion-type formulation containing sucrose palmitate (sSP) exhibited the highest skin permeation over 8 h. Notably, the enhancement effects on Aur concentration in full-thickness skin after the application of the dispersion-type formulation was higher than those of the control formulation. These results indicated that the prepared formulation has potential for use in the transdermal delivery of Aur in pharmaceutical and cosmetic products.

Preparation, Characterization, and In Vitro Evaluation of Inclusion Complexes Formed between S-Allylcysteine and Cyclodextrins.

The present study prepared inclusion complexes of S-allylcysteine (SAC) and cyclodextrin (α, ß, γ) by the freeze-drying (FD) method and verified the inclusion behavior of the solid dispersion. Also, the study investigated the effect of SAC/CD complex formation on liver tumor cells. Isothermal titration calorimetry (ITC) measurements confirmed the exothermic titration curve for SAC/αCD, suggesting a molar ratio of SAC/αCD = 1/1, but no exothermic/endothermic reaction was obtained for the SAC/ßCD and SAC/γCD system. Powder X-ray diffraction (PXRD) results showed that the characteristic diffraction peaks of SAC and CDs disappeared in FD (SAC/αCD) and FD (SAC/γCD), indicated by a halo pattern. On the other hand, diffraction peaks originating from SAC and ßCDs were observed in FD (SAC/ßCD). Near-infrared (NIR) absorption spectroscopy results showed that CH and OH groups derived from SAC and OH groups derived from αCD and γCD cavity were shifted, suggesting complex formation due to intermolecular interactions occurring in SAC/αCD and SAC/γCD. Stability test results showed that the stability was maintained with FD (SAC/αCD) over FD (SAC/ßCD) and FD (SAC/γCD). In 1H-1H of NOESY NMR measurement, FD (SAC/αCD) was confirmed to have a cross peak at the CH group of the alkene of SAC and the proton (H-3, -5, -6) in the αCD cavity. In FD (SAC/γCD), a cross peak was confirmed at the alkyl group on the carbonyl group side of SAC and the proton (H-3) in the cavity of γCD. From the above, it was suggested that the inclusion mode of SAC is different on FD (SAC/CDs). The results of the hepatocyte proliferation inhibition test using HepG2 cells showed that FD (SAC/ßCD) inhibited cell proliferation. On the other hand, FD (SAC/αCD) and FD (SAC/γCD) did not show a significant decrease in the number of viable cells. These results suggest that the difference in the inclusion mode may contribute to the stability and cell proliferation inhibition.

Preparation and Spectroscopic Characterization of Inclusion Complexes of 3D Ball-Milled Rifampicin with ß-cyclodextrin and γ-cyclodextrin : 3D Ball-Milled Rifampicin with ß-cyclodextrin and γ-cyclodextrin.

Rifampicin (RFP) solutions, intended to reduce incidence of prosthetic graft infection, were prepared as three-dimensional ground mixtures (3DGMs) using ß-cyclodextrin (ßCD) and γ-cyclodextrin (γCD) and characterized for their spectroscopic properties and solubility. Phase solubility diagrams revealed that 3DGMs (RFP/ßCD and RFP/γCD) produced a complex at 1:1 molar ratio. Pulsed field gradient nuclear magnetic resonance experiments indicated that the diffusion coefficients for RFP/ßCD and RFP/γCD were similar to the respective diffusion coefficients for ßCD and γCD. Rotating-frame Overhauser effect spectroscopy NMR spectra revealed the existence of a new exchanger peak for RFP/γCD, suggesting an intermolecular interaction different from that of RFP/ßCD. Differential scanning calorimetry confirmed the presence of endothermic peak at 191 °C indicating the manifestation of RFP in the inclusion complex. Interestingly, molecular interactions from the complexes, RFP/ßCD and RFP/γCD, revealed different patterns of inclusion in the 3DGMs. In RFP/ßCD, nuclear Overhauser effect spectroscopy NMR spectra indicated cross peaks for the protons of the methyl group of RFP and the protons (H-5 and H-6) in the ßCD cavity. The methyl group of RFP interacted with the narrow rim of ßCD. With RFP/γCD, cross peaks were due to the protons of the methyl group of RFP and the protons of the cavity of γCD suggesting multiple inclusion patterns. The observed multiple cross peaks affirm the inclusion of RFP into the CD cavity which enhanced its solubility by 1.6-2.0-fold when prepared as 3DGMs as RFP/ßCD and RFP/γCD, respectively.

Preparation, Characterization, Solubility, and Antioxidant Capacity of Ellagic Acid-Urea Complex.

Ellagic acid (EA), a natural polyphenol found in berries, has high antioxidant capacity. This study aimed to improve EA solubility by complex formation with urea (UR) using solvent evaporation method and evaluate its solubility, antioxidant capacity, and physical properties. The solubility test (25 °C, 72 h) showed that the solubility of EVP (EA/UR = 1/1) was approximately two-fold higher than that of EA (7.13 µg/mL versus 3.99 µg/mL). Moreover, the IC50 values of EA and EVP (EA/UR = 1/1) (1.50 µg/mL and 1.30 µg/mL, respectively) showed higher antioxidant capacity of EVP than that of EA. DSC analysis revealed that the UR peak at 134 °C disappeared, and a new endothermic peak was observed at approximately 250 °C for EVP (EA/UR = 1/1). PXRD measurements showed that the characteristic peaks of EA at 2θ = 12.0° and 28.0° and of UR at 2θ = 22.0°, 24.3°, and 29.1° disappeared and that new peaks were identified at 2θ = 10.6°, 18.7°, and 26.8° for EVP (EA/UR = 1/1). According to 2D NOESY NMR spectroscopy, cross-peaks were observed between the -NH and -OH groups, suggesting intermolecular interactions between EA and UR. Therefore, complexation was confirmed in EA/UR = 1/1 prepared by solvent evaporation, suggesting that it contributed to the improvement in solubility and antioxidant capacity of EA.

Preparation and Characterization of a Hybrid Complex of Cyclodextrin-Based Metal-Organic Frameworks-1 and Ascorbic Acid Derivatives.

Cyclodextrin-based metal-organic frameworks-1 (CD-MOF-1) prepared using potassium hydroxide, ethanol, and γ-cyclodextrin (γ-CD) has been reported as a new type of MOF for the development of pharmaceutical formulations. The present study aimed to investigate the physicochemical properties of ascorbic acid derivatives (L-ascorbyl 6-palmitate (ASCP); L-ascorbyl 2,6-palmitate (ASCDP)) complexed with CD-MOF-1 by a solvent evaporation method. Powder X-ray diffraction revealed that the crystal diffraction pattern of CD-MOF-1 changed from α-type to ß-type when prepared by a solvent evaporation method. For ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4 evaporated samples, the crystal diffraction peaks derived from ASCP and ASCDP disappeared, indicating a ß-like behavior. Differential scanning calorimetry results revealed that the endothermic peaks of evaporated samples (ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4) were not detected due to melting. Furthermore, intermolecular interactions were observed in the hydrogen bonds between the CH groups of the side chains of ASCP and ASCDP and the OH group of CD-MOF-1 in (ASCP/CD-MOF-1 = 1/2) and EVP (ASCDP/CD-MOF-1 = 1/4), based on the near-infrared absorption spectroscopy analysis. CD-MOF-1 did not form inclusion complexes with the lactone rings of ASCP and ASCDP, but with the lipophilic side chains. These results suggested that CD-MOF-1 may be useful in preparing novel drug carriers for ASCP and ASCDP.

Inclusion Complexes of Daidzein with Cyclodextrin-Based Metal-Organic Framework-1 Enhance Its Solubility and Antioxidant Capacity.

Daidzein, an aglycone-type isoflavone, is useful in the prevention of atherosclerotic cardiovascular diseases. However, the solubility of daidzein remains relatively low even with pharmaceutical interventions (e.g., γ-cyclodextrin inclusion complex). In the present study, daidzein-cyclodextrin-metal organic framework solid dispersion complexes were prepared by the solvent evaporation method. The physicochemical properties of the complex and its effect on the solubility of daidzein were evaluated. The enhancement effect of a cyclodextrin-metal organic framework on the antioxidant properties of daidzein was verified using a diphenyl-picrylhydrazyl radical scavenging test. Powder X-ray diffraction results showed that the characteristic diffraction peaks of daidzein and cyclodextrin-metal organic framework disappeared and new peaks (2θ = 7.1°, 16.5°) were observed. FT-IR measurements showed that the peak derived from the carbonyl group of daidzein shifted to the lower wavenumber. NOESY 1H-1H NMR showed cross peaks at the proton on the resorcinol side of daidzein and the proton (H-5, H-6) in a cyclodextrin-metal organic framework. Dissolution rate of daidzein at 5 min in distilled water was 0.06% for daidzein alone while the daidzein inclusion complex was about 100%. When fasted state simulated intestinal fluid was used, the dissolution rate of the daidzein complex was about 71% compared with that of daidzein alone (~ 3.0%) at 5 min. The daidzein inclusion complex improved the antioxidant capacity to ~ 1.3 times (17.8 µg/mL) compared to the IC50 of daidzein alone (22.9 µg/mL). Preparations of cyclodextrin-metal organic framework inclusion complexes will be a platform in developing pharmaceutical formulations to enhance the bioavailability and activity of drugs.

Prolonged Distribution of Tranilast in the Eyes after Topical Application onto Eyelid Skin.

Tranilast, a lipophilic drug with various ophthalmic applications, was used as a model drug to establish the possibility of delivering lipophilic drugs through the eyelid skin. Pharmacokinetics and tissue distribution studies were conducted employing three application methods (topical application onto eyelid skin, eye drops, and intravenous injection in rats) to broaden the significance of delivering drugs through the eyelids. A two-compartment open model analysis was used for intravenous route while a non-compartmental evaluation was used for topical applications to estimate the pharmacokinetic parameters. Eyelid skin application, eye drops, and intravenous administration had mean residence times (MRTs) of 8.07, 1.79, and 3.25 h in the eyeball and 10.8, 1.29, and 2.97 h in the conjunctiva, correspondingly. In the eyeball, topical application of tranilast onto the eyelids corresponded to a 4.5- and 2.5-fold higher MRT compared with eye drops and intravenous administration, respectively. An 8.4- or 3.6-fold higher MRT was observed in the conjunctiva after topical application compared with eye drops or intravenous administration, respectively. This indicated a gradual penetration of tranilast into the eyeball and conjunctiva, subsequently a slow elimination from these target tissues.

Enhanced nose-to-brain delivery of tranilast using liquid crystal formulations.

Intranasal administration is poised as a competent method in delivering drugs to the brain, because the nasal route has a direct link with the central nervous system bypassing the formidable blood-brain barrier. C17-monoglycerol ester (MGE) and glyceryl monooleate (GMO) as liquid crystal (LC)-forming lipids possess desirable formulation characteristics as drug carriers for intranasally administered drugs. This study investigated the effect of LC formulations on the pharmacokinetics of tranilast (TL), a lipophilic model drug, and its distribution in the therapeutic target regions of the brain in rats. The anatomical biodistribution of LC formulations was monitored using micro-computed tomography tandem in vivo imaging systems. MGE and GMO effectively formed LC with suitable particle size, zeta potential, and viscosity supporting the delivery of TL to the brain. MGE and GMO LC formulations enhanced brain uptake by 10- to 12-fold and 2- to 2.4- fold, respectively, compared with TL solution. The olfactory bulb had the highest TL concentration and fluorescent signals among all the brain regions, indicating a direct nose-to-brain delivery pathway of LC formulations. LC-forming lipids, MGE and GMO, are potential biomaterials in formulations intended for intranasal administration.

Prediction of skin permeation and concentration of rhododendrol applied as finite dose from complex cosmetic vehicles.

Finite dose experiments represent clinical use wherein depletion of dose, evaporation of excipients, and gradual change in vehicle composition may occur. In the present study, we attempted a mathematical approach for predicting skin permeation and concentration of a cosmetic active, rhododendrol (RD), from complex vehicle-based formulations applied in finite dose. In vitro skin permeation and concentration studies of RD were conducted from formulations containing water and polyols with concentrations ranging from 10 to 100% under infinite and finite dose conditions using vertical Franz diffusion cells. Observed data for skin permeation and the viable epidermis and dermis (VED) concentration of RD were estimated by the differential equations under Fick's second law of diffusion together with water evaporation kinetics and changes in the partition coefficient from vehicles to the stratum corneum. As a result, a goodness-of-fit was observed allowing accurate estimation of skin permeation and VED concentration of RD. This mathematical approach could become a useful tool to estimate the skin permeation and concentration of actives from topical formulation applied in finite dose conditions likened in actual use.

Usefulness of Artificial Membrane, Strat-M®, in the Assessment of Drug Permeation from Complex Vehicles in Finite Dose Conditions.

The ban on the use of animals in testing cosmetic products has led to the development of animal-free in vitro methods. Strat-M® is an artificial membrane engineered to mimic human skin and is recommended as a replacement for skin. However, its usefulness in the assessment of the permeation of cosmetics in in-use conditions remains unverified. No data have been published on its comparative performance with the membrane of choice, porcine skin. The comparative permeability characteristics of Strat-M® and porcine skin were investigated using Franz diffusion cells. Caffeine (CF) and rhododendrol (RD) in complex vehicles with varying concentrations of polyols were applied as finite and infinite doses. Good rank orders of permeation from finite dose experiments were observed for RD. High correlations were observed in RD permeation between Strat-M® and porcine skin under finite and infinite dose conditions, whereas only finite dose conditions for CF were associated with good correlations. Permeation from formulations with high polyol content and residual formulations was enhanced due to the disruption of the integrity of the Strat-M® barrier. The usefulness of Strat-M® in the assessment of dermal permeation may be limited to finite dose conditions and not applicable to infinite dose conditions or formulations applied in layers.

Effect of layered application on the skin permeation of a cosmetic active component, rhododendrol.

Cosmetics containing rhododendrol (RD) were voluntarily recalled after incidents of leukoderma related to their use. Users reported using up to five different RD-containing products by layered application. In this study, we investigated the effects of layered application, formulations, and their components on the skin permeation of cosmetics containing RD. Experiments were designed to simulate actual in-use conditions, such as varying application volumes, physical mixing of formulations, sequence of cosmetics application and time interval between applications, to establish their effect on the skin permeation of RD. Milk and lotion RD-containing cosmetics (2%), 1% aqueous RD, and preparations of formulation components were applied as the first or second layers as finite doses of 10 or 20 µL/cm2. Permeation experiments were performed through excised porcine ear skin using Franz diffusion cells with an effective diffusion area of 1.77 cm2. Cosmetics applied by layered application exhibited lower skin permeation of RD compared with a single application despite having the same application dose. High initial volume (20 µL at 0 or 5 sec) did not exhibit any significant reduction in the permeation of RD. Formulations and their components caused varying reductions in RD permeation, probably due to changes in thermodynamic activity of the active component. Layered application, formulation components, application volume, time interval and sequence of application had significant influences on the skin permeation of the active component. Moreover, this study established a method of investigating the influence of formulations and their components on the skin permeation of actives after layered application.

Modeling oxyanion adsorption on ferralic soil, part 1: parameter validation with phosphate ion.

Surface complexation models have proved to be valuable tools for predicting processes that occur at the solid-solution interface. Use of such models has become more widespread and nowadays more complex systems are studied, in an attempt to explain processes such as the competition between different species for mineral surfaces and the effect of the presence of organic matter. The aim of the present study was to analyze the mobility of phosphate in ferralic soils. The charge distribution model parameters for phosphate-goethite adsorption were used to predict phosphate mobility on samples from 2 horizons of a ferralic soil containing large amounts of iron oxides. The soil reactivity was attributed to the iron oxides, and some specific parameters were determined by means of phosphate adsorption-desorption experiments and included in the model. Adsorption of phosphate in the upper horizon, which contained more organic carbon and phosphate than the deeper one, was modeled by using the information obtained for the soil and the charge distribution model parameters derived for phosphate-goethite interaction with no need of further optimization. In contrast, some extra fitting parameters were required to improve the modeling of the phosphate adsorption in the deeper horizon.

Modeling oxyanion adsorption on ferralic soil, part 2: chromate, selenate, molybdate, and arsenate adsorption.

High levels of oxyanions are found in the soil environment, often as a result of human activity. At high concentrations, oxyanions can be harmful to both humans and wildlife. Information about the interactions between oxyanions and natural samples is essential for understanding the bioavailability, toxicity, and transport of these compounds in the environment. In the present study, the authors investigated the reactivity of different oxyanions (AsO4 , MoO4 , SeO4 , and CrO4 ) at different pH values in 2 horizons of a ferralic soil. By combining available microscopic data on iron oxides with the macroscopic data obtained, the authors were able to use the charge distribution model to accurately describe the adsorption of these 4 oxyanions and thus to determine the surface speciation. The charge distribution model was previously calibrated and evaluated using phosphate adsorption/desorption data. The adsorption behavior on ferralic soil is controlled mainly by the natural iron oxides present, and it is qualitatively analogous to that exhibited by synthetic iron oxides. The highest adsorption was found for arsenate ions, whereas the lowest was found for selenate, with chromate and molybdate ions showing an intermediate behavior.

Effect of organic matter and pH on the adsorption of metalaxyl and penconazole by soils.

Soil organic matter (SOM) is considered to be the primary adsorbent of non-ionic pesticides, and it is therefore thought to determine the concentration of such pesticides in the soil solution and how they are transported throughout the medium. It is generally assumed that the sorption capacity of different soils is the same per unit mass of SOM; however, the reactivity also depends on the SOM composition and the pH of the medium. We carried out experiments to study the effects of pH and ionic strength on the adsorption of the non-ionic fungicides metalaxyl and penconazole on four soils containing different amounts of organic carbon. The adsorption isotherms fitted a Freundlich equation. For pH>5, partitioning of the fungicides between the solid phase and the soil solution did not vary with the pH, while at lower pH, the fraction adsorbed on the solid phase increased as the pH decreased. The response was related to the effect of pH on the ionization of the carboxylic groups of the SOM and therefore to the hydrophilic nature of the SOM. Analysis of the charge effect on the partitioning of both fungicides revealed a common response in all four soils. Adsorption appears to be related to the magnitude of the charge developed at the SOM due to ionization of the carboxylic acid groups.

Comparison of arsenate, chromate and molybdate binding on schwertmannite: surface adsorption vs anion-exchange.

The presence of iron oxides may play an important role in controlling the mobility and availability of contaminants in soils and waters affected by acid mine drainage. The present study describes the uptake of arsenate, chromate and molybdate from solution by synthetic schwertmannite. Batch experiments were performed at different pH values in order to obtain the adsorption isotherms for the three oxyanions. In addition to the formation of surface complexes between the oxyanions and the iron surface reactive groups, it is also expected that anion exchange will occur between sulphate anions from the schwertmannite structure and the oxyanions present in the solid/solution interface. Comparison of the experimental adsorption results for the different oxyanions showed large differences, not only the amount adsorbed, which was much higher for arsenate, but also in the sulphate exchange with the anions in solution. In case of chromate, the main mechanism of adsorption process is the exchange reaction with the sulphate groups present in the schwertmannite. The observed results suggest a different adsorption mechanisms for each of the three oxyanions, with important implications for the mobility of these anions in acid mine drainage systems.

Adsorption of paraquat on soil organic matter: effect of exchangeable cations and dissolved organic carbon.

Herbicides that interact with soil organic matter do so with both the solid and the dissolved fractions, so that the distribution of herbicide between the soil solution and solid phases is determined by competitive effects. In the present study, adsorption experiments were carried out with the cationic herbicide paraquat and untreated and acid-washed samples of a peat soil, at different values of pH and ionic strength. Less herbicide was adsorbed onto the untreated peat than onto the acid-washed peat; the difference was due to the presence of exchangeable cations, as demonstrated in experiments carried out by adding Ca(2+) to suspensions of acid-washed peat. The results were interpreted by an electrostatic model and the fitting parameters indicated that the adsorption constants were the same for both samples of peat, although the number of binding sites available was different. Simultaneous resolution of the adsorption equilibrium of paraquat for the soil organic matter (SOM) and of the binding equilibrium between paraquat and dissolved organic matter (DOM) enabled the distribution of paraquat between the solid and solution phases to be determined. The increased solubility of the SOM with increasing pH led to a decrease in the fraction of paraquat retained on the peat surface above pH 5.5, which favors the mobility of the herbicide in the soil.

Adsorption of paraquat on goethite and humic acid-coated goethite.

Adsorption of cationic pesticides in soils is generally attributed to mineral clays and organic matter components. However, iron oxides may also contribute to such adsorption or affect it by associating with other components. Using goethite and humic acid as models for iron oxides and organic matter respectively, we studied the adsorption of the cationic pesticide paraquat on goethite and humic acid-coated goethite. At pH 4.0 the adsorption on goethite was not significant, and at pH 10.0, although the surface of the oxide was negatively charged, much less pesticide was adsorbed than on mineral clays. At this pH the adsorption of paraquat decreased as the ionic strength increased, and application of the charge distribution multisite complexation model (CD-MUSIC model) enabled interpretation of the results. At pH 4, the adsorption of paraquat on the humic acid-coated goethite was similar to the adsorption on mineral clays, but was considerably less than the adsorption on humic acid in solution. The lower adsorption on solid organic matter is attributed to a decrease in the number of "active" binding sites on the humic acid as a result of the binding to iron oxide.

Analysis of phosphate adsorption onto ferrihydrite using the CD-MUSIC model.

Ferrihydrite nanoparticles may dominate the ion binding properties of the natural oxide fraction present in soil and aquatic systems. A correct description of the adsorption properties of ferrihydrite nanoparticles may be useful for gaining a better insight into the adsorption processes in natural systems and at the same time will be essential for developing surface complexation models able to describe these processes. In the present study, phosphate speciation in ferrihydrite has been analyzed combining the available spectroscopic data and molecular information with modeling calculations. For this purpose, a new data set that analyzes the effect of pH and ionic strength on the phosphate adsorption onto ferrihydrite has been used. Description of the phosphate adsorption process onto ferrihydrite nanoparticles, for the entire pH and ionic strength range, has been made taking into account the presence of protonated and nonprotonated bidentate surface complexes. The presence of monodentate complexes, protonated and nonprotonated, was also analyzed, but no significant improvement in the description of the results was observed. The surface complexation constants obtained with the CD-MUSIC modeling calculations are comparable to the values found in the literature for phosphate surface complexes in goethite particles.

Copper binding by peat fulvic and humic acids extracted from two horizons of an ombrotrophic peat bog.

We studied the binding of Cu(II) to humic acids and fulvic acids extracted from two horizons of an ombrotrophic peat bog by metal titration experiments at pH 4.5, 5.0, 5.5, and 6.0 and 0.1 M KNO3 ionic strength. Free metal ion concentrations in solution were measured using an ion selective electrode. The amounts of base required to maintain constant pH conditions were recorded and used to calculate H+/Cu2+ exchange ratios. The amount of Cu(II) bound to the humic fractions was greater than the amount bound to the fulvic fractions and only at the highest concentrations of metal ion the amount of Cu(II) sorbed by both fractions became equal. The proton to metal ion exchange ratios are similar for all humic substances, with values ranging from 1.0 to 2.0, and decreasing with increased pH. The amount of Cu(II) bound is practically independent of the horizon from which the sample was extracted. The results indicate that the humic substances show similar cation binding behaviour, despite the differences in chemical composition. The copper binding data are quantitatively described with the NICA-Donnan model, which allows to characterize only the carboxylic type binding sites. The values of the binding constants are higher for the humic acids than for the fulvic acids.