Academic literature on the topic 'Physicochemical model'

The present study was aimed to investigate the relationships between permeability and membrane retention values (logPe and MR) of the in vitro non-cellular permeability assay, corneal-PAMPA in comparison with experimental Caco-2 permeability data and calculated physicochemical properties (MW, clogP, clogD7.4 , TPSA). For the investigation, 50 structurally and physicochemically diverse drugs were selected and measured in PAMPA model optimized for corneal permeability. The results showed corneal-PAMPA model's orthogonality in terms of passive diffusion to the FDA approved Caco-2 as a gastrointestinal absorption model, while the comparison with physicochemical properties revealed trends between logPe , MR and the lipophilicity descriptors and TPSA.

We present a general physicochemical sampling model for olfaction, based on established pharmacological laws, in which arbitrary combinations of odorant ligands and receptors can be generated and their individual and collective effects on odor representations and olfactory performance measured. Individual odor ligands exhibit receptor-specific affinities and efficacies; that is, they may bind strongly or weakly to a given receptor, and can act as strong agonists, weak agonists, partial agonists, or antagonists. Ligands interacting with common receptors compete with one another for dwell time; these competitive interactions appropriately simulate the degeneracy that fundamentally defines the capacities and limitations of odorant sampling. The outcome of these competing ligand-receptor interactions yields a pattern of receptor activation levels, thereafter mapped to glomerular presynaptic activation levels based on the convergence of sensory neuron axons. The metric of greatest interest is the mean discrimination sensitivity, a measure of how effectively the olfactory system at this level is able to recognize a small change in the physicochemical quality of a stimulus. This model presents several significant outcomes, both expected and surprising. First, adding additional receptors reliably improves the system’s discrimination sensitivity. Second, in contrast, adding additional ligands to an odor scene initially can improve discrimination sensitivity, but eventually will reduce it as the number of ligands increases. Third, the presence of antagonistic ligand-receptor interactions produced clear benefits for sensory system performance, generating higher absolute discrimination sensitivities and increasing the numbers of competing ligands that could be present before discrimination sensitivity began to be impaired. Finally, the model correctly reflects and explains the modest reduction in odor discrimination sensitivity exhibited by transgenic mice in which the specificity of glomerular targeting by primary olfactory neurons is partially disrupted.

AbstractIt is an important issue to calculate the physicochemical properties of aluminosilicate melt based on some known data. However, it is also a difficult issue to do so, especially for a multicomponent slag system since the available data are very limited due to the difficulty of experimental measurement at high temperature. In this paper, a method is suggested to resolve this problem, which is particularly significant. This model can be well used to estimate the electrical conductivity, viscosity, molar volume and surface tension of aluminosilicate melt.

Increased and combined knowledge of food processing, molecular biology, health and nutrition has triggered production of many different types of functional foods and pharmaceutics recently. The efficacy and safety of such products are being assessed prior to marketing by in vivo and/or in vitro studies. Traditional in vivo studies require excessive time, cost and labour, as well as ethical approvals with subject to humans or animals in some instances. Therefore excessive number of runs may be avoided if reliable in vitro system is available. During the course of this study, an in vitro physicochemical upper gastrointestinal tract system (IPUGS), the first of its kind in literature, has been developed to simulate the relevant conditions of the gastrointestinal tract (GIT) as closely as possible to the human physiology with multi-disciplinary approach, combining biology, physiology, gastroenterology, process technology, chemical engineering and automation. The IPUGS is aimed at having a high predictive capability towards the real digestion processes occurring in the human upper GIT which allows for examining of the bioavailability of nutrients and drugs, drug-nutrient interactions, viability of probiotics and case studies of gastrointestinal disorders. Digestion of rice and baby foods have been studied with the IPUGS by UV-spectrophotometer, HPLC, light microscope and pH meter under the conditions of normal state and common gastric disorders, such as gastroparesis, dumping syndrome, Zollinger-Ellison syndrome and hypochlorhydria. By comparing the data from many physiological and clinical sources in the literature, it would seem that the IPUGS was able to generate more reliable data compared to the existing in vitro digestion (mechanical) models in the literature. In future, computer-controlled and computer-recorded data by possibly designing a new software or equations would be desirable to implicate a better understanding of the digestive processes.

Ce travail s'inscrit dans un but de caractérisation et de quantification des propriétés physiques et chimiques de la matière vivante et de ses constituants. Les objectifs recherches sont de deux ordres: une meilleure compréhension des mécanismes d'interaction des ondes ultrasonores avec les milieux biologiques, qui sont parmi les plus complexes; le développement de méthodes ultrasonores permettant de mesurer des propriétés physico-chimiques des milieux biologiques. Le choix des glucides comme modèle moléculaire pour étudier l'interaction ultrasons-milieux biologiques réside dans le fait que ces molécules sont d'une importance fondamentale dans la composition des structures vivantes au même titre que les protéines et les lipides. De plus, elles forment un groupe comprenant des isomères et des polymères plus ou moins complexes. L’influence de la structure moléculaire est accessible en examinant l'atténuation, la vitesse et les effets non linéaires. L’analyse de ces divers paramètres est menée dans une gamme de fréquence ultrasonore située entre 50 et 200 mhz, par une technique acousto-optique.

Doctor of Philosophy
Department of Grain Science and Industry
Praveen V. Vadlani
The purpose of this study was to investigate micro- and macro-scale aspects of solid state fermentation (SSF) for production of cellulolytic enzymes using fungal cultures. Included in the objectives were investigation of effect of physicochemical characteristics of substrate on enzymes production at micro-scale, and design, fabrication and analysis of solid-state bioreactor at macro-scale. In the initial studies response surface optimization of SSF of soybeans hulls using mixed culture of Trichoderma reesei and Aspergillus oryzae was carried out to standardize the process. Optimum temperature, moisture and pH of 30ºC, 70% and 5 were determined following optimization. Using optimized parameters laboratory scale-up in static tray fermenter was performed that resulted in production of complete and balanced cellulolytic enzyme system. The balanced enzyme system had required 1:1 ratio of filter paper and beta-glucosidase units. This complete and balanced enzyme system was shown to be effective in the hydrolysis of wheat straw to sugars. Mild pretreatments– steam, acid and alkali were performed to vary physicochemical characteristics of soybean hulls – bed porosity, crystallinity and volumetric specific surface. Mild nature of pretreatments minimized the compositional changes of substrate. It was explicitly shown that more porous and crystalline steam pretreated soybean hulls significantly improved cellulolytic enzymes production in T. reesei culture, with no effect on xylanase. In A. oryzae and mixed culture this improvement, though, was not seen. Further studies using standard crystalline substrates and substrates with varying bed porosity confirmed that effect of physicochemical characteristics was selective with respect to fungal species and cellulolytic activity. A novel deep bed bioreactor was designed and fabricated to address scale-up issues. Bioreactor’s unique design of outer wire mesh frame with internal air distribution and a near saturation environment within cabinet resulted in enhanced heat transfer with minimum moisture loss. Enzyme production was faster and leveled within 48 h of operation compared to 96 h required in static tray. A two phase heat and mass transfer model was written that accurately predicted the experimental temperature profile. Simulations also showed that bioreactor operation was more sensitive to changes in cabinet temperature and mass flow rate of distributor air than air temperature.

In the present thesis, the correlation between the physicochemical and antigenic properties of different recombinant Streptococcus gordonii vaccine vectors was studied. Evaluation of vaccine efficacy, antigenicity and immugenicity is a crucial step in developing vaccines, thus investigating a simple method to analyze vaccine efficacy besides other methods could be a major part of developing bacterial vaccine vectors. To approach this, isoelectric point measurements and zeta-potential titration as well as antigenicity and immunogenicity of S.gordonii vaccine vectors (with fbpA, RPS, gtfg genes mutations expressing H1 antigen) were used. These data showed that strains with more positive surface charge had higher heterologous antigen recognition and lower antibody responses in the serum of immunized mice. This correlation between surface charge and antigenicity and immunogenicity revealed the importance of using simple methods such as zeta potential titration and isoelectric point measurements to predict engineered vaccine vectors antigenicity and possible efficacy. In the second part of the thesis the immune recall in the days following Streptococcus pneumoniae lung infection by transcriptomic analysis was studied. S. pneumoniae is the most common bacterial cause of community-acquired pneumonia. Host-pathogen interaction is poorly understood, and factors that drive a more severe phenotype are unknown. One way to study host response to pathogen is using the stimulation of immune system cells with live or killed bacteria. We combined transcriptomic and cytokine level analysis on stimulated mouse splenocytes revealing the presence of a recall immune response involving both innate and adaptive immunity, stronger from the fourth day after infection. This model could analyze immune responses involved in pneumococcal infection as well as vaccine and experimental therapies efficacy in future studies. Finally, the development of a S. pneumoniae mouse model of pneumonia by intra-tracheal infection was set up. The nasopharynx of humans is the only natural reservoir for the pneumococci. To mimic human pneumonia, mice models are widely used. Bacteria can be administered to mice intranasally, intratracheally or as aerosols. Pneumococcal pneumonia was induced in mice by intra-tracheal inoculation with different doses of S. pneumoniae TIGR4. Data showed high colonization of bacteria in lung, liver and spleen starting 24 hours post-infection. Pneumonia mortalities were observed in all mice infected by 108 within 24 hours of infection. Further analysis should be done to investigate the host-pathogen interaction as well as vaccine and experimental therapies efficacy by using this model.

A pharmaceutical dosage form is an entity that is administered to patients so that they receive an effective dose of an active pharmaceutical ingredient (API). The proper design and formulation of a transdermal dosage form require a thorough understanding of the physiological factors affecting percutaneous penetration and physicochemical characteristics of the API, as well as that of the pharmaceutical exipients that are used during formulation. The API and pharmaceutical excipients must be compatible with one another to produce a formulation that is stable, efficacious, attractive, easy to administer, and safe (Mahato, 2007:11). Amongst others, the physicochemical properties indicate the suitability of the type of dosage form, as well as any potential problems associated with instability, poor permeation and the target site to be reached (Wells & Aulton, 2002:337). Therefore, when developing new or improved dosage forms, it is of utmost importance to evaluate the factors influencing design and formulation to provide the best possible dosage form and formulation for the API in question. Delivery of an API through the skin has long been a promising concept due to its large surface area, ease of access, vast exposure to the circulatory and lymphatic networks, and non-invasive nature of the therapy. This is true whether a local or systemic pharmacological effect is desired (Aukunuru et al., 2007:856). However, most APIs are administered orally as this route is considered to be the simplest, most convenient and safest route of API administration. Since ibuprofen is highly metabolised in the liver and gastrointestinal tract, oral administration thereof results in decreased bioavailability. Furthermore, it also causes gastric mucosal damage, bleeding and ulceration. Another obstacle associated with oral API delivery is that some APIs require continuous delivery which is difficult to achieve (Bouwstra et al., 2003:3). Therefore, there is significant interest to develop topical dosage forms for ibuprofen to avoid side effects associated with oral delivery and to provide relatively consistent API levels at the application site for prolonged periods (Rhee et al., 2003:14). The aim of this study was to determine the influence of selected formulation factors on the transdermal delivery of ibuprofen. In order to achieve this aim, the physicochemical properties of ibuprofen had to be evaluated. The aqueous solubility, pH-solubility profile, octanol-water partition coefficient (log P-value) and octanol-buffer distribution coefficient (log D-values, pH 5 and 7.4) of ibuprofen were determined. According to Naik et al., (2000:319) the ideal aqueous solubility of APIs for transdermal delivery should be more than 1 mg.ml-1. However, results showed that ibuprofen depicted an aqueous solubility of 0.096 mg.ml-1 ± 25.483, which indicated poor water solubility and would therefore be rendered less favourable for transdermal delivery if only considering the aqueous solubility. The pH-solubility profile depicted that ibuprofen was less soluble at low pH-values and more soluble at higher pH-values. Previous research indicated that the ideal log Pvalues for transdermal API permeation of non steroid anti-inflammatory drugs (NSAIDs) are between 2 and 3 (Swart et al., 2005:72). Results obtained during this study indicated a log P-value of 4.238 for ibuprofen. This value was not included in the ideal range, which is an indication that the lipophilic/hydrophilic properties are not ideal, and this might therefore; contribute to poor ibuprofen penetration through the skin. Furthermore, the obtained log D-values at pH 5 and 7.4 were 3.105 and 0.386, respectively. Therefore, it would be expected that ibuprofen incorporated into a formulation prepared at a pH of 5 would more readily permeate the skin compared to ibuprofen incorporated into a formulation prepared at a pH of 7.4. A gel, an emulgel and a Pheroid™ emulgel were formulated at pH 5 and 7.4, in order to examine which dosage form formulated at which pH would deliver enhanced transdermal delivery. Obtained diffusion results of the different semi-solid formulations were furthermore compared to a South African marketed commercial product (Nurofen® gel) in order to establish if a comparable formulation could be obtained. An artificial membrane was used to conduct the membrane permeation studies over a period of 6 h, in order to determine whether ibuprofen was in fact released from the formulations through the membrane. Skin permeation studies were conducted using Franz diffusion cells over a period of 12 h where samples were withdrawn at specified time intervals. All the formulations exhibited an increase in the average cumulative amount of ibuprofen released from the formulations and that permeated the membrane when compared to Nurofen® gel. This increase was statistically significant (p<0.05) for the gel, emulgel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest cumulative amount of ibuprofen that permeated the membrane. Preparations formulated at a pH of 5, did not differ significantly from Nurofen® when the average cumulative amount of ibuprofen that permeated the membrane were compared. The following rank order for the average cumulative amount released from the formulations could be established: Gel (pH 7.4) >>>> Pheroid™ emulgel (pH 7.4) > Emulgel (pH 7.4) >>> Gel (pH 5)> Pheroid™ emulgel (pH 5) ≈ Emulgel (pH 5) > Nurofen® gel. On the other hand, all the formulations exhibited an increase in the average cumulative amount of ibuprofen that permeated the skin when compared to Nurofen® gel. This increase was statistically significant (p < 0.05) for the gel, emulgel and Pheroid™ emulgel at pH 5, as well as the emulgel and Pheroid™ emulgel at pH 7.4. The emulgel at pH 5 exhibited the highest cumulative amount of ibuprofen that permeated the skin. The following rank order for the average cumulative amount released from the formulations and that permeated the skin could be established: Emulgel (pH 5) >> Pheroid™ emulgel (pH 5) > Gel (pH 5) > Emulgel (pH 7.4)> Pheroid™ emulgel (pH 7.4) ≈ Emulgel (pH 7.4) >> Nurofen® gel > Gel (pH 7.4). From this rank order it was clear that a trend was followed where the pH of formulation also played a role in ibuprofen permeation. All the formulations exhibited a higher release rate and flux when compared to Nurofen® gel. This was statistically significant for the emulgel, gel and Pheroid™ emulgel at pH 7.4. The gel at pH 7.4 exhibited the highest release rate and flux. This was observed for the membrane and skin permeation studies. All the formulations (including Nurofen® gel) presented a correlation coefficient (r2) of 0.972 – 0.995 for membrane permeation studies, and 0.950 – 0.978 for skin permeation studies; indicating that the release of ibuprofen from each of the formulations could be described by the Higuchi model. Furthermore, all the formulations exhibited a prolonged lag time compared to Nurofen® gel which indicated that the ibuprofen was retained for a longer time by the base. This was statistically significant (p < 0.05) for the emulgel at pH 7.4, the gel and Pheroid™ emulgel at pH 5. The gel at pH 7.4 exhibited a lag time closest to that of Nurofen® gel and this difference could not be classified as statistically significant (p > 0.286). This was observed for the membrane and skin permeation studies. Nurofen® gel exhibited the highest ibuprofen concentration in the stratum corneum as well as in the epidermis followed by the gel at pH 7.4. However, results obtained for all the formulations indicated that topical as well as transdermal delivery of ibuprofen was achieved. The pH of a formulation plays an important role with respect to API permeation. Ibuprofen is reported to have a pKa value 4.4 (Dollery, 1999:I1); and by application of the Henderson-Hasselbach equation, at pH 5, 20.08% of ibuprofen will be present in its unionised form and at pH 7.4, 0.1% ibuprofen will exist in its unionised form. Since the unionised form of APIs is more lipid soluble than the ionised form, unionised forms of APIs permeate more readily across the lipid membranes (Surber & Smith, 2000:27). Therefore, it would be expected that ibuprofen formulated at pH 5 would be more permeable than formulations at pH 7.4. However, this did not correspond to the results (membrane studies) obtained in this study. It may be attributed to the solubility of ibuprofen in the different formulations. According to the pH-solubility profile of ibuprofen obtained in this study, it was more soluble at pH 7.4 than at pH 5. This was due to the fact that ibuprofen is a weak acidic compound, and for every 3 units away from the pKa-value, the solubility changes 10-fold (Mahato, 2007:14). However, with regard to the skin permeation studies, enhanced permeation was obtained with the formulations prepared at pH 5. This was in accordance with Corrigan et al., (2003:148) who stated that NSAIDs are less soluble and more permeable at low pH values, and more soluble and less permeable at high pH values. This was most probably due to the fact that unionised species, although possessing a lower aqueous solubility than the ionised species, resulted in enhanced skin permeation due to being more lipid-soluble. Finally, stability tests on the different semi-solid formulations for a period of three months at different temperature and humidity conditions were conducted to determine product stability. The formulations were stored at 25 °C/60% RH (relative humidity), 30 °C/60% RH and 40 °C/75% RH. Stability tests included: mass variation, pH, zeta potential, droplet size, visual appearance, assay, and viscosity. No significant change was observed for mass variation, pH, zeta potential and droplet size over the three months for any of the different formulations stored at the different storage conditions. In addition, no significant change in colour was observed for the gel and emulgel formulations at pH 5 and 7.4 over the three months at all the storage conditions. However, it was observed that the formulations containing Pheroid™ showed a drastic change in colour at all the storage conditions. This might have been due to oxidation of certain components present in the Pheroid™ system. Consequently, further investigation is necessary to find the cause of the discolouration and a method to prevent it. The gel formulated at pH 5 depicted the formation of crystals. This might have been due to the fact that the solubility of ibuprofen was exceeded, leading to it precipitating from the formulation. A possible contributing factor to the varying assay values obtained during the study might have been due to non-homogenous sample withdrawal. On the other hand, no significant change was observed for the emulgel and Pheroid™ emulgel formulated at pH 5 and 7.4. The emulgel and Pheroid™ emulgel formulated at pH 5 depicted relative instability (according to the International Conference on Harmonisation of Technical Requirements For Registration of Pharmaceuticals for Human Use, ICH) only at 40 °C/75% RH with a change in ibuprofen content of more than 5% (6.78 and 6.46%, respectively). The gel, emulgel and Pheroid™ emulgel at pH 7.4 exhibited the least variation in ibuprofen concentration at all of the storage conditions. This might indicate that the pH at which a semi-solid formulation is produced will have a direct influence on the stability of the product. No significant changes in viscosity (%RSD < 5) was observed for the gel and emulgel formulated at pH 7.4 and stored at 25 °C/60% RH. The remaining formulations at all of the specified storage conditions exhibited a significant change in viscosity (%RSD > 5) with a decrease in viscosity being more pronounced at the higher temperature and humidity storage conditions. A possible contributing factor to the change in viscosity over three months at the specified storage conditions might have been due to the use of Pluronic® F-127 (viscosity enhancer). This viscosity enhancer possesses a melting point of approximately 56 °C (BAST Corporation. s.a). The problem with this might have been the temperature (70 °C) at which the formulations were prepared. The higher preparation temperature might have caused the Pluronic® F-127 to degrade, thereby losing its ability to function appropriately. A balance must be maintained between optimum solubility and maximum stability (Pefile & Smith, 1997:148). Despite the lower skin permeation of the gel formulated at pH 7.4, this formulation performed the best, as it was considered stable (least variation during the 3 month stability test) and the obtained tape stripping results showed that this formulation depicted the highest ibuprofen concentrations in the stratum corneum and epidermis. Thus, topical as well as transdermal delivery were obtained.
Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

This research offers a specific strategy for the management of a global health problem associated with smoking addiction. Novel controlled release nicotine-loaded chitosan nanoparticles have been developed as a potential therapy. In vitro and in vivo evaluation of these nanoparticles indicate that they are suitable as dry powder inhaler formulations for pulmonary delivery. Results from a mouse model should translate to humans to provide a safe and effective approach to treat smoking dependence.

L’acide phosphorique et les sels de phosphates sont utilisés dans le monde entier dans la production de fertilisants, d’additifs alimentaires, mais également comme agent de gravure dans l’industrie électronique et pour diverses applications de l’industrie pharmaceutique. Selon l’application visée, un degré de pureté plus ou moins élevé peut être requis vis-à-vis d’un certain nombre d’impuretés dissoutes conjointement avec l’acide phosphorique lors de la lixiviation des roches phosphatées par l’acide sulfurique (voie humide, constituant aujourd’hui le procédé quasi exclusif de production de H₃PO₄). Il est donc nécessaire d’éliminer ces impuretés (espèces métalliques, sulfate, chlorure, etc.). A l’échelle industrielle, la purification de l’acide phosphorique est réalisée principalement par extraction liquide-liquide. L’opération consiste à extraire le plus sélectivement possible les molécules d’acide phosphorique initialement contenues dans le jus de lixiviation dans une phase organique appropriée. Cependant une telle extraction n’est pas totalement sélective et certaines impuretés sont co-extraites. Par la suite, des étapes complémentaires doivent être ajoutées, ce qui complexifie l’ensemble du procédé et le rend plus coûteux. La connaissance fine de la spéciation des impuretés gênantes présentes dans l’acide phosphorique concentré (8-14,5 mol.L⁻¹) est donc une donnée importante pour comprendre les raisons physicochimiques de leur co-extraction et, in fine, pour modifier le procédé afin de s’affranchir de cette dernière. Par exemple, les solvants actuellement utilisés ne sont pas suffisamment sélectifs vis-à-vis du titane(IV). Ce travail de thèse est donc centré sur l’étude de la spéciation du titane(IV) sur une large gamme de concentration en acide phosphorique dans le but de pouvoir identifier ultérieurement les équilibres responsables de sa co-extraction avec l’acide phosphorique. Cette thèse repose sur une approche originale combinant des méthodes d’analyses spectroscopiques et des calculs de modélisation moléculaire. Des solutions synthétiques d’acide phosphorique contenant du titane(IV) ont été caractérisées par spectroscopies UV-Visible, de Résonnance Magnétique Nucléaire (³¹P RMN) et par spectroscopie d’absorption des rayons X. Ainsi, la structure des complexes formés dans l’acide phosphorique a pu être étudiée par la comparaison des spectres UV-Visible et de calculs implémentant la théorie de la fonctionnelle de la densité dépendante du temps (TD-DFT). La nucléarité de ces complexes a également pu être évaluée en comparant les valeurs des coefficients d’autodiffusion déterminées expérimentalement par RMN ³¹P aux valeurs calculées par dynamique moléculaire pour différentes espèces de titane(IV) potentiellement présentes en solution. La coordination du titane(IV) a pu aussi être étudiée en analysant les spectres EXAFS (Extended X-Ray Absorption Fine Structure) à l’aide de simulations de dynamique moléculaire ab-initio prenant explicitement en compte la solvatation des complexes. Enfin, l’exploitation des spectres UV-Visible par un outil chimiométrique fondé sur une analyse en composants principaux a permis d’extraire des informations quantitatives sur la répartition des complexes de titane(IV) présents dans l’acide phosphorique concentré. A partir de l’ensemble de ces résultats, il a été possible de proposer pour la première fois un diagramme de spéciation du titane(IV) dans l’acide phosphorique pour une gamme de concentrations comprises entre 6 et 13 mol.L⁻¹, soulignant la présence évolutive de trois complexes de titane(IV) mono- et poly-nucléaires dont l’espèce prédominante est [Ti(OH)(H₃PO₄)₂(H₂PO₄)]²⁺
The conventional wet-process of production of phosphoric acid consists of a leaching of phosphate ores with sulfuric acid during which several impurities (metallic, sulfate, chloride are dissolved concomitantly. Phosphoric acid and phosphate salts are used in various applications such as fertilizers, food additives, electronic etching agent or pharmaceutical excipients and must therefore meet appropriate of specifications regarding their purity. As a consequence, the concentration of these impurities must be reduced by performing purification steps. At the industrial scale, the purification of phosphoric acid is performed mainly by liquid-liquid extraction. The operation consists in extracting as selectively as possible the phosphoric acid molecules initially contained in the leaching juice into an appropriate organic phase. However this process is not selective enough and some of the impurities are co-extracted. This leads to the necessity of performing additional purification steps to meet the requested specifications, which increases both the complexity of the global treatment and its cost. The knowledge of the speciation of impurities in concentrated phosphoric acid is essential to understand the physicochemical reasons for their co-extraction and, in fine, to design more selective extraction solvents. For example, the solvents presently used for the purification of H₃PO₄ are not selective enough against titanium(IV). Thus, this PhD thesis work aims at characterizing the speciation of this metal in a large range of phosphoric acid concentration, in order to identify subsequently the equilibria responsible for its co-extraction with H₃PO₄. This thesis is based on an original approach combining the use of spectroscopic and molecular modeling techniques. Synthetic solutions containing both titanium(IV) and phosphoric acid have been characterized using different spectroscopic techniques including UV-Visible, Nuclear Magnetic Resonance (³¹P NMR) and X-Ray Absorption (XAS) spectroscopies. Thus, the structure of the complexes formed in phosphoric acid has been studied by comparing UV-Visible spectra and calculations implementing time-dependent density functional theory (TD-DFT). The nuclearity of these complexes has also been estimated by comparing the values of the self-diffusion coefficients determined experimentally by ³¹P NMR with the values calculated by molecular dynamics for different species of titanium (IV) potentially present in solution. The coordination of titanium (IV) was also studied by analyzing the EXAFS (Extended X-Ray Absorption Fine Structure) spectra using ab-initio molecular dynamics simulations explicitly taking into account the solvation of the complexes.Finally, UV-Visible spectral data have been analyzed by a chemometric approach, based on a principal component analysis (PCA), allowing us to extract quantitative information about the distribution of the complex species identified in concentrated phosphoric acid. From all these results, it was possible to propose for the first time a diagram of speciation of titanium (IV) in phosphoric acid for a range of concentrations between 6 and 13 mol.L⁻¹, underlining the evolutionary presence of three mono- and poly-nuclear titanium (IV) complexes, the predominant species of which is [Ti(OH)(H₃PO₄)₂(H₂PO₄)]²⁺

AbstractData-driven machine learning (ML) models are attracting increasing interest in chemical engineering and already partly outperform traditional physical simulations. Previous work in this field has mainly focused on improving the models’ statistical performance while the thereby imparted knowledge has been taken for granted. However, also the structures learned by the model during the training are fascinating yet non-trivial to assess as they are usually high-dimensional. As such, the interpretable communication of the relationship between the learned model and domain knowledge is vital for its evaluation by applying engineers. Specifically, visual analytics enables the interactive exploration of data sets and can thus reveal structures in otherwise too large-scale or too complex data. This chapter focuses on the thermodynamic modeling of mixtures of substances using the so-called activity coefficients as exemplary measures. We present and apply two visualization techniques that enable analyzing high-dimensional learned substance descriptors compared to chemical domain knowledge. We found explanations regarding chemical classes for most of the learned descriptor structures and striking correlations with physicochemical properties.

AbstractAn exponential increase in products containing titanium dioxide nanomaterials (TiO2), in agriculture, food and feed industry, lead to increased oral exposure to these nanomaterials (NMs). Thus, the gastrointestinal tract (GIT) emerges as a possible route of exposure that may drive systemic exposure, if the intestinal barrier is surpassed. NMs have been suggested to produce adverse outcomes, such as genotoxic effects, that are associated with increased risk of cancer, leading to a concern for public health. However, to date, the differences in the physicochemical characteristics of the NMs studied and other variables in the test systems have generated contradictory results in the literature. Processes like human digestion may change the NMs characteristics, inducing unexpected toxic effects in the intestine. Using TiO2 as case-study, this chapter provides a review of the works addressing the interactions of NMs with biological systems in the context of intestinal tract and digestion processes, at cellular and molecular level. The knowledge gaps identified suggest that the incorporation of a simulated digestion process for in vitro studies has the potential to improve the model for elucidating key events elicited by these NMs, advancing the nanosafety studies towards the development of an adverse outcome pathway for intestinal effects.

Novel kinetic models considering ignition and combustion of the H2—air mixture with the account of vibrational nonequilibrium of N2, O2, H2, and OH molecules was developed. The vibrational excitation of the molecules was treated using either state-to-state or mode approximation approaches. The numerical study of the physicochemical processes in H2—air mixture behind shock wave front with Mach numbers up to M=6 were conducted and the results from state-to-state and mode approximation approaches were compared according to the predicted impacts of thermal nonequilibrium on the ignition delay time.

In order to reduce global CO2 emissions, CO2 capture based on absorption in an amine/water mixture is an established method. To develop such processes, correct physicochemical properties like densities and viscosities are important.The first objective of this work is to explore mathematical correlations for fitting viscosity data for aqueous Monoethanolamine (MEA) and Methyldiethanolamine (MDEA). A second objective is to evaluate the prediction of viscosity based on parameters independent of viscosity measurements.13 developed correlations have been evaluated by comparing the maximum deviation of fitted models to the measured property, and by determining the average absolute relative deviation (AARD%). Python 3.6, MATLAB R2020b and Excel were used as the tools for regression.The results indicated that viscosity for aqueous amines was better correlated by Eyring’s viscosity model based on NRTL (Non-Random-Two Liquid model) rather than a Redlich-Kister correlation. The achieved AARD% of aqueous MEA were 2.39 for Redlich-Kister, 1.87 for Eyring-NRTL and 1.88 for the segment-based Eyring-NRTL model. The same trend was achieved for aqueous MDEA with AARD% of 3.04, 2.23 and 1.88 for different approaches.The possibility of using data from vapor/liquid equilibrium parameters to predict viscosity in MEA/water and MDEA/water was evaluated. Using parameters in the equilibrium model NRTL from the simulation program Aspen HYSYS in a model from Karunarathne indicated that it is possible to predict viscosity reasonably well without experimental viscosity data.

In this work, based on the analysis of literature data, the main physicochemical stages that can be expected under the conditions of reaction sintering of the Ti-Al-Fe2O3system are established. Particular physical models of phase formation are analyzed under various temperature conditions, which can take place in local volumes of a heterogeneous mixture. As a reactive diffusion model example, a variant of the model for the interaction of titanium particles with an aluminum melt is presented.

Abstract Accurate prediction of the rock dissolution process is crucial for designing efficient acid stimulation treatments. At typical conditions, the dissolution of carbonates in most acids is limited by the rate of convective diffusion of reactive species to the surface of the rock. The experimental techniques used to determine the acid-diffusion coefficient are comparably well-understood by the research and engineering community. However, one important physicochemical phenomenon termed diffusion relaxation has not been studied in detail and accounted for in all the existing acid fracturing and matrix acidizing modeling software programs. The objective of this work is to address these gaps in research and optimize acid treatment designs. Diffusion relaxation occurs downstream of an inert or less reactive rock layer and results in higher mass transfer, i.e., dissolution rate of the rock located immediately downstream of an inert layer. To study the process of diffusion relaxation, 15 wt% hydrochloric acid at a temperature of 150°F was injected through a composite acid fracture model. This model was prepared by inserting 0.5 and 0.25 in.-long sandstone layers into a standard 7 in.-long fracture model made of Indiana limestone. Laser profilometry of the fracture surfaces after the experiment revealed the presence of 0.1 in.-deep channels of more etched limestone downstream of inert layers, as compared to the upstream of inert layers. The zone of an enhanced dissolution rate—termed diffusion relaxation zone—extends to a distance comparable to the length of an inert layer and appears because of the following. As soon as the acid flow encounters inert areas, the concentration of reactive species at the fracture surface starts to accumulate since there is no dissolution reaction. Right downstream the inert areas, the limestone surface contacts with the acid that has not been spent by the diffusion of reactive species. Because of that and an impact of tangential mass transfer in the diffusion boundary layer, downstream of inert areas the diffusional mass transfer significantly—often more than two times—exceeds the limiting mass transfer established upstream of the inert areas. Etched channels formed in diffusion relaxation zones contribute to the fracture conductivity, which is not considered in existing modeling software programs. Results indicate that the observed phenomenon is universal, i.e, it also occurs during dissolution of rocks with different reactivities. This research innovatively discusses the impact of physicochemical phenomena of diffusion relaxation on the dissolution of carbonate rocks, and formation of conductive flow channels. Presented results are integral for designing acid stimulation operations.

Abstract Predicting soot production in industrial systems using an LES approach represents a great challenge. Besides the complexity in modeling the multi-scale physicochemical soot processes and their interaction with turbulence, the validation of newly developed models is critical under turbulent conditions. This work illustrates the difficulties in evaluating model performances specific to soot prediction in turbulent flames by considering soot production in an aero-engine combustor. It is proven that soot production occurs only for scarce local gaseous conditions. Therefore, to obtain a statistical representation of such rare soot events, massive CPU resources would be required. For this reason, evaluating soot model performances based on parametric studies, i.e., multiple simulations, as classically done for purely gaseous flames, is CPU high-demanding for sooting flames. Then, a new strategy to investigate modeling impact on the solid phase is proposed. It is based on a unique simulation, where the set of equations describing the solid phase are duplicated. One set accounts for the reference model, while the other set is treated with the model under the scope. Assuming neglected solid phase retro-coupling on the gas phase, the soot scalars from both sets experience the same unique temporal and spatial gas phase evolution isolating the soot model effects from the uncertainties on gaseous models and numerical sensitivities. Finally, the strategy capability is proven by investigating the contribution of the soot subgrid intermittency model to the prediction of soot production in the DLR burner.

Biochar is produced by heating biomass in the total or partial absence of oxygen. This report addresses the long-term persistence of biochar in soil and how this can be managed in climate calculations and reporting. The report consists of this summary and four chapters, which can be read independently. Different terms have been used to describe the durability of biochar carbon storage, but also the physical presence of biochar in soils, e.g. persistence, permanence, recalcitrance, residence times, stability. Today, the term “durability of carbon storage” is preferred in policy contexts, but various academic disciplines such as soil science have other established terms like “persistence”. Here, both durability and persistence are used, rather interchangeably. It is important to be aware of differences in meaning that exist between disciplines. The purpose of this report is to present the state of knowledge regarding the proportion of carbon in biochar that remains in the soil over time and provide recommendations for calculating this. There is a need to calculate the persistence of biochar in soil for national climate reporting, corporate climate reporting, carbon credit trading, and life cycle assessments for various purposes. On the persistence of biochar The amount of biochar remaining after a certain time depends on the properties of the biochar and the environment in which it is located. Nearly all research on biochar persistence has focused on its application in agricultural soils. The main reason for the high durability of biochar carbon storage is the formation of fused aromatic stable structures during biomass pyrolysis. A high degree of fused aromatic structures makes biochar much less prone to microbial decomposition than fresh biomass. Different biochars have different properties, and this influences how long they persist in the soil. To achieve biochar with properties that provide higher persistence, it should be produced at higher temperatures for a sufficient duration. Measuring and calculating biochar persistence Established quantification methods of 100-year biochar persistence (e.g. referenced in IPCC inventory guidelines and used in voluntary carbon markets, to date) extrapolate short-term soil decomposition processes, and do not fully consider the processes that may explain millennial persistence. Calculations regarding biochar persistence have traditionally used a time span of 100 years to describe the amount of remaining carbon after a certain time. The use of specifically 100 years lacks a well founded scientific reason, but has been regarded as “far enough” into the future from a climate perspective and close enough for modelling to be meaningful. An active area of research relevant for the understanding biochar carbon storage durability is the development of advanced analytical characterisation methods of biochar that will enable measurement of the physicochemical heterogeneity in carbon structures present in biochar. Another area of continued research is biochar incubation, with a focus on field conditions, to elucidate both differences from laboratory conditions, and how transport processes affect biochar in the field. Recommendation and conclusion In the project, available research data has been aggregated into a functional model that calculates how much of the carbon in biochar remains after a given number of years. The model is based on the H/C ratio of the biochar placed in the soil and the annual average temperature at the location. The model is made freely accessible to provide biochar market actors with the best available knowledge for estimating the durability of biochar carbon. Existing research results provide a sufficient foundation for estimation of the amount of biochar expected to remain over time. Future research results are expected to lead to increased knowledge regarding the decomposition properties of biochar, in particular biochars with a very low H/C ratio. Therefore, this recommendation will be revised by the end of the project in 2025.

The project sought to understand factors and mechanisms involved in the hardening of potato tubers. This syndrome inhibits heat softening due to intercellular adhesion (ICA) strengthening, compromising the marketing of industrially processed potatoes, particularly fresh peeled-cut or frozen tubers. However, ICA strengthening occurs under conditions which are inconsistent with the current ideas that relate it to Ca-pectate following pectin methyl esterase (PME) activity or to formation of rhamnogalacturonan (RG)-II-borate. First, it was necessary to induce strengthening of the middle lamellar complex (MLX) and the ICA as a stress response in some plant parenchyma. As normally this syndrome does not occur uniformly enough to study it, we devised an efficient model in which ICA-strengthening is induced consistently under simulated stress by short-chain, linear, mono-carboxylic acid molecules (OAM), at 65 oC [appendix 1 (Shomer&Kaaber, 2006)]. This rapid strengthening was insufficient for allowing the involved agents assembly to be identifiable; but it enabled us to develop an efficient in vitro system on potato tuber parenchyma slices at 25 ºC for 7 days, whereas unified stress was reliably simulated by OAMs in all the tissue cells. Such consistent ICA-strengthening in vitro was found to be induced according to the unique physicochemical features of each OAM as related to its lipophilicity (Ko/w), pKa, protonated proportion, and carbon chain length by the following parameters: OAM dissociation constant (Kdiss), adsorption affinity constant (KA), number of adsorbed OAMs required for ICA response (cooperativity factor) and the water-induced ICA (ICAwater). Notably, ICA-strengthening is accompanied by cell sap leakage, reflecting cell membrane rupture. In vitro, stress simulation by OAMs at pH<pKa facilitated the consistent assembly of ICAstrengthening agents, which we were able to characterize for the first time at the molecular level within purified insoluble cell wall of ICA-strengthened tissue. (a) With solid-state NMR, we established the chemical structure and covalent binding to cell walls of suberin-like agents associated exclusively with ICA strengthening [appendix 3 (Yu et al., 2006)]; (b) Using proteomics, 8 isoforms of cell wall-bound patatin (a soluble vacuolar 42-kDa protein) were identified exclusively in ICA-strengthened tissue; (c) With light/electron microscopy, ultrastructural characterization, histochemistry and immunolabeling, we co-localized patatin and pectin in the primary cell wall and prominently in the MLX; (d) determination of cell wall composition (pectin, neutral sugars, Ca-pectate) yielded similar results in both controls and ICA-strengthened tissue, implicating factors other than PME activity, Ca2+ or borate ions; (e) X-ray powder diffraction experiments revealed that the cellulose crystallinity in the cell wall is masked by pectin and neutral sugars (mainly galactan), whereas heat or enzymatic pectin degradation exposed the crystalline cellulose structure. Thus, we found that exclusively in ICA-strengthened tissue, heat-resistant pectin is evident in the presence of patatin and suberinlike agents, where the cellulose crystallinity was more hidden than in fresh control tissue. Conclusions: Stress response ICA-strengthening is simulated consistently by OAMs at pH< pKa, although PME and formation of Ca-pectate and RG-II-borate are inhibited. By contrast, at pH>pKa and particularly at pH 7, ICA-strengthening is mostly inhibited, although PME activity and formation of Ca-pectate or RG-II-borate are known to be facilitated. We found that upon stress, vacuolar patatin is released with cell sap leakage, allowing the patatin to associate with the pectin in both the primary cell wall and the MLX. The stress response also includes formation of covalently bound suberin-like polyesters within the insoluble cell wall. The experiments validated the hypotheses, thus led to a novel picture of the structural and molecular alterations responsible for the textural behavior of potato tuber. These findings represent a breakthrough towards understanding of the hardening syndrome, laying the groundwork for potato-handling strategies that assure textural quality of industrially processed particularly in fresh peeled cut tubers, ready-to-prepare and frozen preserved products.