Propriedades e comportamento de soluções de hidrocarbonetos pesados a baixas temperaturas: medição e modelação

Fruto da constante evolução da ciência e da tecnologia, referências ao uso de novos fluídos surgem a um ritmo cada vez maior. Novos refrigerantes, mais “amigos” do ambiente, líquidos iónicos, uma nova classe de solventes ou perfluorocarbonetos, moléculas capazes de dissolver suficiente oxigénio para poderem ser utilizadas como substitutas do sangue ou como fonte de oxigénio em processos biotecnológicos ou ainda como surfactantes em processos de extracção supercrítica com dióxido de carbono, são apenas alguns dos novos exemplos. Para o design correcto de produtos e processos envolvendo estes novos fluídos, o conhecimento de algumas das suas propriedades termofísicas é fundamental. Embora a medição experimental seja o procedimento mais rigoroso para a determinação de qualquer propriedade termofísica, muitas das vezes, estas medições são morosas e caras. As gamas de temperatura, pressão e composição de interesse podem ainda ser tais que tornam as medições experimentais inexequíveis sendo a solução mais conveniente a utilização de um modelo teórico, empírico ou misto que devolve o valor da propriedade termofísica nas condições desejadas com uma razoável exactidão. O contributo desta dissertação de doutoramento é maioritariamente para o estudo de moléculas lineares de diferentes tamanhos de cadeia, com um especial ênfase para misturas assimétricas. A família dos n-alcanos por apresentar um imenso interesse industrial a nível da indústria petrolífera e petroquímica, quer porque as suas propriedades permitem a sua utilização como materiais termoactivos em isolamento ou armazenamento de energia, quer ainda por ser uma família modelo para tantas outras moléculas, como surfactantes, ácidos gordos ou polímeros, foi seleccionada para esse efeito. Várias medições foram realizadas em sistemas cuja escassez ou inexistência de dados experimentais foi verificada. Tensões superficiais, tensões interfaciais, densidades e viscosidades da fase líquida foram determinadas para um conjunto significativo de fluídos em gamas alargadas de temperatura e composição, tendo sido dada especial atenção a sistemas assimétricos de n-alcanos e a algumas fracções de petróleo, representativas de sistemas reais. Diferentes metodologias foram adoptadas para a modelação dos resultados obtidos, com o cuidado de avaliar alguns dos modelos termodinâmicos que constituem o estado-da-arte, tendo sido demonstrado que um novo modelo baseado no Princípio dos Estados Correspondentes introduz melhorias consideráveis na modelação quando comparado com modelos convencionais.As a result of the continuous scientific and technological developments, several new fluids of interest are showing up every day. New refrigerants, more environmentally friendly, ionic liquids, a new class of solvents or perfluoroalkanes, molecules able to dissolve enough oxygen in order to be used as blood substitutes or oxygen carrier agents in biotechnological processes or as surfactants in supercritical carbon dioxide extraction, are a few examples. For the correct product and process design of these new fluids, knowledge of some thermophysical properties are required. Although the experimental measurement is the most rigorous procedure for evaluating any thermophysical property, frequently these are expensive and time-consuming. The temperature, pressure and composition ranges of interest may also be so broad that the measurements may be unfeasible, with a common solution being the use of a theoretical, empirical or semi-empirical model that returns the thermophysical property at the desired conditions with a considerable accuracy. This thesis contributes to the study of various thermophysical properties of nonpolar molecules of different chain lengths, with a special emphasis on asymmetric mixtures. The n-alkane family was chosen for that purpose since it has a vast industrial interest, starting from the petrochemical industry to termoactive phase change materials, for energy storage and release. It can also be regarded as a reference family for studying other molecules such as surfactants, fatty acids or polymers. A number of experimental measurements were performed in systems were data deficiency was found. Properties such as vapor-liquid and liquidliquid interfacial tensions and liquid phase densities and viscosities were measured for a significant number of fluids in broad ranges of temperature and composition. A special emphasis was put on asymmetric n-alkane mixtures and some petroleum fractions, representative of real systems. Several methodologies were adopted for modeling the obtained results, and for that purpose some state-of-the-art thermodynamic models were evaluated. As will be demonstrated an improved Corresponding States model enhanced considerably model accuracy

Pure solvent solubility of some pharmaceutical molecules

During the search for novel or improved therapies, new drugs are proposed. Solubility of drug-candidates is important both for drug production and its therapeutic use. Many separation processes in the pharmaceutical industry are based on the solubilities in different solvents. Solvation plays an important role in the organism in each stage of drug transport and delivery. Properties like lipophilicity, hydrophilicity, the ability to establish hydrogen bonds and other interactions of the molecules with the surrounding media play an important role in the solvation process. Although some predictive thermodynamic tools can be used to determine drug solubility, the availability of experimental data is still fundamental for an appropriate model development and evaluation. In this work, solubilities of some drugs, such as paracetamol, budesonide, furosemide and allopurinol, were measured in the temperature range between 25 °C and 42 °C, in pure solvents (water, ethanol, acetone, n-hexane, ethyl acetate and carbon tetrachloride). The Non-random Two-Liquid Segment Activity Coefficient (NRTL-SAC) equation (Chen and Song 2004), one of the most successful models for the representation of drug solubility, was used to model the data. The obtained agreement is very satisfactory (root mean square deviation of 0.051)

Comparing approaches for drug-like molecules solubility calculations

Solubility has been recognized as one of the most important properties for designing separation and purification processes of complex molecules, such as active pharmaceutical ingredients. Experimental solubility data are usually needed for performing such design operations. However, frequently data are unavailable due to reduced amounts of sample, time limitations, or inherent complexities with experimental measurements. In such cases, thermodynamic models can be the more theoretically sound tools to generate solubility estimates. In this work, the group-contribution method UNIFAC, and the NRTL-SAC activity coefficient model, are used to correlate and predict solubility in pure and mixed solvents of a set of representative drug-like molecules such as benzoic, salicylic and acetylsalicylic acids, ibuprofen, hydroquinone, estriol, estradiol and resveratrol. Generally, UNIFAC and NRTL-SAC models are able to represent the data, with NRTL-SAC being better for pure solvent solubilities. Solubility dependence with temperature and solvent composition were also taken into account. Whenever possible, the reference solvent approach was also applied, and the results were generally improved with any of the models. The average percent absolute deviations obtained for the representation of solubility data in pure solvents are very satisfactory, but for mixed solvents higher deviations are possible to find

Solid-liquid equilibria of some natural phenolic compounds: experimental and modelling

Phenolic compounds are typically found in plants, usually as esters or glycosides [1]. Apart from being starting materials for many chemical synthesis, there is also huge evidence that some phenolic compounds have beneficial effects on human health. In this work, the aqueous solubilities of some phenolic compounds such as the hydroxybenzoic acids gallic, salicylic, protocatechuic and syringic acids, and the phenilpropenoic acids caffeic, cinnamic, ferulic and coumaric acids are addressed. Measurements were performed, as a function of temperature, between 288 K and 323 K, at atmospheric pressure, using constant-temperature jacketed equilibrium glass cells. Approaches for modelling the measured data were evaluated, including the modified UNIQUAC model [2] and the CPA equation of state [3]

Aqueous solubility of some natural phenolic compounds

In this work, the aqueous solubilities of two hydroxybenzoic acids (gallic and salicylic acid) and three phenylpropenoic acids (trans-cinnamic, ferulic, and caffeic acids) are addressed. Measurements were performed, as a function of temperature, between 288.15 and 323.15 K, using the shake-flask method for generating the saturated aqueous solutions, followed by compositional analysis by spectrophotometric and gravimetric methods. The pH values of the saturated aqueous solutions were measured by potentiometry. Additional thermodynamic properties, which are fundamental for a better understanding of the solubilization process, as well as necessary for the modeling studies, such as melting temperatures and fusion enthalpies were determined by differential scanning calorimetry (DSC). Apparent acid dissociation constants (Ka) were obtained by potentiometry titration. The measured data were modeled with the cubic-plus-association (CPA) equation of state (EoS). This EoS is applied, for the first time, for multifunctional associating molecules, and the results indicate that it can adequately be used to represent the measured and other literature data with satisfactory accuracy

Solid-liquid equilibria of some pharmaceutical compounds

Solubility is an important property which affects the release, transport and absorption of drugs. Solubility data involving new drug molecules and their precursors are frequently unavailable hampering drug formulation. Although some thermodynamic models can be used, the existence of some experimental data is still fundamental for an appropriate model development and evaluation. In this work, solubilities of some drugs, such as paracetamol, budesonide, allopurinol and flurosemide were measured as a function of the temperature in several solvents, namely water, ethanol and acetone. Solubilities were determined by the analytical shake-flask method, using constant temperature jacketed glass cells for generating the saturated solutions, followed by composition analysis by HPLC. As the analytical shake-flask method is an expensive and time consuming procedure, an alternative method to measure solubility using DSC was also studied [1] with the advantage of being faster and consuming smaller amounts of sample. Melting data of the, pure drugs were also obtained by DSC. The NRTL-SAC model [2j was used to represent the measured data. This model provides a simple and practical thermodynamic framework for phase equilibria of drug systems. A comparison between experimental and model results showed that NRTL-SAC is an appropriate tool to represent the solubility of these complex molecules

Solubilities of some pharmaceutical compounds in pure solvents

Solubility is an important property which affects the release, transport and absorption of drugs. It also affects drug’s efficacy, its future development and formulation effort [1]. Therefore, its measurements must be carried out in an initial step of the drug development. Solubility data involving new drug molecules and their precursors are frequently unavailable, which hampers the development and evaluation of predictive methodologies. In this work solubilities of some drugs, such as paracetamol, budesonide, and furosemide, were measured, as a function of temperature, in several solvents, such as water, ethanol and acetone. The shake-flask method was used to obtain the saturated solutions and the compositions were determined by HPLC analysis. In spite of being the most reliable and standard technique to measure solubilities, it is very time consuming and is limited when samples are expensive and available in low amounts. An alternative methodology using differential scanning calorimetry [2] was used, with the advantage of being faster and consuming smaller quantities of sample

Temperature and solvent effects in the solubility of some drugs: experimental and modeling

New drugs are always appearing during the development of new therapies or the improvement of existing ones. The effects of these drugs in the organism are dependent on the techniques used by the pharmaceutical industry to make them more soluble [1]. Solubility data involving new drug candidates are frequently not available in the open literature and, although predictive thermodynamic models can be used, the availability of experimental data is still fundamental for an appropriate model development and evaluation. One of the most recent and successful models is the Nonrandom Two Liquid Segment Activity Coefficient (NRTL-SAC) model [2-5], which gives reasonable results in the prediction of drug solubilities and has been widely applied to correlate and predict phase equilibria of highly nonideal systems, both in pure and mixed systems, both at academic and industrial level

Solubility of phenolic compounds in water, organic and supercritical solvents

Phenolic compounds represent a class of important chemicals with both biological and industrial importance. Their production, either by chemical synthesis or extraction from different biological media requires the adequate knowledge of phase equilibria. Particularly, the solubility in aqueous systems organic and supercritical solvents are fundamental for a better design of separation and purification processes