[pt] A injeção química, principalmente de surfactantes, é um dos métodos mais utilizados na recuperação melhorada de petróleo. Uma das principais limitações deste método é a perda devido à partição do surfactante para o óleo presente no reservatório. O estudo do equilíbrio de partição água-óleo de formulações de surfactantes torna-se relevante devido a perda existente nos reservatórios, afetando a inviabilidade econômica e ambiental da aplicação. O objetivo deste trabalho foi determinar o coeficiente de partição de surfactantes entre as fases água e óleo através de diferentes métodos analíticos. Foram estudados os surfactantes dodecilbenzeno sulfonato de sódio (SDBS, de tipo aniônico) e o polioxietileno (9- 10) p-teroctil fenol (Triton X-100, de tipo não iônico), e foi utilizado hexadecano como óleo modelo. Com o objetivo de identificar qual seria o melhor procedimento para a quantificação dos surfactantes na fase aquosa e, por conseguinte determinar o coeficiente de partição, foram desenvolvidas três metodologias de quantificação utilizando diferentes técnicas (medidas de tensão interfacial, medidas de absorbância UV-Vis e HPLC com detecção UV). Testes iniciais de solubilidade mostraram que o SDBS é praticamente insolúvel em presença de sal, pelo qual só foram realizados experimentos com este surfactante, em ausência de sal. Para ambos os surfactantes os resultados mostraram uma baixa partição para a fase oleosa, tanto na ausência quanto na presença de sal. Em algumas soluções foi identificada a formação de emulsões devido à concentração do surfactante e a proporção água/óleo utilizada, o qual interferiu com o método espectrofotométrico. Adicionalmente, se estabeleceu uma comparação entre os resultados obtidos pelas metodologias desenvolvidas que permitiram identificar que o melhor dos métodos estudados para a avaliação do equilíbrio de partição foi a cromatografia líquida de alta eficiência (HPLC). A partir destes resultados, pode-se concluir que os surfactantes estudados possuem um baixo valor de coeficiente de partição para a fase óleo, tornando o método de injeção química favorável para a recuperação avançada de petróleo. / [en] Chemical injection, mainly of surfactants, is one of the most used methods for improved oil recovery. One of the main limitations of this method is the loss due to partitioning of the surfactant into the oil present in the reservoir. The study of the water-oil partition balance of surfactant formulations becomes relevant due to the existing loss in the reservoirs, affecting the economic and environmental unfeasibility of the application. The objective of this work was to determine the partition coefficient of surfactants between the water and oil phases using different analytical methods. The surfactants sodium dodecylbenzene sulfonate (SDBS, anionic type) and polyoxyethylene (9-10) p-teroctyl phenol (Triton X-100, nonionic type) were studied, and hexadecane was used as model oil. In order to identify which would be the best procedure for the quantification of surfactants in the aqueous phase and, therefore, to determine the partition coefficient, three quantification methodologies were developed using different techniques (interfacial tension measurements, UV-Vis absorbance measurements, and HPLC with UV detection). Initial solubility tests showed that SDBS is practically insoluble in the presence of salt, so experiments with this surfactant were only carried out in the absence of salt. For both surfactants, the results showed a low partition for the oil phase, both in the absence and in the presence of salt. In some solutions, the formation of emulsions was identified due to the surfactant concentration and the water/oil ratio used, which interfered with the spectrophotometric method. In addition, a comparison was established between the results obtained by the developed methodologies, which allowed to identify that the best method for the evaluation of the partition equilibrium was the high performance liquid chromatography (HPLC). From these results, it can be concluded that the studied surfactants have a low partition coefficient for the oil phase, making the chemical injection method favorable for advanced oil recovery.

In the fall of 2006, soils from three small valleys in the Laxemar/Oskarshamn area were sampled. A total of eight composite samples were characterized for a number of soil parameters that are important for geochemical sorption and were later also used in batch sorption experiments. Solid/liquid partition coefficients (Kd values) were then determined for seven radionuclides in each of the eight samples. To contribute to the interpretation of the sorption results together with the soil characterizations, this study aims to describe the sorption behavior of the radionuclides caesium, nickel and uranium and also discern which parameters that could provide a basis for estimating the strength of sorption of radionuclides in general. The methodology included quantitative methodologies such as compilation of chemical equilibrium diagrams by the software Hydra/Medusa and correlation analyses using the statistical software SPSS statistics. Based on the speciation diagrams of each radionuclide and identified important linear and non-linear relationships of the Kd values with a number of soil parameters, the following soil- and soil solution properties were found to have controlled the sorption of Cs, Ni and U, respectively, in the Laxemar soils. Cs: the specific surface area of the soil coupled to the clay content. Ni: the cation exchange capacity, alkaline solution pH, soil organic matter and dissolved organic matter. U: the cation exchange capacity, soil organic matter, dissolved organic matter, dissolved carbonate and alkaline solution pH. The soil that showed the strongest sorption varied between the nuclides, which can be related to the individual sorption behavior of caesium, nickel and uranium, as well as the different physicochemical properties of the soils. The parameters that should be prioritized in characterizations of soil samples are identified to be: solution pH, the cation exchange capacity, the specific surface area of the soil, soil organic matter and soil texture (clay content). / För att kunna fatta beslut relaterade till hypotetisk framtida kontaminering från slutförvar av radioaktivt avfall är det direkt avgörande att förstå mobiliteten av radioaktiva element i miljön. Sorption är en av de viktigaste kemiska mekanismerna som kan minska spridningen av radionuklider i vatten/jord/bergssystem, där nukliderna fördelar sig mellan vätskefasen och ytor på fasta partiklar i dessa system. Fördelningskoefficienter (Kd värden) används generellt som ett kvantitativt mått på sorptionen, där ett högt Kd värde innebär att en större andel av ämnet i fråga är bundet till den fasta fasen. Under hösten 2006 togs jordprover från tre dalgångar i Laxemar/Oskarshamn. Totalt åtta jordprover karakteriserades för ett antal jordparametrar som är viktiga för geokemisk sorption och användes senare i batchförsök tillsammans med ett naturligt grundvatten. Fördelningskoefficienter (Kd värden) bestämdes för sju radionuklider (Cs, Eu, I, Ni, Np, Sr and U) för vart och ett av de åtta jordproverna. För att bidra till tolkningen av sorptionsresultaten tillsammans med jordprovernas egenskaper syftar denna studie till att beskriva sorptionsbeteendet hos radionukliderna caesium, nickel och uran samt urskilja vilka parametrar som kan fungera som grund för att uppskatta sorptionsstyrkan av radionuklider i allmänhet. För att uppnå detta syfte så har studien följande mål. Identifiera de jord- och marklösningsegenskaper som kontrollerar sorptionen av Cs, Ni respektive U i de åtta Laxemar proverna. Bestämma vilket Laxemar-jordprov som starkast sorberar de tre radionukliderna. Identifiera de jordparametrar som bör prioriteras vid jordkarakteriseringar, baserat på deras sorptionsinflytande, för att kunna uppskatta Kd värden endast med begränsad information om ett jordsystem. Metoden innefattade kvantitativa metoder såsom sammanställning av kemiska jämviktsdiagram med programvaran Hydra/Medusa och korrelationsanalyser med hjälp av statistikprogramvaran SPSS statistics. De kemiska jämviktsdiagrammen bidrog till att beskriva specieringen av respektive nuklid som en funktion av pH och korrelationsanalyserna bidrog till att identifiera linjära samband mellan par av variabler, tex mellan Kd och jordparametrar. Baserat på specieringsdiagrammen för varje radionuklid och identifierade viktiga linjära och icke-linjära förhållanden mellan Kd-värdena och ett antal jordparametrar har följande egenskaper hos jordarna och marklösningen visat sig huvudsakligen kontrollera sorptionen av Cs, Ni respektive U i de åtta Laxemar jordarna: För caesium gäller jordens specifika ytarea kopplad till lerinnehållet, medan för nickel är det katjonbytarkapaciteten, organiskt material, alkaliska pH-värden samt löst organiskt material. Sorptionen av uran befanns kontrolleras av katjonbytarkapaciteten, organiskt material, löst organiskt material, alkaliska pH-värden samt lösta karbonater. Den jord som visade starkast sorption varierar mellan de tre nukliderna, vilket kan relateras till nuklidernas individuella sorptionsbeteende i jord samt jordarnas olika fysikaliska och kemiska egenskaper. Parametrarna som bör prioriteras vid karaktärisering av jordprov identifierades vara: pH, katjonbytarkapaciteten, jordens specifika ytarea, mängden organiskt material samt jordtexturen (lerinnehåll).

Understanding the different igneous processes that magmas undergo is important for a variety of reasons including potential hazards associated with volcanoes in populated regions, magmatic hydrothermal ore deposition, and tectonic processes. One method of obtaining geochemical data that can help constrain petrogenetic processes is through the study of melt and fluid inclusions. The research presented here examines melt inclusions through experimental, analytical and field studies to better understand igneous petrogenesis. One potential problem associated with melt inclusions is water-loss during laboratory heating. A Raman spectroscopic technique was developed to determine water contents of silicate glasses, and this technique was applied to monitor water loss from natural melt inclusions that were heated for varying lengths of time. The results suggest that water loss is insignificant when heated for less than 12 hours but significant water loss can occur with longer duration heating. The distribution of trace elements between silicate melts and phenocrysts growing from that melt can constrain igneous processes such as fractional crystallization, assimilation, and partial melting. Partition coefficients were determined for syngenetic clinopyroxene, orthopyroxene, and plagioclase in equilibrium with a dacitic melt using the Melt Inclusion-Mineral (MIM) technique. Melt inclusion chemistry is the same regardless of mineral host phase, suggesting that the melt inclusions have not been subjected to re-equilibration processes or boundary layer development. Partition coefficients from this study are similar but typically lower than published values. Three closely-spaced monogenetic eruptive units from the active Campi Flegrei volcanic system (Italy) with similar eruptive styles were examined to better understand the evolution of the magmatic system. Results suggest fractional crystallization as the dominant process taking place over time but that magma mixing was significant for one of the eruptions. Trace element geochemical data suggest a mixed magma source of within-plate and volcanic arc components, and still retain a T-MORB signature from the subducting slab. / Ph. D.

Yes / The extraction of bioactive compounds, produced by plant cell cultures, directly from their culture medium, which contains other by-products, is a great challenge. Resveratrol extraction from its grapevine cell cultures is considered here as an example to improve the extraction processes from plant cell cultures using solubility parameters. Successive liquid-liquid extraction (LLE) processes were exploited to extract resveratrol from the culture medium with an extraction ratio approaching 100%, high selectivity and minimum amounts of solvents. The calculations of partition coefficients as a function of solubility parameters demonstrated that benzyl benzoate is the most suitable intermediate solvent to extract resveratrol from its aqueous medium. The calculations also illustrated the high ability of methanol and ethanol to extract resveratrol from benzyl benzoate. The physicochemical properties of benzyl benzoate and processing conditions were exploited to separate it from aqueous media and organic solvents. The agitation method, component ratios and extraction time were studied to maximize the extraction yield. Under the best studied conditions, the recovery of resveratrol from different culture media approached ∼100% with a selectivity of ∼92%. Ultimately, the improved extraction processes of resveratrol are markedly efficient, selective, rapid and economical. / Mohammad Amin Mohammad gratefully acknowledges CARA (The Council for At-Risk Academics, Stephen Wordsworth and Ryan Mundy) for providing the financial support for an academic fellowship.

Heightened concerns for cleaner air and increasingly more stringent regulations on sulphur content in transportation fuels will make desulphurization more and more important. The sulphur problem is becoming more serious in general, particularly for diesel fuels as the regulated sulphur content is getting an order of magnitude lower, while the sulphur contents of crude oils are becoming higher. This thesis aimed to develop a desulphurisation process (based on oxidation followed by extraction) with high efficiency, selectivity and minimum energy consumption leading to minimum environmental impact via laboratory batch experiments, mathematical modelling and optimisation. Deep desulphurization of model sulphur compounds (di-n-butyl sulphide, dimethyl sulfoxide and dibenzothiophene) and heavy gas oils (HGO) derived from Libyan crude oil were conducted. A series of batch experiments were carried out using a small reactor operating at various temperatures (40-100 °C) with hydrogen peroxide (H2O2) as oxidant and formic acid (HCOOH) as catalyst. Kinetic models for the oxidation process are then developed based on 'total sulphur approach'. Extraction of unoxidised and oxidised gas oils was also investigated using methanol, dimethylformamide (DMF) and N-methyl pyrolidone (NMP) as solvents. For each solvent, the 'measures' such as: the partition coefficient (KP), effectiveness factor (Kf) and extractor factor (Ef) are used to select the best/effective solvent and to find the effective heavy gas oil/solvent ratios. A CSTR model is then developed for the process for evaluating viability of the large scale operation. It is noted that while the energy consumption and recovery issues could be ignored for batch experiments these could not be ignored for large scale operation. Large amount of heating is necessary even to carry out the reaction at 30-40 °C, the recovery of which is very important for maximising the profitability of operation and also to minimise environmental impact by reducing net CO2 release. Here the heat integration of the oxidation process is considered to recover most of the external energy input. However, this leads to putting a number of heat exchangers in the oxidation process requiring capital investment. Optimisation problem is formulated using gPROMS modelling tool to optimise some of the design and operating parameters (such as reaction temperature, residence time and splitter ratio) of integrated process while minimising an objective function which is a coupled function of capital and operating costs involving design and operating parameters. Two cases are studied: where (i) HGO and catalyst are fed as one feed stream and (ii) HGO and catalyst are treated as two feed streams. A liquid-liquid extraction model is then developed for the extraction of sulphur compounds from the oxidised heavy gas oil. With the experimentally determined KP multi stage liquid-liquid extraction process is modelled using gPROMS software and the process is simulated for three different solvents at different oil/solvent ratios to select the best solvent, and to obtain the best heavy gas oil to solvent ratio and number of extraction stages to reduce the sulphur content to less than 10 ppm. Finally, an integrated oxidation and extraction steps of ODS process is developed based on the batch experiments and modelling. The recovery of oxidant, catalyst and solvent are considered and preliminary economic analysis for the integrated ODS process is presented.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with high levels of tumour necrosis factor-alpha (TNF-a) in synovial fluid and synovial tissue (Saxne et al., 1989). Thalidomide is a proven inhibitor of the biological synthesis of TNF-a (Sampaio et al., 1991) and is believed to rely on this action for its suppression of the wasting of tissue which accompanies RA. Oral administration of thalidomide has proven to be effective in RA, but unacceptable side effects are easily provoked (Gutierrez-Rodriguez, 1984). Administration of thalidomide via the dermal route can down-regulate TNF-a production in and around the affected joint, and this without raising the systemic blood level to a problematical level. Based on thalidomide's physicochemical properties, it is unlikely that it can be delivered percutaneously at a dose required for RA. Therefore, we have embraced the idea of using N-alkyl analogues of thalidomide. The most important feature that an analogue of this compound might contribute is decreased crystallinity and increased lipophilicity. Ordinarily both these parameters should favour percutaneous delivery. The current study was primarily aimed at exploring the feasibility of percutaneous delivery of thalidomide and subsequently, three of its odd chain IV-alkyl analogues (methyl, propyl and pentyl) via physicochemical characterization and assessment of their innate abilities to diffuse through skin as an initial step towards developing a topical dosage form for the best compound. The biological activities, more specifically their potential to inhibit the production of TNF-a was determined for thalidomide and its N-alkyl analogues. In order to achieve the objectives, the study was undertaken by synthesizing and determining the physicochemical parameters of thalidomide and its N-alkyl analogues. A high level of crystallinity is expressed in the form of a high melting point and heat of fusion. This limits solubility itself, and thus also sets a limit on mass transfer across the skin. Generally, the greater a drug's innate tendency to dissolve, the more likely it is that the drug can be delivered at an appropriate rate across the skin (Ostrenga et al., 1971). Therefore, the melting points and heats of fusion were determined by differential scanning calorimetry. Aqueous solubility and the partition coefficient (relative solubility) are major determinants of a drug's dissolution, distribution and availability. N-octanollwater partition coefficients were determined at pH 6.4. Solubilities in water, a series of n-alcohols and mixed solvents were obtained, as well as the solubility parameters of the compounds in study. Secondly, in vitro permeation studies were performed from these solvents and vehicles using vertical Franz diffusion cells with human epidermal membranes. Thirdly, tumour necrosis factor-alpha (TNF-a) inhibition activities were assessed for thalidomide and its N-alkyl analogues. By adding a methyl group to the thalidomide structure, the melting point drops by over 100°C and, in this particular instance upon increasing the alkyl chain length to five -CH2- units the melting points decrease linearly. Heats of fusion decreased dramatically upon thalidomide's alkylation as well. Methylation of the thalidomide molecule enhanced the aqueous solubility 6-fold, but as the alkyl chain length is further extended from methyl to pentyl, the aqueous solubility decreased exponentially. The destabilization of the crystalline structure with increasing alkyl chain length led to an increase in lipophilicity and consequently an increase in solubility in nonpolar media. Log partition coefficients increased linearly with increasing alkyl chain length. Solubilities in a series of n-alcohols, methanol through dodecanol, were found to be in the order of pentyl > propyl > methyl > thalidomide. The N-alkyl analogues have more favourable physicochemical properties than thalidomide to be delivered percutaneously. The in vitro skin permeation data proved that the analogues can be delivered far easier than thalidomide itself. N-methyl thalidomide showed the highest steady-state flux through human skin from water, n-alcohols and combination vehicles. Thalidomide and its N-alkyl analogues were all active as TNF-a inhibitors. Finally, active as a TNF-a inhibitor, N-methyl thalidomide is the most promising candidate to be delivered percutaneously for treatment of rheumatoid arthritis, of those studied. / Thesis (PhD (Pharmaceutics))--PU for CHE, 1999.

Mass transfer intervening during the process of immersion influences the final composition of the product. These transfers primarily depend on the size of the immersed products, as well as temperature, the concentration and the nature of the solution of immersion. The main objective of this work is to study the mass transfer phenomena (water loss and solid gain) in solid/liquid system constituted of vegetable product (eggplant) immerged in salt solution. We determined the kinetic studies of eggplant in different salts solutions with two concentrations (saturation and 20%) at 3°C. The physicochemical properties of solution and salt such as molar concentration, molecular weight and ionic type affected the mechanism of water loss and solid gain. Knowledge about interaction ions/vegetable pectin is important for new product formulation. Determination of partition coefficient of ion in equilibrium system showed that the main physicochemical properties of ions and solution are ionic radius, electronegativity, ionic force and molar concentration. Mathematical predictive model was developed to predict the partition coefficient of ions in food/ solution system. Molecular dynamics simulations using a dynamic force field have been carried out to investigate the absorption of ions (K+, Na+, Ca2+, Mg2+, Cl-) in pectin/water/ion/aqueous solution system. Four systems were used. The results showed that the ionic type (cation and anion) influence the type and number of interactions between pectin-ion and water-ion and then offered an explicit description transfer phenomena and distribution of ions in the system solid/liquid / Les transferts de matière intervenant au cours du procédé d’immersion dépendent essentiellement de la taille des produits immergés, la température, la concentration et la nature de la solution d'immersion. L’objectif principal de ce travail porte sur l’étude des transferts dans un système solide/liquide constitué d’un produit végétal (aubergine) et d’une solution saline. Afin de parvenir à une bonne maîtrise de ces paramètres, les études cinétiques ont été conduites à 3°C sur des aubergines immergées dans des solutions salines avec deux concentrations. Les propriétés des solutions et des sels telles que la concentration molaire, la masse molaire et surtout la nature ionique influencent le mécanisme de perte et de gain. Les connaissances sur les interactions ions/pectines végétaux sont importants pour la formulation de nouveaux produits La détermination du coefficient de partage des ions à l’équilibre dans le système aubergine/solution ont montré que les principales propriétés des ions et des solutions influençant le coefficient de partage sont le rayon ionique, l’électronégativité, la force ionique et la concentration molaire. Un modèle mathématique a permis de prédire le coefficient de partage des ions dans ce système. Dans le but d’expliquer l’absorption des ions par la phase solide, une simulation par dynamique moléculaire a été menée sur un système pectine-eau-sels. Quatre systèmes ont été utilisés. Les résultats obtenus ont montré que la nature ionique influencent la nature et le nombre d’interaction entre pectine-ion et eau-ion et donc offrent une description explicite des phénomènes de transferts et distribution des ions dans le système solide/liquide

Inorganic contaminants, while transported through the bentonite layer, are chemically adsorbed onto the particle surfaces and exhibit a delay in solute breakthrough in hydraulic barriers. Transport of inorganic leachate contaminants through bentonite occurs by advection, diffusion or a combination of these two mechanisms. During the process of chemical solute transport through low permeability bentonite, the amount of cation exchange on the clay particle surface is directly related to the cation exchange capacity (CEC) of montmorillonite and other mineral constituents. The process of diffusion and advection of various inorganic leachate contaminants through bentonite is thoroughly investigated in this study. Diffusion characteristics are of specific interest as they have a prominent effect on the long term properties of bentonite compared to advection. This is mostly true if the hydraulic conductivity of the material is less than 10-8 cm/s and if the thickness of the barrier is small. Chemical reactions in the form of cationic exchange on the clay particle surfaces has been incorporated in the analysis of the diffusion process. Adsorption-desorption (sorption) reactions of chemical compounds that influence the concentrations of inorganic leachates during transport in bentonite clay have been modeled using the Fick's fundamental diffusion theory. Partition coefficients of the solutes in pore space, which affect the retardation factor of various individual ions of chemical solutions, have been investigated during transient diffusion and advection processes. Several objectives have been accomplished during this research study. An evaluation has been carried out of the hydraulic conductivity of bentonite with respect to single species salts and various combinations of electrolyte solutions. Diffusion properties of inorganic leachates through bentonite have been characterized in terms of apparent and effective diffusion coefficients. Time-dependent behavior of the diffusive ions has been analyzed in order to determine the total retention capacity of bentonite before electrical conductivity breakthrough and steady-state chemical stability are reached. An analytical solution of the attenuation of various inorganic ions concentrations through bentonite has been developed. Finally, recommendations were made for landfill liners exposed to highly concentrated inorganic leachates.

Thesis (PhD (Pharmaceutics))--PU for CHE, 1999.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with high levels of tumour necrosis factor-alpha (TNF-a) in synovial fluid and synovial tissue (Saxne et al., 1989). Thalidomide is a proven inhibitor of the biological synthesis of TNF-a (Sampaio et al., 1991) and is believed to rely on this action for its suppression of the wasting of tissue which accompanies RA. Oral administration of thalidomide has proven to be effective in RA, but unacceptable side effects are easily provoked (Gutierrez-Rodriguez, 1984). Administration of thalidomide via the dermal route can down-regulate TNF-a production in and around the affected joint, and this without raising the systemic blood level to a problematical level. Based on thalidomide's physicochemical properties, it is unlikely that it can be delivered percutaneously at a dose required for RA. Therefore, we have embraced the idea of using N-alkyl analogues of thalidomide. The most important feature that an analogue of this compound might contribute is decreased crystallinity and increased lipophilicity. Ordinarily both these parameters should favour percutaneous delivery. The current study was primarily aimed at exploring the feasibility of percutaneous delivery of thalidomide and subsequently, three of its odd chain IV-alkyl analogues (methyl, propyl and pentyl) via physicochemical characterization and assessment of their innate abilities to diffuse through skin as an initial step towards developing a topical dosage form for the best compound. The biological activities, more specifically their potential to inhibit the production of TNF-a was determined for thalidomide and its N-alkyl analogues. In order to achieve the objectives, the study was undertaken by synthesizing and determining the physicochemical parameters of thalidomide and its N-alkyl analogues. A high level of crystallinity is expressed in the form of a high melting point and heat of fusion. This limits solubility itself, and thus also sets a limit on mass transfer across the skin. Generally, the greater a drug's innate tendency to dissolve, the more likely it is that the drug can be delivered at an appropriate rate across the skin (Ostrenga et al., 1971). Therefore, the melting points and heats of fusion were determined by differential scanning calorimetry. Aqueous solubility and the partition coefficient (relative solubility) are major determinants of a drug's dissolution, distribution and availability. N-octanollwater partition coefficients were determined at pH 6.4. Solubilities in water, a series of n-alcohols and mixed solvents were obtained, as well as the solubility parameters of the compounds in study. Secondly, in vitro permeation studies were performed from these solvents and vehicles using vertical Franz diffusion cells with human epidermal membranes. Thirdly, tumour necrosis factor-alpha (TNF-a) inhibition activities were assessed for thalidomide and its N-alkyl analogues. By adding a methyl group to the thalidomide structure, the melting point drops by over 100°C and, in this particular instance upon increasing the alkyl chain length to five -CH2- units the melting points decrease linearly. Heats of fusion decreased dramatically upon thalidomide's alkylation as well. Methylation of the thalidomide molecule enhanced the aqueous solubility 6-fold, but as the alkyl chain length is further extended from methyl to pentyl, the aqueous solubility decreased exponentially. The destabilization of the crystalline structure with increasing alkyl chain length led to an increase in lipophilicity and consequently an increase in solubility in nonpolar media. Log partition coefficients increased linearly with increasing alkyl chain length. Solubilities in a series of n-alcohols, methanol through dodecanol, were found to be in the order of pentyl > propyl > methyl > thalidomide. The N-alkyl analogues have more favourable physicochemical properties than thalidomide to be delivered percutaneously. The in vitro skin permeation data proved that the analogues can be delivered far easier than thalidomide itself. N-methyl thalidomide showed the highest steady-state flux through human skin from water, n-alcohols and combination vehicles. Thalidomide and its N-alkyl analogues were all active as TNF-a inhibitors. Finally, active as a TNF-a inhibitor, N-methyl thalidomide is the most promising candidate to be delivered percutaneously for treatment of rheumatoid arthritis, of those studied. / Thesis (PhD (Pharmaceutics))--PU for CHE, 1999.