Formas farmacêuticas de liberação prolongada são especialmente eficazes no controle da hipertensão. A incorporação da furosemida neste tipo de sistema é adicionalmente justificável por se manter as vantagens de um diurético de alça, porém, com efeito menos intenso e mais duradouro, gerando menor desconforto ao paciente crônico e diminuição no número de administrações diárias. Considerando-se a limitada solubilidade da furosemida e as vantagens tecnológicas das ciclodextrinas (CD) e dos comprimidos matriciais hidrofílicos, procuro-se averiguar a influência da β-ciclodextrina (β-CD) ou hidroxipropil-β--ciclodextrina (HP-β-CD), incorporadas às formulações como misturas físicas ou complexadas ao fármaco, no perfil de liberação de comprimidos à base de hidroxipropilmetilcelulose (HPMC), desenvolvidos para modular adequadamente a liberação da furosemida por um período de oito horas. Para tanto, complexos de inclusão foram obtidos por liofilização e caracterizados por análise térmica e espectrofotometria. Comprimidos de 500 mg foram preparados por compressão direta. Mantiveram-se constantes nas formulações: furosemida (10%), HPMC (25%) e agente lubrificante (0,5%), variando-se a concentração do diluente. Avaliou-se, estatisticamente (ANOVA), a influência da adição de β-CD ou HP-β-CD ou lactose, nas eficiências de dissolução (ED) do fármaco. As ED foram calculadas a partir dos perfis de liberação, determinados após submissão dos comprimidos à dissolução, por 8 horas, utilizando-se meio tamponado pH 6,8 ou gradiente de pH. Os mecanismos de liberação foram indiretamente estimados por modelos matemáticos (ordem zero, primeira ordem ou Higuchi). A presença de ciclodextrinas nas formulações, tanto em mistura física quanto complexadas, gerou aumento significativo na velocidade e extensão de liberação da furosemida pelos comprimidos, propiciando cinética de acordo com o modelo de Higuchi. Adicionalmente, a complexação foi capaz de prover uma liberação pH-independente, representando significativa vantagem tecnológica. / Extended release dosage forms are especially effective for hypertension control. Additionally, the advantages of incorporating furosemide in such system is to keep the features of a loop diuretic, however, with a less intense and more lasting effect. Moreover, less discomfort to chronic patients and decreased number of daily administrations could be provided. Considering the limited solubility of furosemide and the technological advantages of cyclodextrins (CD) and hydrophilic matrix tablets, this work evaluates the influence of β-cyclodextrin (β-CD) or hydroxypropyl-β-cyclodextrin (HP-β-CD) on the release profile of hydroxypropylmethylcellulose (HPMC) tablets, aimed to modulate the drug release during an eight hour period The CD were incorporated to the formulations as physical mixtures or complexed with the drug. Thus, inclusion complexes were obtained by freeze-drying and characterized by thermal analysis and spectrophotometry. Tablets of 500 mg were prepared by direct compression. Furosemide (10%), HPMC (25%) and lubricant agent (0,5%) were kept constant in the formulations, varying the diluent concentration. The influence of β-CD or HP-β-CD or lactose addition, on the dissolution efficiency (DE) of the drug, was evaluated statistically by ANOVA. The DE were calculated performing dissolution assays of the tablets for 8 hours, using phosphate buffer at pH 6,8 or pH gradient as milieu. The release mechanisms were indirectly estimated by mathematical models (zero order, first order or Higuchi). The presence of CD in the formulations, even in physical mixture or complexed with the furosemide, demonstrated significant increase of the velocity and extension of the drug release, according to Higuchi\'s model. Nevertheless, the complexation was able to provide a pH-independent release, representing significant technological advantage.

Silicate minerals are the most common mineral group in the earth's crust so it is not surprising that their weathering reactions dominate the chemistry of many earth surface processes. This project used forsterite as a model system to identify the important factors that affect silicate mineral dissolution rates and grain lifetimes in the weathering environment. I determined an empirical rate law for forsterite dissolution of forsterite in oxalic acid solutions: based on a series of 124 semi-batch reactor experiments over a pH range of 0 to 7 and total oxalate concentrations between 0 and 0.35 m at 25°C. These experiments show that oxalate-promoted dissolution rates depend upon both oxalate concentration and pH. I propose a reaction mechanism in which a hydrogen ion and an oxalate ion are simultaneously present in the activated complex for the reaction that releases H4SiO4 into solution. By analogy, I propose that water acts as a ligand in the absence of oxalate. I also ran 82 batch reactor experiments in magnesium and sodium sulfate and magnesium and potassium nitrate solutions. These experiments show that ionic strength up to 12 m, log mMg up to 4 m, and log mSO4 up to 3 m have no effect on forsterite dissolution rates. However, decreasing aH2O slows forsterite dissolution rates. The effect of decreasing dissolution rates with decreasing aH2O is consistent with the idea that water acts as a ligand that participates in the dissolution process.Forsterite dissolution rate data from previously published studies were combined with results from my experiments and regressed to produce rate laws at low and high pH. For pH < 5.05 or and for pH > 5.05 or I then developed a diagram that shows the effect rate-determining variables on the lifetime of olivine grains in weathering environments using these rate laws. / Ph. D.

Fármacos pouco solúveis em água são um dos maiores desafios encontrados em formulação de comprimidos, uma vez que, se não adequadamente formulados, podem apresentar problemas de dissolução e de biodisponibilidade. O presente trabalho teve como objetivo produzir comprimidos de glibenclamida 5 mg (hipoglicemiante oral pouco solúvel) utilizando diferentes processos visando a melhoria da dissolução do fármaco e comparar a liberação in vitro (perfil de dissolução) das formulações entre si, bem como em relação ao medicamento referência no Brasil, Daonil&#174;. Foram obtidas 19 formulações por compressão direta empregando dispersão sólida, complexação com ciclodextrina ou micronização do fármaco. Os comprimidos foram analisados quanto ao aspecto, peso médio, dureza, friabilidade, teor e eficiência de dissolução. Os resultados indicaram que, dentre os processos estudados, a utilização de complexos glibenclamida-&#946;-ciclodextrina e glibenclamida micronizada, promoveram uma melhora da dissolução do fármaco. O superdesintegrante Explocel&#174; promoveu significativa melhoria no perfil de dissolução em todas as formulações em que estava presente. A utilização do complexo glibenclamida-&#946;-ciclodextrina com o Explocel&#174; apresentou perfil de dissolução estatisticamente semelhante ao Daonil&#174;, além de atender aos demais requisitos físico-químicos. / Slightly soluble drugs are one of the largest challenges found in tablet formulation, once, if not appropriately formulated, they can present dissolution and bioavailability problems. The present work had as objective to produce 5 mg glibenclamide (practically insoluble hipoglicemic drug) tablets using different processes which aim at enhancing drug dissolution and to compare the in vitro release (dissolution profile) of these formulations with each other as well as with the reference medicine in Brazil, Daonil&#174;. 19 diferent formulations were obtained through direct compression using solid dispersion, cyclodextrin complexion or micronization of the drug. The tablets were also analyzed in relation to aspect, medium weight, hardness, friability, assay and dissolution eficiency. The results indicated that, among the studied processes, an enhancement of the dissolution rate of the drug have arisen from the use of the glibenclamide-&#946;-cyclodextrin complex and the micronized glibenclamide. The disintegrant Explocel&#174; promoted enhancement in the dissolution rate in all the formulations in which it was present. The use of the glibenclamide-&#946;-cyclodextrin complex with Explocel&#174; have presented the best dissolution profile, statistically similar to Daonil&#174;, besides accomplishing the other physico-chemical requirements.

Fármacos pouco solúveis em água são um dos maiores desafios encontrados em formulação de comprimidos, uma vez que, se não adequadamente formulados, podem apresentar problemas de dissolução e de biodisponibilidade. O presente trabalho teve como objetivo produzir comprimidos de glibenclamida 5 mg (hipoglicemiante oral pouco solúvel) utilizando diferentes processos visando a melhoria da dissolução do fármaco e comparar a liberação in vitro (perfil de dissolução) das formulações entre si, bem como em relação ao medicamento referência no Brasil, Daonil&#174;. Foram obtidas 19 formulações por compressão direta empregando dispersão sólida, complexação com ciclodextrina ou micronização do fármaco. Os comprimidos foram analisados quanto ao aspecto, peso médio, dureza, friabilidade, teor e eficiência de dissolução. Os resultados indicaram que, dentre os processos estudados, a utilização de complexos glibenclamida-&#946;-ciclodextrina e glibenclamida micronizada, promoveram uma melhora da dissolução do fármaco. O superdesintegrante Explocel&#174; promoveu significativa melhoria no perfil de dissolução em todas as formulações em que estava presente. A utilização do complexo glibenclamida-&#946;-ciclodextrina com o Explocel&#174; apresentou perfil de dissolução estatisticamente semelhante ao Daonil&#174;, além de atender aos demais requisitos físico-químicos. / Slightly soluble drugs are one of the largest challenges found in tablet formulation, once, if not appropriately formulated, they can present dissolution and bioavailability problems. The present work had as objective to produce 5 mg glibenclamide (practically insoluble hipoglicemic drug) tablets using different processes which aim at enhancing drug dissolution and to compare the in vitro release (dissolution profile) of these formulations with each other as well as with the reference medicine in Brazil, Daonil&#174;. 19 diferent formulations were obtained through direct compression using solid dispersion, cyclodextrin complexion or micronization of the drug. The tablets were also analyzed in relation to aspect, medium weight, hardness, friability, assay and dissolution eficiency. The results indicated that, among the studied processes, an enhancement of the dissolution rate of the drug have arisen from the use of the glibenclamide-&#946;-cyclodextrin complex and the micronized glibenclamide. The disintegrant Explocel&#174; promoted enhancement in the dissolution rate in all the formulations in which it was present. The use of the glibenclamide-&#946;-cyclodextrin complex with Explocel&#174; have presented the best dissolution profile, statistically similar to Daonil&#174;, besides accomplishing the other physico-chemical requirements.

L’objectif de cette thèse est de quantifier l’évolution de la surface réactive d’un silicate modèle (orthose) lors de son altération hydrothermale et estimer son impact sur la cinétique réactionnelle. L’étude porte sur : (1) l’influence de la présence de couverture de phases secondaires à même la surface de l’orthose, (2) l’impact de l’anisotropie de la structure cristalline de l’orthose et (3) l’effet de la formation de puits de corrosion en surface. Les résultats expérimentaux et numériques mettent en évidence que la vitesse de dissolution de l’orthose et son évolution au cours du temps dépendent essentiellement de sa morphologie.Certaines faces cristallines se dissolvent 10 fois plus rapidement que d’autres, entraînant une augmentation de la proportion de faces rapides au cours du processus et une élévation, jusqu’à un ordre de grandeur, de la vitesse de dissolution globale de l’orthose. Ces résultats ouvrent d’importantes pistes de réflexion sur la méthode adéquate pour rendre compte des cinétiques des interactions fluide/roche sur le terrain ainsi que sur la signification des lois de vitesse et des mécanismes réactionnels déterminés à partir d’expériences sur poudre. / This thesis aims at quantifying the reactive surface area evolution of dissolving K- feldspar, and evaluating the impact on the dissolution kinetics during its alteration in geothermal context. The study focuses on : (1) the influence of secondary coatings on the orthoclase surface, (2) the impact of the anisotropic crystalline structure of orthoclase and (3) the effect of etch pit formation on the mineral surface. Experimental and numerical results highlight that the orthoclase dissolution rate and its evolution over time mainly depends onits morphology. Some orthoclase faces dissolve 10 times faster than others, resulting in an increase of the surface proportion of rapid vs. slow dissolving faces during the process and the increase of up to an order of magnitude of the overall orthoclase dissolution rate. These results question the significance of rate laws and reaction mechanisms determined from powder experiments and the pave to new approaches for investigating mineral reactivity.

>Magister Scientiae - MSc / Fly ash is the most abundant of the waste materials generated from coal combustion in coal-fired power stations. South Africa uses more than 100 million tonnes of low grade bituminous coal annually to produce cheap electricity thereby generating huge amounts of fly ash each year. The disposal of fly ash has been a major concern to the world because of its potential environmental impact due to the possible leaching of the toxic elements contained in fly ash. This study centres on the chemical characterization and leaching behaviour of the fly ashes generated from SASOL Synfuels and ESKOM power station at Secunda and Tutuka in South Africa respectively. The aim is to understand the composition of the fly ashes and to determine the leachability of species from the ashes in order to predict the environmental effect of the different ash handling system of the coalfired stations (wet disposal system in Secunda and dry disposal system in Tutuka). Several leaching methods were employed in this study in order to develop a methodology for evaluating and modelling ash system and were able to discriminate between ash types and model ash handling system. Fly ashes from the two South African coal-fired stations were subjected to total acid-digestion and XRF analyses in order to determine the total amounts of major and minor species contained in the fly ashes. The total acid-digestion test and the XRF analysis revealed that the major species such as Al, Si, Ca, Na, Mg, K, Sr, Ba and S04, and minor species such as Fe, Ti, V, Mn, Cr, Ni and Cu were present in both fly ashes in fairly similar concentrations. The mineralogical characterization by XRD of Secunda and Tutuka fly ashes revealed mullite and quartz as the major mineral phases with minor peaks of CaO and calcite. Several leaching tests and different leaching conditions were employed in this study in order to develop a standardized replicable methodology for environmental impact assessment and for modelling the impact of different ash handling scenarios. The fly ashes were exposed to these different leaf leachant of different pHs on the leachability of species from the fly ashes. To achieve this, DIN-S4, TCLP and ANC tests were employed. The natural pH of the fly ash leachates were very high ranging between 12.56 and 13.08. The DIN-S4 leaching test revealed that the easily soluble species of the fly ashes include Ca, Mg, Na, K and S04 and various toxic elements. The leachates from the TCLP test recorded higher concentrations of Ca, Mg, Na, K and S04 which was attributed to the slight decrease in the pH due to the addition of a acidic leachant with a pH of 2.88. Comparison of the amount leached (DIN-S4) from the fly ashes with the total concentrations of each of the components of the fly ashes (determined by the total acid-digestion), the percentage of each of the readily soluble species ranged from 15-24.23% for Ca, 0.23-0.45% for K, 0.58-0.82% for Na, 0.0047-0.007% for Mg, 0.96-3.33% for Ba and 0.012-1.51 % for S04 per dry mass of each component in the fly ash. The ANC test revealed the effect of a leachant of specified pH on the release of species from the fly ashes with concentrations of the major and minor species leached out of the fly ashes found to be higher than the concentrations released into the leachates when DIN-S4 and TCLP test were considered at specific pH and showed the pH dependence of the solubility and release of species. These tests also showed the effect of the liquid to solid ratio upon leachability of species. In addition to the batch leaching tests mentioned above, dissolution kinetics and up-flow percolation tests were carried out on the fly ashes to determine the leaching behaviours of the fly ashes over time and the factors controlling the release of species from the fly ashes in the long term. The dissolution kinetics test was done for an extended period of 60 days with recycle of the leachant and the up-flow percolation test was carried out with constant leachant renewal until a liquid/solid ratio of 20 was attained (:::::;9d0ays). The geochemical computer code PHREEQC and MINTEQ database was used for geochemical modelling of the leachates at various reaction times and LIS ratios. The geochemical modelling results revealed that the release of the species from the fly ashes is controlled by the solubility of mineral phases in many case except for Na. The release of Ca, S04, Mg, Ba and Sr in the leachates of the fly ashes were predicted to be controlled by portlandite, gypsum, brucite, barite and celestite respectively while birnessite, magnetite, BaCr04, CaMo04 and Ba(As04h were predicted to be the mineral phases controlling the release of Mn, Fe, Cr, Mo and As respectively. The pH of the leachates plays a significant role in the leaching of both major and minor species from the fly ashes. The concentrations of species leached into solution at low pH (ANC and TCLP) were higher than the concentrations released at high pH (DIN-S4, dissolution kinetics and up-flow percolation tests). The amounts of the toxic elements such as As, Se, Cd, Cr and Pb that leached out of the fly ashes when in contact with demineralized water (DIN-S4) were very low and below the target water quality range (TWQR) of South African Department of Water Affairs and Forestry (DWAF), but the amounts of As and Se leached out by acidic leachant applied in the TCLP test and at lower pH ranging between 8 and 10 the case of the ANC test were slightly higher than the TWQR, which is an indication that the pH of the leaching solution and the contact time playa significant role on the leaching of species out of the fly ashes. This study revealed that the leaching of species from the fly ashes depends on various factors which include: physical and chemical characteristics and mineralogical composition of the fly ashes, the total concentrations of species in the ash, the rate of flow through the ash system and more importantly the pH of the leachant to which the ash system is exposed to. The results of different experiments and analysis carried out on the two South African fly ashes (Secunda and Tutuka fly ashes) showed that, despite the high concentrations of soluble species or leachable elements in the fly ashes, the leaching of major, minor and trace elements into the soils and the groundwater could be minimized if certain conditions such as avoiding acidic precipitation that could reduce the pH of the ash system are adhered to. The leaching trends of the species and the geochemical modelling data also showed that the formation of secondary mineral phases could reduce the release of toxic elements, the release of which would require aggressive low pH leachants, high flow rate, high recharge and long-term leaching for the dissolution of the formed mineral phases. In conclusion, the combination of the leaching tests employed in this study gives information on the leaching behaviour of the Secunda and Tutuka fly ashes and the factors controlling the leaching of the elements from the fly ashes. This study has been able to show that elements are leached out of the fly ashes at both alkaline and acidic pH. It is also revealed in the study that the disposal techniques employed by the coal-fired stations which were simulated by using the dissolution kinetics and up-flow percolation tests are adequate methods for modelling of the ash disposal scenario. These two methods show that the dry disposal system at Tutuka will encourage equilibration of the ash/water system thereby facilitating the precipitation of mineral phases that could control the release of both major and minor species from the fly ash, whereas the wet ashing system at Secunda may expose the ash to sufficient flow to rapidly leach species out into the environment.

Uganda is well endowed with economic quantities of mineral salts present in the interstitial brines and evaporite deposits of Lake Katwe, a closed (endorheic) saline lake located in the western branch of the great East African rift valley. Currently, rudimentally and artisanal methods continue to be used for salt extraction from the lake raw materials. These have proved to be risky and unsustainable to the salt miners and the environment and they have a low productivity and poor product quality. This work involves the investigation of the salt raw materials that naturally occur in the brines and evaporites of Lake Katwe. The purpose is to propose strategies for the extraction of improved salt products for the domestic and commercial industry in Uganda. The literature concerning the occurrence of salt and the most common available technologies for salt extraction was documented. Also, field investigations were undertaken to characterize the salt lake deposits and to assess the salt processing methods and practices. The mineral salt raw materials (brines and evaporites) were characterized to assess their quality in terms of the physical, chemical, mineralogical, and morphological composition through field and laboratory analyses. An evaluation of the potential of future sustainable salt extraction from the lake deposits was done through field, experimental, and modeling methods. Moreover, the mineral solubilities in the lake brine systems and dissolution kinetics aspects were investigated. The results reveal that the salt lake raw materials contain substantial amounts of salt, which can be commercialized to enable an optimum production. The brines are highly alkaline and rich in Na+, K+, Cl-, SO42-, CO32-, and HCO3-. Moreover, they contain trace amounts of Mg2+, Ca2+, Br-, and F-. The lake is hydro-chemically of a carbonate type with the brines showing an intermediate transition between Na-Cl and Na-HCO3 water types. Also, the evaporation-crystallization is the main mechanism controlling the lake brine chemistry. These evaporites are composed of halite mixed with other salts such as hanksite, burkeite, trona etc, but with a composition that varies considerably within the same grades. The laboratory isothermal extraction experiments indicate that various types of economic salts such as thenardite, anhydrite, mirabilite, burkeite, hanksite, gypsum, trona, halite, nahcolite, soda ash, and thermonatrite exist in the brine of Lake Katwe. In addition, the salts were found to crystallize in the following the sequence: sulfates, chlorides, and carbonates. A combination of results from the Pitzer’s ion-interaction model in PHREEQC and experimental data provided a valuable insight into the thermodynamic conditions of the brine and the sequence of salt precipitation during an isothermal evaporation. A good agreement between the theoretical and experimental results of the mineral solubilities in the lake brine systems was observed with an average deviation ranging between 8-28%. The understanding of the mineral solubility and sequence of salt precipitation from the brine helps to control its evolution during concentration. Hence, it will lead to an improved operating design scheme of the current extraction processes. The dissolution rate of the salt raw materials was found to increase with an increased temperature, agitation speed and to decrease with an increased particle size and solid-to-liquid ratio. Moreover, the Avrami model provided the best agreement with the obtained experimental data (R2 = 0.9127-0.9731). In addition, the dissolution process was found to be controlled by a diffusion mechanism, with an activation energy of 33.3 kJ/mol. Under natural field conditions, the evaporative-crystallization process at Lake Katwe is influenced by in-situ weather conditions. Especially, the depth of the brine layer in the salt pans and the temperature play a significant role on the brine evaporation rates. With the optimal use of solar energy, it was established that the brine evaporation flux can be speeded up in the salt pans, which could increase the production rates. Moreover, recrystallization can be a viable technique to improve the salt product purity. Overall, it is believed that the current work provides useful information on how to exploit the mineral salts from the salt lake resources in the future. / <p>QC 20151217</p>

O estudo de dissolução in vitro é uma ferramenta importante utilizada para o controle de qualidade lote-a-Iote dos medicamentos, como guia no desenvolvimento de novas formulações e para assegurar a qualidade e performance do produto após certas alterações. O itraconazol é um fármaco com baixa solubilidade em meio aquoso (classe 11), dessa forma, alguns problemas de solubilidade podem ser detectados no ensaio de dissolução. A proposta deste trabalho foi a realização de uma avaliação biofarmacêutica in vitro de cápsulas contendo péletes de itraconazol comercializadas no mercado brasileiro por laboratórios farmacêuticos e farmácias magistrais. O medicamento de referência, registrado com o nome de Sporanox® (Janssen-Cilag), uma formulação genérica, duas formulações similares e quatro formulações magistrais, foram submetidas a ensaios de doseamento, perfil de dissolução, eficiência de dissolução, cinética de dissolução, fator de diferença (f1) e fator de semelhança (f2). Os resultados demonstraram diferenças de liberação entre as formulações sugerindo que as mesmas não são equivalentes ao medicamento de referência. / Dissolution testing is an important tool used as a quality control procedure in pharmaceutical production, as guide in the development of new formulations and to assure the quality and performance of the product after certain modifications. Itraconazol is a poorly water-solubility drug (class 11) and the dissolution studies are very important to detect solubility problems. The purpose of this work was the in vitro biopharmaceutical evaluation of capsules containing Itraconazole pellets manufactured by Brazilian pharmaceutical laboratories and compounding pharmacies. The reference product, registered as Sporanox® (Janssen-Cilag), a generic product, a similar formulation and four compounding formulations were submitted to assay, dissolution profile, dissolution efficiency, dissolution kinetics, difference factor (f1) and similarity factor (f2). The results demonstrated different releases among the formulations suggesting that they are not equivalent to the reference product.

O estudo de dissolução in vitro é uma ferramenta importante utilizada para o controle de qualidade lote-a-Iote dos medicamentos, como guia no desenvolvimento de novas formulações e para assegurar a qualidade e performance do produto após certas alterações. O itraconazol é um fármaco com baixa solubilidade em meio aquoso (classe 11), dessa forma, alguns problemas de solubilidade podem ser detectados no ensaio de dissolução. A proposta deste trabalho foi a realização de uma avaliação biofarmacêutica in vitro de cápsulas contendo péletes de itraconazol comercializadas no mercado brasileiro por laboratórios farmacêuticos e farmácias magistrais. O medicamento de referência, registrado com o nome de Sporanox® (Janssen-Cilag), uma formulação genérica, duas formulações similares e quatro formulações magistrais, foram submetidas a ensaios de doseamento, perfil de dissolução, eficiência de dissolução, cinética de dissolução, fator de diferença (f1) e fator de semelhança (f2). Os resultados demonstraram diferenças de liberação entre as formulações sugerindo que as mesmas não são equivalentes ao medicamento de referência. / Dissolution testing is an important tool used as a quality control procedure in pharmaceutical production, as guide in the development of new formulations and to assure the quality and performance of the product after certain modifications. Itraconazol is a poorly water-solubility drug (class 11) and the dissolution studies are very important to detect solubility problems. The purpose of this work was the in vitro biopharmaceutical evaluation of capsules containing Itraconazole pellets manufactured by Brazilian pharmaceutical laboratories and compounding pharmacies. The reference product, registered as Sporanox® (Janssen-Cilag), a generic product, a similar formulation and four compounding formulations were submitted to assay, dissolution profile, dissolution efficiency, dissolution kinetics, difference factor (f1) and similarity factor (f2). The results demonstrated different releases among the formulations suggesting that they are not equivalent to the reference product.

Discrete and Continuous spatial encoding methods are described with details of understanding principles and practical implications. Step by step experimental op- timization procedure of these methods to achieve slice selection are also discussed. In the subsequent chapters we use these methods for different applications. Spin-lattice relaxation parameters of NMR active nuclei provide valuable infor- mation on molecular dynamics. Single scan selective excitation methods of mea- surement of T1 result in significant reduction of time compared to the standard inversion recovery method and are attractive tools of applications in `Real time' NMR investigations of biological and chemical processes. It is shown here that the addition of the gradient echo following the selective excitation not only significantly improves the S/N ratio, but also makes GESSIR a versatile pulse sequence. Using this sequence, T1 values ranging from 2 s to 56 s have been measured with accuracy comparable to the standard IR experiment. This indicates that it is possible to utilize GESSIR for a wide range of molecules containing protons and hetero nuclei with medium to long T1 relaxation times as a routine NMR technique. The utility of the technique for studying other relaxation parameters has also been demonstrated. It may be mentioned that for measurement of relaxation parameters routinely, a few well-chosen points are enough. A fine selection of large number of experimental points could be useful when high accuracy is required or Chapter 3. GESSIR 91 for applications where certain property of the system investigated is changing in a continuous manner spatially and requires large number of slices to be selected as discussed in the next chapter. The long duration of time-honored two dimensional experiments is reduced to fraction of seconds by employing the ultrafast encoding experiments. Main com- plications in making the UF experiments available for routine use were the limited spectral widths and resolution in both UF and conventional dimensions. Various developments have been made in the path of improvements in increasing the spectral width in UF dimension. Of these, two experimental methods that are already proposed, namely the folding of peaks into the observable spectral window and the interleaved acquisition which doubles the spectral widths in both dimensions. The integration of covariance processing with ultrafast technique yields better correlated spectrum with considerable improvement in resolution. The effectiveness of the new processing is demonstrated for UF COSY experiments which can be easily extended to other ultrafast homonuclear experiments like TOCSY, NOESY as well as multi dimensions. The proposed processing method is an initial step to work on improving resolutions of UF data and making the ease of applicability of ultrafast spectroscopy as a routine multidimensional NMR. At the same time of this work W. Qui et.al [268] proposed a processing method based on covariance and pattern recognition for improving resolutions of spatially encoded data. They used pattern recognition algorithm also for avoiding the artifacts due to very low resolution data available with the UF experiment. They implemented the method UF TOCSY spectra and shown resolution improvement with the covariance pro- cessing for relatively more number of detection gradients which is many times hardware limited. Our method of covariance data processing is essentially same as that of Qui, less number of acquisition gradients were used in our processing, linear prediction and apodization concepts were utilized and the artifacts arise due mismatch of datas with positive and negative acquisition gradients are minimized by shifting one the data. In conclusion new methods of processing/the combination of various processing methods of the ultrafast data have the scope of improving the quality of ultrafast NMR spectra.