Power transmission systems frequently experience new power flow pattern due to several factors that increase uncertainties in the system. For instance, load shape uncertainty, uncertainty due to penetration of renewable sources, changing standards, and energy de-regulation threaten the reliability and security of power transmission systems. This demands for more rigorous analysis and planning of power transmission systems. Stability issues in power transmission system are more pronounced with the penetration of utility-scale Photo-Voltaic (PV) sources. Synchronous generators provide inertia that helps in damping oscillations that arise due to fluctuations in the power system. Therefore, as PV generators replace the conventional synchronous generators, power transmission systems become vulnerable to these abnormalities. In this thesis, we study the effect of reduced inertia due to the penetration of utility-scale PV on the transient stability of power transmissions systems. In addition, the effect of increased PV penetration level in the system during normal operating condition is also analyzed. The later study illustrates that the PV penetration level and the placement of PV sources play crucial roles in determining the stability of power transmission systems. Given increasing uncertainties in power transmission systems, there is a need to seek an alternative to deterministic planning approach because it inherently lacks capability to cover all the uncertainties. One practical alternative is the probabilistic planning approach. In probabilistic planning approach, an analysis is made with a wide variety of scenarios by considering the probability of occurrence of each scenario and the probability of contingencies. Then, the severity of the contingencies risk associated with each planning practice is calculated. However, due to the lack of techniques and tools to select wide varieties of scenarios along with their probability of occurrence, the probabilistic transmission planning approach has not been implemented in real-world power transmission systems. This thesis presents a technique that can select wide varieties of scenarios along with their probability of occurrence to facilitate probabilistic planning in Electricity Reliability Council of Texas (ERCOT) systems. / Master of Science / Reliability of power transmission systems are threatened due to the increasing uncertainties arising from penetration of renewable energy sources, load growth, energy de-regulation and changing standards. Stability issues become more prevalent than in past due to increasing load growth as the demand for reactive power increases. Several researchers have been studying the impact of increased load growth and increased penetration of renewables on the dynamic stability of the distribution system. However, far less emphasis has been given to the power transmission system. This thesis presents the transient stability analysis of power transmission systems during overloading conditions. Our study also facilitates identification of weak areas of the transmission system during overloading condition. In addition, the impact of replacing conventional synchronous generator by Photovoltaics (PV) on voltage stability of the system is also analyzed. With increasing uncertainties in transmission systems, it is necessary to carefully analyze a wide variety of scenarios while planning the system. The current approach to transmission planning i.e., the deterministic approach does not sufficiently cover all the uncertainties. This has imposed the need for the probabilistic transmission planning approach where the overall system is planned based on the analysis of wide varieties of scenarios. In addition, by considering the probability of occurrence of a scenario, the probability of contingencies and severity of contingencies risk associated with each planning practice is calculated. However, there is no well-established approach that is capable of selecting wide varieties of scenarios based on their probability of occurrence. Due to this limitation, probabilistic approach is not widely implemented in real-world power transmission systems. To address this issue, this thesis presents a new technique, based on K-means clustering, to select scenarios based on their probability of occurrence.

This diploma thesis is focused on determining the physico-chemical stability of toothpastes. It is divided into theoretical and practical part. The theoretical part of the work deals with toothpastes, their short history and composition. Stability studies and methods of stability analysis are described below. In the practical part were performed long-term and accelerated stability studies on anhydrous toothpastes, on water-based toothpastes and on toothpastes based on sodium bicarbonate. The physical stability of the products was evaluated by monitoring the appearance and color visually and odor sensory, the pH value using a pH meter and the viscosity with a rotational viscometer. Chemical stability was monitored by determining the free fluorine content by ion chromatography and by ion-selective electrode, total phosphates and potassium also by ion chromatography, sodium bicarbonate by titration, soluble zinc by atomic absorption spectrometry and water activity was also monitored.

A síndrome da imunodeficiência adquirida é causada pelo vírus da imunodeficiência humana e é caracterizada por provocar depleção física e funcional do sistema imune do organismo, através da infecção citopática de células CD4+. Muitos fármacos anti-retrovirais tem sido desenvolvidos e estão disponíveis comercialmente. Para atuar no controle de qualidade de medicamentos deve-se continuamente estudar o desenvolvimento e a validação de novas metodologias para quantificação de fármacos, para serem aplicadas nos estudos de estabilidade de formulações farmacêuticas e na análise de produtos de degradação. Neste trabalho foram utilizadas duas técnicas analíticas, a espectrofotometria direta no UV/VIS e a cromatografia líquida de alta eficiência (CLAE), para a determinação quantitativa de zidovudina (AZT) e estavudina (d4T).em medicamentos. Ambos os métodos foram validados com relação à linearidade, exatidão, precisão, especificidade e limite de detecção e quantificação. O método validado para a CLAE foi também empregado para a determinação quantitativa da timina, produto de degradação do AZT e da d4T. A metodologia validada por CLAE foi utilizada na realização de estudos de estabilidade acelerada dos anti-retrovirais contidos nas diferentes preparações farmacêuticas. Realizou-se o estudo da estabilidade em três diferentes condições: temperatura ambiente, 40 oC / 75% UR e 50 oC / 90% UR. Tanto a zidovudina (Fabricante A) e estavudina (Fabricante B) apresentaram decaimento cinético de zero ordem com prazos de validade a 50 oC / 90% UR de 10, 3 e 2 meses, respectivamente. / The acquired immunodeficiency syndrome is characterized by causing physical and functional depletion of the organism’s immune system, through the cytophatic infection of CD4+ cells. Several antiretroviral drugs has been developed and commercially made available. In order to assure the quality control of drugs it is necessary to develop and validate new analytical methodologies to perform the quantitative determination of drugs and stability studies of pharmaceutical formulations by determining the drug itself and its degradation products. In this research two analytical techniques, direct UV/VIS spectrophotometry and high performance liquid chromatography (HPLC), were used for the quantitative determination of zidovudine (AZT) and stavudine (d4T) in pharmaceutical preparations. Both methods were validated and parameters like linearity, precision, accuracy, specificity, limit of detection and limit of quantification, were determined. The validated HPLC method was also applied for quantitative determination of timine, a degradation product of AZT and d4T. The validated HPLC method was applied to accelerate stability studies of AZT and d4T in different pharmaceutical preparations. The stability studies were performed at three different conditions: room temperature, 40 oC / 75% RH and 50 oC / 90% RH. Both AZT and d4T (Industry A) and d4T (Industry B) pharmaceutical preparations presented a zero order degradation reaction. The three formulations presented a shelf-life of 10, 3 and 2 months, respectively, at 50 oC / 90% RH.

A síndrome da imunodeficiência adquirida é causada pelo vírus da imunodeficiência humana e é caracterizada por provocar depleção física e funcional do sistema imune do organismo, através da infecção citopática de células CD4+. Muitos fármacos anti-retrovirais tem sido desenvolvidos e estão disponíveis comercialmente. Para atuar no controle de qualidade de medicamentos deve-se continuamente estudar o desenvolvimento e a validação de novas metodologias para quantificação de fármacos, para serem aplicadas nos estudos de estabilidade de formulações farmacêuticas e na análise de produtos de degradação. Neste trabalho foram utilizadas duas técnicas analíticas, a espectrofotometria direta no UV/VIS e a cromatografia líquida de alta eficiência (CLAE), para a determinação quantitativa de zidovudina (AZT) e estavudina (d4T).em medicamentos. Ambos os métodos foram validados com relação à linearidade, exatidão, precisão, especificidade e limite de detecção e quantificação. O método validado para a CLAE foi também empregado para a determinação quantitativa da timina, produto de degradação do AZT e da d4T. A metodologia validada por CLAE foi utilizada na realização de estudos de estabilidade acelerada dos anti-retrovirais contidos nas diferentes preparações farmacêuticas. Realizou-se o estudo da estabilidade em três diferentes condições: temperatura ambiente, 40 oC / 75% UR e 50 oC / 90% UR. Tanto a zidovudina (Fabricante A) e estavudina (Fabricante B) apresentaram decaimento cinético de zero ordem com prazos de validade a 50 oC / 90% UR de 10, 3 e 2 meses, respectivamente. / The acquired immunodeficiency syndrome is characterized by causing physical and functional depletion of the organism’s immune system, through the cytophatic infection of CD4+ cells. Several antiretroviral drugs has been developed and commercially made available. In order to assure the quality control of drugs it is necessary to develop and validate new analytical methodologies to perform the quantitative determination of drugs and stability studies of pharmaceutical formulations by determining the drug itself and its degradation products. In this research two analytical techniques, direct UV/VIS spectrophotometry and high performance liquid chromatography (HPLC), were used for the quantitative determination of zidovudine (AZT) and stavudine (d4T) in pharmaceutical preparations. Both methods were validated and parameters like linearity, precision, accuracy, specificity, limit of detection and limit of quantification, were determined. The validated HPLC method was also applied for quantitative determination of timine, a degradation product of AZT and d4T. The validated HPLC method was applied to accelerate stability studies of AZT and d4T in different pharmaceutical preparations. The stability studies were performed at three different conditions: room temperature, 40 oC / 75% RH and 50 oC / 90% RH. Both AZT and d4T (Industry A) and d4T (Industry B) pharmaceutical preparations presented a zero order degradation reaction. The three formulations presented a shelf-life of 10, 3 and 2 months, respectively, at 50 oC / 90% RH.

<p>In conclusion, the results obtained firstly indicated that the BP, EMEA and WHO were in fairly good agreement on the criteria and specifications that can be used to assesses the pharmaceutical quality of a traditional plant medicine such as Phela. Secondly, the Phela plant powders were found to have acceptable pharmaceutical properties that did not complicate or adversely affected the capsule manufacture. Thirdly, the Phela capsules produced were generally of acceptable pharmacopoeial standard. Fourthly, HPLC fingerprinting and pattern recognition analysis proved useful to examine the chemical stability of selected marker compounds of Phela and indicated that the capsules had no practical shelf life under elevated temperature and humid conditions. Overall, the Phela capsules should thus be suitable for use in a short time clinical trial, but for use in a long period trial the long term stability of the Phela capsules under ambient conditions must still be confirmed.</p>

<p>In conclusion, the results obtained firstly indicated that the BP, EMEA and WHO were in fairly good agreement on the criteria and specifications that can be used to assesses the pharmaceutical quality of a traditional plant medicine such as Phela. Secondly, the Phela plant powders were found to have acceptable pharmaceutical properties that did not complicate or adversely affected the capsule manufacture. Thirdly, the Phela capsules produced were generally of acceptable pharmacopoeial standard. Fourthly, HPLC fingerprinting and pattern recognition analysis proved useful to examine the chemical stability of selected marker compounds of Phela and indicated that the capsules had no practical shelf life under elevated temperature and humid conditions. Overall, the Phela capsules should thus be suitable for use in a short time clinical trial, but for use in a long period trial the long term stability of the Phela capsules under ambient conditions must still be confirmed.</p>

A estabilidade é um importante parâmetro para avaliar a qualidade, segurança e eficácia exigidas para o registro sanitário de produtos farmacêuticos. A determinação deste parâmetro fundamenta-se não apenas no cumprimento de exigências legais, mas, também, na preocupação com a saúde pública, uma vez que a instabilidade pode estar relacionada à perda do efeito terapêutico ou à exposição do consumidor aos efeitos tóxicos de produtos de degradação. Vários países publicaram diretrizes para a avaliação da estabilidade farmacêutica. No Brasil, os estudos de estabilidade devem ser conduzidos segundo a Guia para Realização de Estudos de Estabilidade, publicada na Resolução-RE n.° 01, de 29 de julho de 2005. No presente trabalho, esta Guia foi avaliada nos aspectos considerados essenciais para obtenção de dados válidos sobre estabilidade. As condições de temperatura e umidade relativa predominantes no Brasil foram determinadas a fim de validar a condição de armazenamento definida na Guia, 30 °C ± 2 °C e 75 % ± 5 % de UR, para a condução do estudo de estabilidade de longa duração. Os resultados obtidos demonstram que a temperatura de 30 °C é adequada para a determinação da estabilidade de produtos farmacêuticos, entretanto, a umidade relativa, fixada em 75 %, não cobre todas as capitais brasileiras. Foi observado, com base na revisão bibliográfica, que existem algumas diferenças entre a Guia e as diretrizes estudadas e que a Guia apresenta alguns aspectos insuficientes que podem influenciar a determinação da estabilidade e do prazo de validade dos medicamentos objetos de registro na ANVISA. Estes aspectos foram discutidos criticamente e sugestões foram propostas a fim de subsidiar futuras alterações da Guia para Realização de Estudos de Estabilidade. / The stability is an important parameter to evaluate the demanded quality, security and effectiveness for the sanitary register of pharmaceutical products. The evaluation of this parameter is based not only on the fulfilment of legal requirements but also in the concern with the public health, once the instability can be related to the loss of the therapeutical effect or to the exposition of the consumer to the toxic effects of degradation products. Several countries had published guidelines for the evaluation of the pharmaceutical stability. In Brazil, the stability studies must be lead according to Guide for Accomplishment of Stability Studies, published in Resolução-RE n.º 01, of July 29th 2005. In the present work, this Guide had been evaluated in the aspects considered essential for attainment of the stability valid data. The temperature and predominant relative humidity conditions in Brazil had been determined in order to validate the storage condition defined in the Guide (30 °C ± 2 °C e 75 % ± 5 % de UR) for the conduction of the long term stability study. The obtained results demonstrate that 30 ºC is the adjusted temperature for the determination of the stability of pharmaceutical products, however, 75 % of UR, have not covered all the Brazilian capitals. It was observed, on the basis of the bibliographical revision, that there are some differences between the Guide and the guidelines studied, and the Guide presents some insufficient aspects that can influence the determination of the stability and the expiration date of drugs products objects of register in the ANVISA. These aspects had been argued critically and suggestions had been proposed in order to subsidize future alterations of the Guide for Accomplishment of Stability Studies.

Made available in DSpace on 2014-06-11T19:25:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-01-21Bitstream added on 2014-06-13T19:32:33Z : No. of bitstreams: 1 correa_jcr_me_arafcf.pdf: 630725 bytes, checksum: 5a65d5833cac2449eb1b9928587306b1 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Universidade Estadual Paulista (UNESP) / O antifúngico fluconazol é um fármaco sintético, desenvolvido na década de 1980, e o primeiro a integrar a classe dos triazóis. Este trabalho teve como objetivo desenvolver métodos analíticos seletivos e indicativos de estabilidade para fluconazol na forma de cápsulas, incluindo métodos físico-químicos e microbiológicos, realizar estudos de dissolução e de estabilidade. Os métodos de análise quantitativos empregados e validados foram: (i) espectrofotometria derivada de primeira ordem no UV a 268 nm, na faixa de concentração de 150–350 μg/mL, o teor médio nas cápsulas encontrado foi de 96,42 %; (ii) CLAE, coluna de C18 e fase móvel composta por metanol:água (60:40, V/V), o teor médio obtido foi de 97,35 %; (iii) determinação da potência microbiológica, pelo método de difusão em ágar cilindros em placa, utilizando cepas de /Candida albicans/, em que a atividade média do fluconazol em cápsulas foi 88,96%. Todos esses métodos foram validados e apresentaram ótima seletividade, precisão e exatidão. O método por CLAE é capaz de separar o fármaco de seu produto de degradação. O teste de dissolução foi desenvolvido e validado utilizando HCl 0,1 /M/ como meio de dissolução e cesto a 75 rpm. O perfil de dissolução obtido é discriminativo e apresenta ótima precisão e exatidão. O estudo de estresse do fluconazol frente à degradação ácida, alcalina, oxidativa, térmica, fotolítica e em câmara climática (40 ºC/75%) mostrou a oxidação como fator importante, sendo a única condição a apresentar produto de degradação. O decaimento do teor do fármaco em amostras sob estudo de estabilidade conduzido em estufa, câmara climática e luz-UVC, foi determinado por CLAE e por ensaio microbiológico. Os resultados foram muito discrepantes, em que o teor da substância ativa se manteve acima de 90%, mas sua atividade apresentou decaimento significativo... / The antifungal agent fluconazole is a synthetic drug, developed in the 1980s, and first joined the class of triazoles. This study aimed to develop selective analytical methods and stability indicated method for fluconazole in capsules, including physical-chemical, microbiological, dissolution and stability studies. The methods of quantitative analysis employed and validated were: (i) first order derivative spectrophotometry in the UV at 268 nm in the concentration range of 150 - 350μg/mL. The average level found in the capsules was 96.42% (ii ) HPLC, C18 column and mobile phase consisting of methanol: water (60:40, V / V), the mean level obtained was 97.35%, (iii) determining the potency microbiological diffusion method in agar cylinders plate, using strains of Candida albicans ATCC 90028, where the average activity of fluconazole capsules was 88.96%. All these methods were validated and showed good selectivity, precision and accuracy. The HPLC method is able to separate the drug from its degradation product. The dissolution test was developed and validated using 900 mL of 0.1 M HCl as dissolution medium and basket at 75 rpm. The dissolution profile obtained is discriminatory and it has highly precise and accurate. The stress study of fluconazole against the degradation acid, alkaline, oxidative, thermal, photolytic and climate chamber (40 ° C/75%) showed the oxidation as an important factor, being the only condition to show a degradation product. The decrease of the drug in samples submitted to preliminary stability (conducted in stove, climate chamber and UVC-light) was determined by HPLC and microbiological assay. The results were very inconsistent in which the concentration of the drug remained above 90% but its activity had significant decrease showing approximately 30% activity. Fluconazole is an unstable drug and changes in its molecule lead to increased absorption of UV radiation... (Complete abstract click electronic access below)

A estabilidade é um importante parâmetro para avaliar a qualidade, segurança e eficácia exigidas para o registro sanitário de produtos farmacêuticos. A determinação deste parâmetro fundamenta-se não apenas no cumprimento de exigências legais, mas, também, na preocupação com a saúde pública, uma vez que a instabilidade pode estar relacionada à perda do efeito terapêutico ou à exposição do consumidor aos efeitos tóxicos de produtos de degradação. Vários países publicaram diretrizes para a avaliação da estabilidade farmacêutica. No Brasil, os estudos de estabilidade devem ser conduzidos segundo a Guia para Realização de Estudos de Estabilidade, publicada na Resolução-RE n.° 01, de 29 de julho de 2005. No presente trabalho, esta Guia foi avaliada nos aspectos considerados essenciais para obtenção de dados válidos sobre estabilidade. As condições de temperatura e umidade relativa predominantes no Brasil foram determinadas a fim de validar a condição de armazenamento definida na Guia, 30 °C ± 2 °C e 75 % ± 5 % de UR, para a condução do estudo de estabilidade de longa duração. Os resultados obtidos demonstram que a temperatura de 30 °C é adequada para a determinação da estabilidade de produtos farmacêuticos, entretanto, a umidade relativa, fixada em 75 %, não cobre todas as capitais brasileiras. Foi observado, com base na revisão bibliográfica, que existem algumas diferenças entre a Guia e as diretrizes estudadas e que a Guia apresenta alguns aspectos insuficientes que podem influenciar a determinação da estabilidade e do prazo de validade dos medicamentos objetos de registro na ANVISA. Estes aspectos foram discutidos criticamente e sugestões foram propostas a fim de subsidiar futuras alterações da Guia para Realização de Estudos de Estabilidade. / The stability is an important parameter to evaluate the demanded quality, security and effectiveness for the sanitary register of pharmaceutical products. The evaluation of this parameter is based not only on the fulfilment of legal requirements but also in the concern with the public health, once the instability can be related to the loss of the therapeutical effect or to the exposition of the consumer to the toxic effects of degradation products. Several countries had published guidelines for the evaluation of the pharmaceutical stability. In Brazil, the stability studies must be lead according to Guide for Accomplishment of Stability Studies, published in Resolução-RE n.º 01, of July 29th 2005. In the present work, this Guide had been evaluated in the aspects considered essential for attainment of the stability valid data. The temperature and predominant relative humidity conditions in Brazil had been determined in order to validate the storage condition defined in the Guide (30 °C ± 2 °C e 75 % ± 5 % de UR) for the conduction of the long term stability study. The obtained results demonstrate that 30 ºC is the adjusted temperature for the determination of the stability of pharmaceutical products, however, 75 % of UR, have not covered all the Brazilian capitals. It was observed, on the basis of the bibliographical revision, that there are some differences between the Guide and the guidelines studied, and the Guide presents some insufficient aspects that can influence the determination of the stability and the expiration date of drugs products objects of register in the ANVISA. These aspects had been argued critically and suggestions had been proposed in order to subsidize future alterations of the Guide for Accomplishment of Stability Studies.

A estabilidade é um importante parâmetro para avaliar a qualidade, segurança e eficácia exigidas para o registro sanitário de produtos farmacêuticos. A determinação deste parâmetro fundamenta-se não apenas no cumprimento de exigências legais, mas, também, na preocupação com a saúde pública, uma vez que a instabilidade pode estar relacionada à perda do efeito terapêutico ou à exposição do consumidor aos efeitos tóxicos de produtos de degradação. Vários países publicaram diretrizes para a avaliação da estabilidade farmacêutica. No Brasil, os estudos de estabilidade devem ser conduzidos segundo a Guia para Realização de Estudos de Estabilidade, publicada na Resolução-RE n.° 01, de 29 de julho de 2005. No presente trabalho, esta Guia foi avaliada nos aspectos considerados essenciais para obtenção de dados válidos sobre estabilidade. As condições de temperatura e umidade relativa predominantes no Brasil foram determinadas a fim de validar a condição de armazenamento definida na Guia, 30 °C ± 2 °C e 75 % ± 5 % de UR, para a condução do estudo de estabilidade de longa duração. Os resultados obtidos demonstram que a temperatura de 30 °C é adequada para a determinação da estabilidade de produtos farmacêuticos, entretanto, a umidade relativa, fixada em 75 %, não cobre todas as capitais brasileiras. Foi observado, com base na revisão bibliográfica, que existem algumas diferenças entre a Guia e as diretrizes estudadas e que a Guia apresenta alguns aspectos insuficientes que podem influenciar a determinação da estabilidade e do prazo de validade dos medicamentos objetos de registro na ANVISA. Estes aspectos foram discutidos criticamente e sugestões foram propostas a fim de subsidiar futuras alterações da Guia para Realização de Estudos de Estabilidade. / The stability is an important parameter to evaluate the demanded quality, security and effectiveness for the sanitary register of pharmaceutical products. The evaluation of this parameter is based not only on the fulfilment of legal requirements but also in the concern with the public health, once the instability can be related to the loss of the therapeutical effect or to the exposition of the consumer to the toxic effects of degradation products. Several countries had published guidelines for the evaluation of the pharmaceutical stability. In Brazil, the stability studies must be lead according to Guide for Accomplishment of Stability Studies, published in Resolução-RE n.º 01, of July 29th 2005. In the present work, this Guide had been evaluated in the aspects considered essential for attainment of the stability valid data. The temperature and predominant relative humidity conditions in Brazil had been determined in order to validate the storage condition defined in the Guide (30 °C ± 2 °C e 75 % ± 5 % de UR) for the conduction of the long term stability study. The obtained results demonstrate that 30 ºC is the adjusted temperature for the determination of the stability of pharmaceutical products, however, 75 % of UR, have not covered all the Brazilian capitals. It was observed, on the basis of the bibliographical revision, that there are some differences between the Guide and the guidelines studied, and the Guide presents some insufficient aspects that can influence the determination of the stability and the expiration date of drugs products objects of register in the ANVISA. These aspects had been argued critically and suggestions had been proposed in order to subsidize future alterations of the Guide for Accomplishment of Stability Studies.