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Validação de métodos para análise e estudos de estabilidade de anti-retrovirais em preparações farmacêuticas / Validation of analytical methods for analysis and stability studies of anti-retrovirais in pharmaceutical preparations.Taborianski, Andréia Montoro 11 August 2003 (has links)
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 organisms 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.
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Validação de métodos para análise e estudos de estabilidade de anti-retrovirais em preparações farmacêuticas / Validation of analytical methods for analysis and stability studies of anti-retrovirais in pharmaceutical preparations.Andréia Montoro Taborianski 11 August 2003 (has links)
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 organisms 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.
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Preparation and characterisation of pheroid vesicles / Charlene Ethel UysUys, Charlene Ethel January 2006 (has links)
Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.
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Preparation and characterisation of pheroid vesicles / Charlene Ethel UysUys, Charlene Ethel January 2006 (has links)
Pheroid is a patented system comprising of a unique submicron emulsion type
formulation. Pheroid vesicles consist mainly of plant and essential fatty acids and
can entrap, transport and deliver pharmacologically active compounds and other
useful molecules. The aim of this study was to show that a modulation of
components and parameters is necessary to obtain the optimum formula to be used
in pharmaceutical preparations.
Non-optimal or non-predictable stability properties of emulsions can be limiting for the
applications of emulsions (Bjerregaard et al., 2001:23). Careful consideration was
given to the apparatus used during the processing along with the ratios of the various
components added to the formulation and the storage conditions of the Pheroid
vesicles.
A preliminary study was performed to optimize the most accurate processing
parameters during emulsification. The effect of emulsification rate and time, the
temperature of the aqueous phase, the number of days the water phase were
gassed, the concentration of the surfactant, cremophor® RH 40, used and the
concentration of Vitamin F Ethyl Ester CLR added to the oil phase of the o/w
emulsion has been studied. Quantification of the mean particle size, zeta potential,
turbidity, pH and current values were used to characterize the emulsions. The
samples were characterised after 1, 2, 3, 7, 14, 21 and 28 days of storage. The
emulsions were also characterised with confocal laser scanning microscopy (CLSM)
to measure the number and size and size distribution of the vesicles.
After determination of the processing variables influencing the emulsion stability an
accelerated stability test was conducted on a final formula. In the present study,
accelerated stability testing employing elevated temperatures and relative humidity
were used with good accuracy to predict long-term stability of an o/w emulsion kept
at both 5 and 25 OC with 60 % relative humidity and 40 OC with 75 % relative
humidity. The results of the stability tests were presented in histograms of the
physical properties 24 hours, 1 month, 2 months and 3 months after preparation of
the emulsion.
It was concluded that Pheroid vesicles demonstrate much potential as a drug delivery
system. The high stability of this formula allows its use in a wide variety of
applications in the pharmaceutical industry. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.
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Preparation and characterisation of pheroid vesicles / Charlene Ethel UysUys, Charlene Ethel January 2006 (has links)
Pheroid is a patented system comprising of a unique submicron emulsion type
formulation. Pheroid vesicles consist mainly of plant and essential fatty acids and
can entrap, transport and deliver pharmacologically active compounds and other
useful molecules. The aim of this study was to show that a modulation of
components and parameters is necessary to obtain the optimum formula to be used
in pharmaceutical preparations.
Non-optimal or non-predictable stability properties of emulsions can be limiting for the
applications of emulsions (Bjerregaard et al., 2001:23). Careful consideration was
given to the apparatus used during the processing along with the ratios of the various
components added to the formulation and the storage conditions of the Pheroid
vesicles.
A preliminary study was performed to optimize the most accurate processing
parameters during emulsification. The effect of emulsification rate and time, the
temperature of the aqueous phase, the number of days the water phase were
gassed, the concentration of the surfactant, cremophor® RH 40, used and the
concentration of Vitamin F Ethyl Ester CLR added to the oil phase of the o/w
emulsion has been studied. Quantification of the mean particle size, zeta potential,
turbidity, pH and current values were used to characterize the emulsions. The
samples were characterised after 1, 2, 3, 7, 14, 21 and 28 days of storage. The
emulsions were also characterised with confocal laser scanning microscopy (CLSM)
to measure the number and size and size distribution of the vesicles.
After determination of the processing variables influencing the emulsion stability an
accelerated stability test was conducted on a final formula. In the present study,
accelerated stability testing employing elevated temperatures and relative humidity
were used with good accuracy to predict long-term stability of an o/w emulsion kept
at both 5 and 25 OC with 60 % relative humidity and 40 OC with 75 % relative
humidity. The results of the stability tests were presented in histograms of the
physical properties 24 hours, 1 month, 2 months and 3 months after preparation of
the emulsion.
It was concluded that Pheroid vesicles demonstrate much potential as a drug delivery
system. The high stability of this formula allows its use in a wide variety of
applications in the pharmaceutical industry. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2007.
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Solid-state Stability of Antibody-drug ConjugatesEunbi Cho (11192397) 28 July 2021 (has links)
<p>Antibody-drug conjugates (ADCs) combine
the cytotoxicity of traditional chemotherapy with the site-specificity of
antibodies by conjugating payloads to antibodies with immunoaffinity. However,
the conjugation alters the physicochemical properties of antibodies, increasing
the risks of various types of degradation. The effects of common risk factors
such as pH, temperature, and light on the stability of ADCs differ from their
effects on monoclonal antibodies (mAb) due to these altered physicochemical
properties. </p>
<p>To date, ADC researchers have
developed linkers with improved <i>in vivo</i> stability, and begun to
understand the deconjugation mechanisms <i>in vivo</i>. In contrast, the <i>in
vitro</i> stability of ADCs has not gained comparable attention. All nine of
the U.S. FDA approved ADCs are lyophilized to minimize the potential for
degradation. However, there are few studies on the solid-state stability of
ADCs. To evaluate lyophilized solids, pharmaceutical development relies heavily
on accelerated stability studies, which take months to determine the best formulation.
Characterization methods that are often used orthogonally with accelerated
studies include Fourier-transform infrared spectroscopy (FT-IR), Raman
spectroscopy, near-infrared spectroscopy (NIR), differential scanning
calorimetry (DSC), and x-ray powder diffraction (XRPD). Results from these methods are often poorly
correlated with stability, however. Thus, stability evaluation of solid-state ADC
products, and other recombinant protein drugs, is often a bottleneck in their
development.</p>
<p>To provide knowledge on how to
improve the <i>in vitro</i> stability of lyophilized ADC formulations, the solid-state
stability of ADC formulations with varying risk factors was studied in this
dissertation project. The first study investigated interactions between an ADC
and excipients in terms of solid-state stability enhancement. The second study
investigated the process-driven instability of ADCs during lyophilization using
various concentrations of ADCs. The first two studies incorporate a new method
called solid-state hydrogen/deuterium exchange coupled with mass spectrometry
(ssHDX-MS) as an analytical predictor of solid-state stability. The last study
investigated the effects of pH on the stability of labile hydrazones, as a
model for common linker chemistry used in ADCs. </p>
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Automatización del pronóstico y seguimiento de la vida útil de los productos fabricados en un laboratorio del sector farmacéutico usando Web API REST y modelos estadísticos / Automation of the forecasting and tracking of the shelf life of products manufactured in a pharmaceutical laboratory using Web API REST and statistical modelsNizama Huamanzana, Cesar Eduardo, Tapia Suaña, Juan Pablo 14 December 2021 (has links)
En la industria farmacéutica los estudios de estabilidad son de vital importancia, pues asegura la eficacia y calidad del producto que ofrece a la población. Todos los productos farmacéuticos deben tener un período de investigación con el fin de determinar su vida útil.
La presente propuesta de tesis está enfocada en el proceso de estudio de estabilidad, cuyo problema central se encuentran en las actividades manuales de la planificación y monitoreo del estudio, la deficiencia de lo descrito afecta el rendimiento del proceso y genera incertidumbre en la toma de decisiones estratégicas.
En consecuencia, la propuesta de solución se justifica en el diseño de una arquitectura tecnológica enfocada en la automatización del pronóstico y seguimiento de la vida útil de los productos fabricados en un laboratorio del sector farmacéutico, usando Web API REST y modelos estadísticos, permitiendo el monitoreo y control eficiente del proceso. Para lograr el éxito del proyecto, se ha analizado al objeto de estudio, identificando el problema principal. En la gestión del proyecto hacemos uso de los diversos artefactos y las buenas prácticas justificadas en la Guía del PMBOK®️.
Durante el diseño de la arquitectura empresarial se hizo uso del marco de trabajo Zachman con la metodología de arquitectura TOGAF. Asimismo, se presenta el modelado del proceso referente a la situación actual (AS-IS) usando la notación BPMN.
Finalmente, se identifican los componentes tecnológicos de la arquitectura del software utilizando conceptos de ingeniería, tácticas de diseño y representando la arquitectura del software desde un alto nivel a un nivel detallado con el uso del Modelo C4. / In the pharmaceutical industry, stability studies are of vital importance, as it ensures the efficacy and quality of the product that it offers to the population. All pharmaceutical products must have an investigation period in order to determine their shelf life.
This thesis proposal is focused on the stability study process, whose central problem lies in the manual activities of planning and tracking of the study, the deficiency of what is described affects the performance of the process and generates uncertainty in decision-making strategic.
Consequently, the solution proposal is justified in the design of a technological architecture focused on the automation of forecasting and monitoring of the shelf life of products manufactured in a laboratory of the pharmaceutical sector, using Web API REST and statistical models, allowing the monitoring and an efficient process control.
To achieve the project success, the object of study has been analyzed, identifying the main problem. In the project management, we make use of the various artifacts and good practices justified in the PMBOK®️ Guide.
During the design of the enterprise architecture, we used the Zachman framework with the TOGAF architecture methodology. In addition, the modeling of the process referring to the current situation (AS-IS) is presented using the BPMN notation.
Finally, the technological components of the software architecture are identified using engineering concepts, design tactics and representing the software architecture from a high level to a detailed level with the use of the C4 Model. / Tesis
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