• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 27
  • 3
  • 1
  • 1
  • Tagged with
  • 34
  • 34
  • 22
  • 20
  • 20
  • 20
  • 18
  • 18
  • 17
  • 17
  • 16
  • 16
  • 12
  • 12
  • 9
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Mianserina : desenvolvimento e validação de métodos analíticos e estudo da estabilidade

Sfair, Letícia Lenz January 2012 (has links)
O cloridrato de mianserina é um fármaco utilizado no tratamento da depressão e depressão associada a ansiedade. Seu efeito antidepressivo é atribuído, principalmente, ao bloqueio dos receptores 2-adrenérgicos pré-sinápticos e à atividade antagonista nos receptores de serotonina. A mianserina é classificada como um antidepressivo atípico, tendo como base o seu mecanismo de ação nãodefinido. A análise de fármacos é fundamental nas diversas fases do desenvolvimento farmacêutico e a literatura pesquisada apresenta poucos relatos de determinação quantitativa e estudos de estabilidade deste fármaco na forma farmacêutica comprimido revestido. Assim, objetivou-se o desenvolvimento e validação de métodos analíticos para determinação qualitativa e quantitativa por espectrofotometria na região do ultravioleta (UV), cromatografia líquida de alta eficiência (CLAE) e eletroforese capilar (EC). Inicialmente foi realizada a caracterização da substância química de referência (SQR) de cloridrato de mianserina por espectroscopia de absorção na região do infravermelho (IV), análise térmica por calorimetria exploratória de varredura (DSC), determinação da faixa de fusão, espectrometria de massas e ressonância magnética nuclear. Além disso, o trabalho apresenta o ensaio de dissolução e o estudo da estabilidade do fármaco nos comprimidos revestidos com isolamento e identificação do produto de degradação majoritário obtido em condições oxidativas. A identificação do produto de degradação majoritário foi realizada por cromatografia líquida de ultraperformance (UPLC) acoplado à espectrometria de massas (EM). / Mianserin hydrochloride is a drug for the treatment of depressive illness and depression associated with anxiety. Its antidepressant effect is mainly attributed to presynaptic alfa-2-adrenoreceptor blocking activity and serotonin receptors antagonism. Mianserin is classified as an atypical antidepressant, based on its mechanism of action not defined. The drug analysis is necessary in all steps of the pharmaceutical development and the literature has few reports of quantitative determination and stability studies of this drug in pharmaceutical formulation. Thus, the objective was the development and validation of analytical methods for qualitative and quantitative determination by UV spectrophotometry, liquid chromatography (LC) and capillary electrophoresis (CE). Initially was performed the characterization of mianserin reference standard by infrared spectroscopy (IV), thermal analysis by differential scanning calorimetry (DSC), determination of melting range, by mass spectrometry (MS) and by nuclear magnetic resonance techniques. Besides, it presents a dissolution test and stability study of the drug in coated tablets by the isolation and identification of the major degradation product from oxidative conditions. The identification of the major degradation product was performed by ultra high performance liquid chromatography (UPLC) coupled to tandem mass spectrometry (MS).
32

Desenvolvimento de metodologia para análise de ceftiofur sódico e estudo da estabilidade / Development of methodology for ceftiofur sodium analysis and stability study

Souza, Marinês Jost e January 2008 (has links)
Este trabalho objetivou o desenvolvimento e validação de métodos analíticos para determinação de ceftiofur pó para solução injetável e o estudo da fotoestabilidade do fármaco. Os métodos por cromatografia em camada delgada, cromatografia líquida de alta eficiência (CLAE), espectrofotometria no ultravioleta (UV) foram utilizados para análise qualitativa do fármaco na forma farmacêutica. A determinação quantitativa foi realizada através dos métodos cromatografia líquida de alta eficiência, espectrofotometria no ultravioleta e ensaio microbiológico método de difusão em ágar - cillindros em placas, delineamento 3x3, avaliando-se os parâmetros descritos pelas guias de validação. Os resultados obtidos através destes métodos foram comparados estatisticamente por ANOVA, que indicou não haver diferenças estatisticamente significativas entre os mesmos. Estudo preliminar da estabilidade do ceftiofur frente a degradação alcalina, ácida, oxidativa e fotolítica mostrou a oxidação, a temperatura, a luz e a condição alcalina como fatores importantes da degradação. O fármaco é instável às radiações UV-C, em maior grau, e UV-A (degradação menos intensa), em solução. A cinética de fotodegradação do ceftiofur sódico em solução aquosa demonstrou cinética de primeira ordem de reação. / The aim of this study was the development and validation of analytical methods to the determination of ceftiofur sodium in powder for injectable preparation and the photostability study of the drug after reconstitution of the pharmaceutical dosage form with injectable water. Thin-layer chromatography (TLC), high performance liquid chromatography (HPLC) and ultraviolet spectrophotometry (UV), methods were employed to the qualitative analysis of the drug in pharmaceutical formulation. The quantitative determination was performed through the validation of HPLC, UV spectrophotometry and microbiological assay 3x3 using the cylinder plate, evaluating the guidances validation parameters. The results obtained by three methods were compared by ANOVA, which indicated that they are equivalent. Preliminary study of ceftiofur through alkaline, acid, oxidative and fotolitic degradation shows sensibility to oxidation, light and alkaline medium. The drug is unstable to UV-C and UV-A radiations, both in solution, being the degradation on UV-C more intense. The photodegradation kinetics of ceftiofur sodium solutions show first-order kinetic of reaction.
33

Solid-state Stability of Antibody-drug Conjugates

Eunbi 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>
34

Développement et évaluation de la stabilité de formulations pharmaceutiques destinées à la population pédiatrique

Coache, Daphné 03 1900 (has links)
Le manque de produits pharmaceutiques destinés à la population pédiatrique est un problème auquel sont confrontés les professionnels de la santé. Les pharmaciens doivent fréquemment se tourner vers les médicaments destinés aux adultes afin de fournir aux jeunes patients les traitements adéquats. L’utilisation de préparations magistrales pour adapter les médicaments homologués aux besoins de la population pédiatrique reste, encore à ce jour, l’option la plus souvent utilisée. Dans ce mémoire, nous proposons le développement et l’évaluation de nouvelles formulations pharmaceutiques destinées à la population pédiatrique afin de bonifier les options thérapeutiques mises à la disposition des professionnels de la santé. De plus, nous avons exploré l’utilisation de nouvelles techniques spécialisées pour surmonter des défis analytiques rencontrés, ultimement dans le but de déterminer en toute confiance la stabilité et la sécurité de ces nouvelles formulations. La première étude visait à évaluer la stabilité de préparations magistrales de chlorhydrate de clonidine (20 µg/mL) préparées avec des comprimés dans le véhicule commercial Ora-Blend. Les formulations embouteillées ont été conservées à 25°C/60% RH pendant 90 jours. Les défis analytiques rencontrés lors de l’analyse de la stabilité chimique ont été surmontés par l’implémentation d'une nouvelle méthode d'extraction en phase solide, ayant permis d’optimiser la quantification du chlorhydrate de clonidine, se retrouvant qu’en très faible quantité dans les formulations orales. L'absence d'instabilités physiques, évaluée par des mesures qualitatives et quantitatives, et l’absence d'instabilités chimiques, mise en évidence par une méthode HPLC-UV indicatrice de stabilité, confirment qu’accorder une date de péremption de 90 jours à ces préparations magistrales serait approprié. La deuxième étude portait sur l’évaluation de la stabilité de préparations magistrales d’hydroxyurée (100 mg/mL) dans l’Ora-Blend. Dans le cadre de cette étude, différentes méthodes de préparation (mortier, mélangeur, QuartetRx) et différentes sources de principe actifs (poudre, contenu des capsules, capsules entières) ont été étudiées. Toutes les formulations ont été conservées à 25°C pendant 90 jours dans des bouteilles et 14 jours dans des seringues orales. Le développement d'une méthode HPLC indicatrice de stabilité impliquant la dérivation de l’hydroxyurée par le xanthydrol aura permis la rétention l’hydroxyurée sur une colonne à phase inverse de type C18. Plus de 90.0 % de la concentration initiale d’hydroxyurée a été conservé tout au long de l’étude, et ce, pour toutes les conditions testées. L’évaluation visuelle des préparations n’a révélé aucun changement au cours de l’étude de stabilité. Des changements de pH allant jusqu'à 1.6 unités ont toutefois été observés après 90 jours d’entreposage et ont mis en lumière une voie de dégradation de l’hydroxyurée, générant ultimement l’ion ammonium. Ce dernier a été quantifié et les concentrations mesurées, définies comme acceptables. Les résultats ont montré que toutes les formulations d’hydroxyurée étudiées sont demeurées stables jusqu’à 90 jours à 25°C. Pour terminer, une étude exploratoire ayant pour but d’évaluer des comprimés à croquer à saveur d’érable a été réalisée. Le sucre d’érable et un arôme naturel d’érable ont été ajoutés à la composition des comprimés afin d’obtenir une saveur suffisamment prononcée pour masquer le goût amer de l’acétaminophène. Une étude de stabilité préliminaire, impliquant une période de 30 jours d’entreposage dans des conditions de stabilité accélérées (40°C/75%RH), aura permis d’explorer les propriétés physico-chimiques de cette nouvelle formulation, de soulever les défis potentiels et de générer des hypothèses en lien avec l’augmentation de dureté observée après seulement 14 jours d’entreposage. Les résultats de cette étude préliminaire serviront de point de départ pour le futur développement de produits pharmaceutiques à la saveur du Québec. Les techniques utilisées et les études réalisées dans le cadre de ce projet de maîtrise auront permis de générer des résultats robustes qui pourront être utilisés par les professionnels de la santé. Ces informations seront pertinentes à la pratique pharmaceutique et permettront d’offrir à la population pédiatrique des nouvelles options de traitement sécuritaires et efficaces. / The lack of pharmaceuticals intended to the pediatric population is an issue facing healthcare professionals. Pharmacists must frequently resort to adult treatments to provide adequate treatment to young patients. The use of compounding to adapt commercial drugs to the needs of the pediatric population is still, to this day, the most considered option. In this master’s thesis, we propose the development and evaluation of new medicinal preparations for pediatrics in order to improve and diversify the therapeutic options available to healthcare professionals. In addition, we have explored the use of new specialized techniques to overcome analytical challenges encountered, with the goal of confidently determining the stability and safety of these new formulations. The first study aimed to assess the stability of compound preparations of clonidine hydrochloride (20 µg / mL) prepared with tablets in the commercial vehicle Ora-Blend. Bottled formulations were stored at 25°C/60% RH for 90 days. The analytical challenges encountered during the analysis of chemical stability were overcome by the implementation of a new method of solid phase extraction, which allowed to optimize the quantification of clonidine hydrochloride, present in very small amount in oral formulations. The absence of physical instabilities, assessed by qualitative and quantitative measurements, and the absence of chemical instabilities, as demonstrated by a stability indicating HPLC-UV method, confirm that it would be appropriate to grant a 90-day expiration date to these compounded oral liquids. The second study evaluated the stability of compound preparations of hydroxyurea (100 mg / mL) in Ora-Blend. In this study, different preparation methods (mortar, mixer, QuartetRx) and different sources of hydroxyurea (powder, content of capsules, whole capsules) were studied. All formulations were stored at 25°C for 90 days in bottles and 14 days in oral syringes. The development of a stability indicating HPLC method involving the derivatization of hydroxyurea by xanthydrol will have enabled hydroxyurea retention on a C18 type reverse phase column. Over 90.0% of the initial hydroxyurea concentration was recovered throughout the study under all conditions tested. Visual evaluation of the preparations did not reveal any changes during the stability study. Changes in pH of up to 1.6 units were observed after 90 days of storage and revealed a degradation pathway for hydroxyurea, ultimately generating ammonium ion. The latter was quantified, and the measured concentrations defined as acceptable. The results showed that all hydroxyurea formulations studied were stable for up to 90 days at 25°C. Finally, an exploratory study to evaluate maple flavored chewable tablets was carried out. Maple sugar and a natural maple flavor have been added to the composition of the tablets to achieve a flavor strong enough to mask the bitter taste of acetaminophen. The pre-stability study, involving a period of 30 days of storage under accelerated stability conditions (40°C/75% RH), will have made it possible to explore the physicochemical properties of this new formulation, to raise the potential challenges and generate hypotheses related to the increase in hardness observed after only 14 days of storage. The results of this preliminary study will serve as a starting point for the future development of pharmaceutical products with a Quebec flavor. The techniques used and the studies performed will have generated robust results that could help healthcare professionals in their practice.

Page generated in 0.077 seconds