Submitted by Pedro Barros (pedro.silvabarros@ufpe.br) on 2018-09-13T22:13:19Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Camila Maria Barros da Silva.pdf: 3423150 bytes, checksum: 4c1ae60d5368ec7f7f8f1a85c6100e86 (MD5) / Approved for entry into archive by Alice Araujo (alice.caraujo@ufpe.br) on 2018-09-18T15:07:44Z (GMT) No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Camila Maria Barros da Silva.pdf: 3423150 bytes, checksum: 4c1ae60d5368ec7f7f8f1a85c6100e86 (MD5) / Made available in DSpace on 2018-09-18T15:07:45Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Camila Maria Barros da Silva.pdf: 3423150 bytes, checksum: 4c1ae60d5368ec7f7f8f1a85c6100e86 (MD5) Previous issue date: 2017-07-28 / CAPES / O cloridrato de pilocarpina tem sido utilizado no tratamento da xerostomia, entretanto sua atuação sistêmica promove reações adversas indesejáveis. Tal problemática leva a necessidade da criação de formulações para a aplicação na mucosa bucal visando efeito local e diminuição da intensidade dos efeitos adversos. Assim, este trabalho objetivou o desenvolvimento de formulações termossensíveis utilizando Poloxamer 407 associado a polímeros naturais mucoadesivos para o carreamento do cloridrato de pilocarpina. Inicialmente foi realizada a caracterização das matérias primas por infravermelho (IV) e análise térmica. As formulações foram obtidas pela solubilização inicial dos polímeros naturais goma do cajueiro e goma karaya em água purificada e quitosana em solução de ácido acético a 1%. As concentrações utilizadas dos polímeros naturais foram de 0,25%, 0,5% e 1,0 % na proporção peso/volume (p/v). Posteriormente, o Poloxamer 407 foi adicionado à solução anterior na concentração de 18% (p/v) e mantida sob resfriamento (4°a 8°C) até completa solubilização do polímero. As formulações obtidas foram avaliadas quanto capacidade de transição solução-gel (sol-gel), temperatura e tempo de gelificação, viscosidade, módulo elástico e propriedades reológicas, além do perfil de liberação. As formulações de Poloxamer 407 18% contendo quitosana e goma do cajueiro em todas as concentrações não apresentaram propriedades de gelificação com o aumento de temperatura. Já as associadas a goma karaya apresentaram um incremento nas propriedades de gelificação com aumento da viscosidade. A formulação contendo goma karaya 1% apresentou maior viscosidade, menor tempo de transição sol-gel, assim como a maior capacidade mucoadesiva. Para avaliação do perfil de liberação, foram comparados o fármaco isolado, a formulação de Poloxamer 407 18% com pilocarpina e Poloxamer 407 18% + goma karaya 1% com pilocarpina e observou-se que a formulação contendo goma karaya 1% apresentou a liberação mais sustentada do fármaco. Diante disto, a utilização de polímeros naturais podem aumentar a capacidade geleificante de componentes já existentes no mercado, sendo a goma karaya um material promissor para a obtenção de novos sistemas mucoadesivos de liberação local e modificada. / Pilocarpine chloride has been used on treatment of xerostomia, however its systemic action promotes undesirable adverse events. Due to this problem it is necessary create formulation to be applied directly on buccal mucosa to produce local effect and reduce the intensity of adverse effects. So, this work aimed the development of thermosensitive formulation using poloxamer 407 associated to mucoadhesive natural polymers as carrier of pilocarpine chloride. First the characterization of raw materials was realized by infrared (IV) and thermal analysis. Formulations were obtained by initial solubilization of natural polymers cashew and karaya gums in purified water and chitosan in 1% acetic acid solution. The concentrations of the natural polymers used were 0.25, 0.5 and 1.0% in proportion weight/volume (w/v). After, the poloxamer 407 was added to previous solution in concentration of 18% (w/v) and maintained under cooling (4 to 8°C) until complete polymer solubilization. The formulations obtained were evaluated as to solution-gel (sol-gel) transition capacity, gelling temperature and time, elastic modulus and rheological properties. The gels with thermosensitive property were submitted to mucoadhesive force and release profile by dialysis method evaluation.Poloxamer 407 formulation 18% containing chitosan and cashew gum in all different concentrations did not presented gelling properties with temperature of increase. However, the formulation associated to karaya gum showed a increase in gelling properties with high viscosity. The 1% karaya gum formulation presented higher viscosity, shorter time of sol-gel transition, as well as greater mucoadhesive capacity. To release profile evaluation were compared the isolated drug, 18% poloxamer 407 formulation with pilocarpine and poloxamer 407 18% + karaya gum 1% with pilocarpine, which was observed that formulation containing 1% karaya gum showed more sustained release of drug. On these, the use of natural polymers can increase the gelling capacity of components on the market and karaya gum showed as promissor material to obtaining of new mucoadhesive systems to modified and local release.

No description available.

La vía de administración oral de fármacos es la más utilizada para lograr efectos sistémicos. Aproximadamente el 90% de todos los fármacos utilizados para este fin son administrados por esa vía. La respuesta terapéutica de un fármaco depende normalmente de una concentración adecuada del mismo, la cual se debe alcanzar y mantener en el sitio de acción. Numerosos principios activos de interés fármacoterapéutico presentan baja biodisponibilidad oral, debido principalmente a su baja solubilidad acuosa, entre los cuales se encuentra el Meloxicam, un antiinflamatorio no esteroideo usado en el tratamiento de la osteoartritis y otras enfermedades articulares. Posee mejor tolerancia gástrica disminuyendo las reacciones adversas frente a otros antinflamatorios motivo por el cual se utiliza con mayor frecuencia en patologías crónicas. Para poder mejorar su biodisponibilidad oral, en esta tesis se planteó la utilización de Dispersiones Sólidas como una estrategia farmacotécnica para mejorar la velocidad de disolución del fármaco. En el capítulo I se realiza una introducción sobre la importancia de las propiedades de los fármacos frente a su biodisponibilidad oral. Se describen las características de las Dispersiones Sólidas, del Meloxicam y del Poloxamer 188 utilizado para su obtención. Se incluye una extensa revisión bibliográfica que respalda el trabajo. En el Capítulo II se presentan todos los materiales utilizados en las distintas etapas de desarrollo. Asimismo, se exponen las técnicas empleadas para caracterizar las muestras obtenidas y los métodos utilizados en su obtención. En el Capítulo III se detalla la obtención de las Dispersiones Sólidas por el método de fusión. Se presentan las caracterizaciones fisicoquímicas, farmacéuticas y fisicomecánicas de las mismas y su comparación con las Mezclas Físicas obtenidas de ambos componentes en iguales proporciones. A partir de los datos obtenidos se sacan las conclusiones. En el capítulo IV se detalla la obtención de las Dispersiones Sólidas por el método de Atomización que incluye una introducción bibliografía. Se explican los pasos seguidos para seleccionar las condiciones operativas óptimas para el método teniendo en cuenta las características de los compuestos utilizados. Se detallan las caracterizaciones fisicoquímicas y farmacéuticas comparando estos resultados con muestras obtenidas por el método de fusión. Además se describe la incorporación de las muestras obtenidas en la Forma Farmacéutica Cápsulas comparando los perfiles de disolución con otra del Mercado Farmacéutico. Por último se discuten los resultados obtenidos y se presentan las conclusiones correspondientes. En el Capítulo V a partir de las conclusiones parciales se presentan las conclusiones generales de esta tesis, junto a los principales aspectos a considerar en trabajos futuros. / Oral drug administration is the most frequently used method to attain systemic effects. Approximately 90% of all drugs are orally administered. The therapeutic response to a drug usually depends on its correct concentration, which must be achieved and maintained in the action site. Numerous active pharmaceutical ingredients (API) show low oral bioavailability mainly due to their low solubility in water, such as Meloxicam. Meloxicam is a non-steroid anti-inflammatory used in the treatments for osteoarthritis and other joint disorders. Meloxicam has a better gastric tolerance decreasing adverse reactions compared to other anti-inflammatory drugs, which is why it is more widely used for treating chronic pathologies. In order to improve its oral bioavailability, this thesis poses solid dispersions as a technological strategy to improve the drug’s dissolution rate. On chapter I there is an introduction about the importance of drug properties against its oral bioavailability. The features/characteristics of the various types of solid dispersions and the methods used to obtain them are described on this chapter as well. In addition, properties of Meloxicam and Poloxamer 188 (a polymer used in formulations) are presented. An extensive bibliographic review is included. On chapter II all the materials used during the various stages of development are presented. Additionally, the techniques applied to characterize the obtained samples as well as the obtention methods are described. Chapter III details the development of Meloxicam-Poloxamer solid dispersions through the fusion/solidification method. Their physicochemical, pharmaceutical and physicomechanical characterizations are presented and analyzed. In addition, a comparison with the corresponding physical mixtures is given. From the collected data it can be concluded that the increase of the drug’s rate dissolution from solid dispersions is due to the humectant effect of Poloxamer. Chapter IV describes the development of solid dispersions through spray drying and also includes a bibliographical review. The steps that were followed to select optimum operating conditions are explained, considering the specific features of the system Meloxicam-Poloxamer and the challenge of working at low temperatures without organic solvents. The physico-chemical and pharmaceutical characterizations are detailed, comparing these results to those of the samples obtained through the fusion method. In addition, the incorporation of the obtained solid dispersions under the pharmaceutical form “capsules” is described, contrasting the dissolution profiles against other capsule formulations available in the pharmaceutical market. Finally, the results are discussed. It is concluded that the solid dispersions obtained through spray drying enhance even more Meloxicam’s dissolution rate due to the carrier’s humectant effect and the decrease in particle size. The same behavior is observed for the formulations added in the prepared capsules. On chapter V and from the partial conclusions, general conclusions of this thesis are presented along with the main aspects to be considered in future works.

La biopharmacie s'intéresse au devenir du médicament au contact d'un épithélium. Cela conditionne la biodisponibilité du principe actif, rendant les études biopharmaceutiques indispensables au développement des médicaments. L'obtention de données biopharmaceutiques in vitro passe par l'utilisation de cellules de diffusion. La variabilité des résultats expérimentaux obtenus nous a conduits à développer un nouveau dispositif nommé VitroPharma, destiné à optimiser l'étude de la perméabilité épithéliale. Son originalité réside dans la possibilité d'employer les milieux récepteurs semi-solides en substitution des milieux liquides habituels.Ce travail propose une exploration des capacités de VitroPharma en vue de sa validation. Le dispositif est testé en modalités de dose (i) finie et (ii) infinie, sur (i) peau porcine et (ii) membrane artificielle de silicone, respectivement. Des milieux récepteurs (i) liquide, (ii) semi-solide (hydrogel d'agarose) et (iii) thermogélifiant (hydrogel de poloxamer) sont évalués. La caféine et la testostérone sont utilisées comme composés modèles. Les résultats sont comparés à une méthode de référence.De plus, deux problématiques expérimentales peu étudiées dans la littérature sont évaluées : (i) la formation de bulles à l'interface milieu récepteur-membrane et (ii) l'altération de l'hydratation des membranes biologiques en cours d'essai. Il ressort que l'utilisation de VitroPharma combinée à un milieu récepteur thermogélifiant permet (i) de limiter la formation de bulles et (ii) de contrôler le contenu en eau des explants cutanés.Ainsi le dispositif VitroPharma apparait comme adapté à la tenue d'essais de perméabilité épithéliale, apportant notamment, (i) une manipulation facilitée, (ii) une optimisation des conditions d'essai et (iii) l'obtention de résultats cinétiques de pénétration. Des exemples de développements cliniques mettant à profit les performances de VitroPharma sont présentés en conclusion / Biopharmacy studies the outcomes of contact between a medicine and its administration site epithelium, thus determining active compound bioavailability. Hence, biopharmaceutical studies are paramount to drug development processes. Biopharmaceutical data are obtained in vitro using experimental devices (i.e., diffusion cells) but show high variability. To overcome this limitation we development a new experimental device, called VitroPharma, meant to optimize the study of epithelial permeability. Distinctiveness of this innovating diffusion cell is due to substitution of classical liquid receptor medium with semi-solid medium.In this work, validation studies of VitroPharma are detailed including (i) finite and (ii) infinite dosing protocols using (i) biological membrane (i.e., pig ear skin) and (ii) artificial silicone membrane, respectively. Three different types of receptor medium are employed: (i) liquid medium, (ii) semi-solid medium (i.e., 2% agarose hydrogel) and (iii) thermogelifying medium (i.e., 20% poloxamer 407 hydrogel). Caffeine and testosterone are used as model compounds. Permeability results are displayed and compared to that obtained using reference Franz static diffusion cell.Furthermore, two experimental pitfalls often mentioned but scarcely studied in literature are evaluated, that is (i) bubble formation at the membrane-receptor medium interface and (ii) biological membrane hydration modification over assay time. VitroPharma combined to thermogelifying receptor medium was found efficient (i) in reducing bubble formation and (ii) enabling control of biological membrane water content.Therefore, VitroPharma appears adapted to the in vitro study of epithelial permeability, enabling (i) easy handling, (ii) optimized experimental parameters and (iii) dual penetration and permeation determination. To conclude this work, examples of clinical outcomes that could advantageously use VitroPharma are presented

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Orientadora: Daniele Ribeiro Araujo. / Dissertação (mestrado) - Universidade Federal do ABC. Programa de Pós-Graduação em Biossistemas.

Orientadora: Daniele Ribeiro Araujo. / Dissertação (mestrado) - Universidade Federal do ABC. Programa de Pós-Graduação em Biossistemas.

No description available.

No description available.

No description available.