Obtenção e caracterização de sistemas particulados de quitosana para liberação gástrica de amoxicilina

The infection caused by Helicobacter pylori (H. pylori) is associated with gastroduodenal inflammation can lead to the development of gastritis, gastric or duodenal ulcer and gastric cancer (type 1 carcinogen for stomach cancer). Amoxicillin is used as first-line therapy in the treatment of H. pylori associated to metronidazole or clarithromycin, and a proton pump inhibitor. However, the scheme is not fully effective due to inadequate accumulation of antibiotics in gastric tissue, inadequate efficacy of ecological niche of H. pylori, and other factors. In this context, this study aimed to obtaining and characterization of particulate systems gastrorretentivos chitosan - amoxicillin aiming its use for treatment of H. pylori infections. The particles were obtained by the coacervation method / precipitation using sodium sulfate as precipitating agent and crosslinking and two techniques: addition of amoxicillin during preparation in a single step and the sorption particles prior to amoxycillin prepared by coacervation / precipitation and spray drying. The physicochemical characterization of the particles was performed by SEM, FTIR, DSC, TG and XRD. The in vitro release profile of amoxycillin free and incorporated in the particles was obtained in 0.1 N HCl (pH = 1.2). The particles have higher encapsulation efficiency to 80% spherical shape with interconnected particles or adhered to each other, the nanometric diameter to the systems obtained by coacervation / precipitation and fine for the particles obtained by spray drying. The characterization by FTIR, DSC and XRD showed that the drug was incorporated into the nanoparticles dispersed in the polymeric matrix. Thermal analysis (TG and DSC) indicated that encapsulation provides greater heat stability to the drug. Amoxicillin encapsulated in nanoparticles had slower release compared to free drug. The particles showed release profile with a faster initial stage (burst effect) reaching a maximum at 30 minutes 35% of amoxicillin for the system in 1: 1 ratio relative to the polymer and 80% for the system in the ratio 2: 1. Although simple and provide high encapsulation efficiency of amoxicillin, the process of coacervation, precipitation in one step using sodium sulfate as precipitant / cross-linker must be optimized in order to adjust the release kinetics according to the intended application.

Desenvolvimento de Sistemas Microparticulados Superparamagnéticos Gastro-resistentes para Diagnóstico e Terapêutica

This work aimed to develop a suitable magnetic system for administration by the oral route. In addition to that, it was intended to review the current uses of magnetic systems and the safety related to magnetic field exposure. Methods: Coprecipitation and emulsification/crosslinking were carried out in order to synthesize magnetite particles and to coat them, respectively. Results: According to literature review, it was found that magnetic particles present several properties such as magnetophoresis in magnetic field gradient, production of a surrounding magnetic field, and heat generation in alternated magnetic field. When the human organism is exposed to magnetic fields, several interaction mechanisms come into play. However, biological tissues present low magnetic susceptibility. As a result, the effects are not so remarkable. Concerning the development of a magnetic system for oral route, uncoated magnetite particles did undergo significant dissolution at gastric pH. On the other hand, such process was inhibited in the xylan-coated particles. Conclusions: Due to their different properties, magnetic systems have been widely used in biosciences. However, the consequent increased human exposure to magnetic fields has been considered relatively safe. Concerning the experimental work, it was developed a polymer-coated magnetic system. It may be very promising for administration by the oral route for therapy and diagnostic applications as dissolution at gastric pH hardly took place

Biodistribuição do pertecnetato de sódio após desvio gástrico em Y de Roux (técnica de capella)

O desvio gástrico em Y de Roux é a técnica cirúrgica mais utilizada no tratamento da obesidade mórbida. Esta operação reduz o volume do estômago e o comprimento do intestino delgado, gerando alterações estruturais e metabólicas que podem influenciar no resultado de exames cintilográficos de pacientes operados. Com o objetivo de avaliar a biodistribuição pós-operatória do pertecnetato de sódio (Na99mTc) em órgãos de ratos Wistar submetidos à técnica do bypass (desvio) gástrico em Y de Roux (BGYR), foram utilizados 12 ratos distribuídos aleatoriamente em grupo tratado (n=6), submetido à cirurgia do BGYR e o grupo controle (C; n=6). No 15º dia de pós-operatório foi administrado 0,1 mL via plexo orbital de Na99mTc aos animais dos dois grupos, com atividade radioativa média de 0,66MBq. Após 30 minutos, os ratos foram mortos e retirados fragmentos de tireóide, coração, pulmão, fígado, estômago, rim e fêmur. As amostras foram lavadas com solução salina 0,9%, pesadas e submetidas ao Contador Gama 1470, WizardTM Perkin-Elmer-Finlândia para determinação do percentual de atividade radioativa total por grama (%ATI/g) de cada órgão. Empregou-se o teste t de Student para análise estatística, considerando-se significantes as diferenças das médias quando p<0,05. Redução significante na média de %ATI/g foi observada no fígado, estômago e fêmur dos animais submetidos à cirurgia de BGYR comparada ao grupo controle (p<0,05). Nos demais órgãos não houve diferença estatisticamente significativa entre os grupos. Em conclusão, a cirurgia BGYR em ratos modificou a biodistribuição do Na99mTc em alguns órgãos, podendo ter implicações clínicas na interpretação de exames cintilográficos. Este estudo xi teve um caráter multidisciplinar com a participação de pesquisadores das áreas de Cirurgia Experimental, Farmácia, Radiobiologia, Medicina Nuclear e Estatística

Obtenção de sistemas multiparticulados de isoniazida revestidos com polímero de liberação entérica

Known for thousands of years, tuberculosis (TB) is the leading cause of mortality by a single infectious disease due to lack of patient adherence to available treatment regimens, the rising of multidrug resistant strains of TB (MDR-TB) and co-infection with HIV virus. Isoniazid and rifampicin are the most powerful bactericidal agents against M. tuberculosis. Because of that, this couple of drugs becomes unanimity in anti-TB treatment around the world. However, the rifampicin in acidic conditions in the stomach can be degraded rapidly, especially in the presence of isoniazid, which reduces the amount of available drug for absorption, as well as its bioavailability, contributing to the growing resistance to tuberculostatic drugs. Rifampicin is well absorbed in the stomach because of its high solubility between pH 1 and 2 and the gastric absorption of isoniazid is considered poor, therefore it is mostly intestinal. This work has as objective the development of gastro-resistant multiple-systems (granules and pellets) of isoniazid aiming to prevent the contact with rifampicin, with consequent degradation in acid stomach and modulate the release of isoniazid in the intestine. Granules of isoniazid were obtained by wet method using both alcoholic and aqueous solutions of PVP K-30 as aggregating and binder agent, at proportions of 5, 8 and 10%. The influence of the excipients (starch, cellulose or filler default) on the physical and technological properties of the granules was investigated. The pellets were produced by extrusionesferonization technique using isoniazid and microcrystalline cellulose MC 101 (at the proportion of 85:15) and aqueous solution of 1% Methocel as platelet. The pellets presented advantages over granular, such as: higher apparent density, smaller difference between apparent and compaction densities, smoother surface and, especially, smaller friability, and then were coated with an organic solution of Acrycoat L 100 ® in a fluidized bed. Different percentages of coating (15, 25 and 50%) were applied to the pellets which had their behavior evaluated in vitro by dissolution in acidic and basic medium. Rifampicin dissolution in the presence of uncoated and coated isoniazid pellets was evaluated too. The results indicate that the gastro resistance was only achieved with the greatest amount of coating and isoniazid is released successfully in basic step. The amount of rifampicin in the dissolution medium when the isoniazid pellets were not coated was lower than in the presence of enteric release pellets. Therefore, the polymer Acrycoat L 100 ® was efficient for coating with gastro-resistant function and can solve the problem of low bioavailability of rifampicin and help to reduce its dosage

Prevalência de incontinência urinária e fatores associados em idosos institucionalizados

Urinary incontinence (UI) is a geriatric syndrome that is especially prevalent in institutionalized individuals, and that causes economic and social impacts derived from treatment costs and overload of caregiver. UI also entails physical consequences to the health of the elderly, such as urinary tract infections or pressure ulcers, among other health problems. However, the existing national research on this condition is still scarce and comprises serious methodological biases. Therefore, the objective of this study is to determine the prevalence of urinary incontinence and associated factors in institutionalized elderly. A cross-sectional study is presented herein, conducted between October and December, 2013 and carried out in 10 nursing homes in the city of Natal (Northeast Brazil). UI was verified through the program Minimum Data Set version 3.0, which was also used to assess fecal incontinence, urinary devices and UI control programs. Data collection included sociodemographic information, UI characterization, as well as variables related to the institution itself and to health conditions (comorbidities, medication, pelvic floor surgery, Barthel Index for functional capacity and Pfeiffer test for cognitive status). Bivariate analysis was performed using the Chi-Square Test (or Fisher‟s Exact Test) and the Linear Chi-Square Test, calculating the prevalence ratio with 95% confidence interval. Variables with p value under 0.20 were included in the multivariate analysis, which was performed using the Stepwise Forward logistic regression. The inclusion of variables in the final model depended on the likelihood ratio test, absence of multicollinearity and on the Hosmer-Lemeshow test. A statistical significance level of 0.05 was considered. Six (1.8%) hospitalized elderly, one individual in palliative care (0.3%) and one (0.3%) individual under the age of 60 were excluded from the study. The final sample consisted of 321 elderly, mostly females, with a mean age of 81.5 years. The prevalence of UI was 59.43% and the final model revealed statistically a significant association between UI and white race, physical inactivity, stroke, mobility constraints and cognitive decline. The most frequent UI type was functional UI due to physical or cognitive disability, and incontinence control measures were applied only to a minority of residents (approximately 8%). It is concluded that UI is a health issue that affects more than half of the institutionalized elderly, and is associated with white race, physical inactivity, stroke and other geriatric syndromes such as immobility and cognitive disability. Most of these associated factors are modifiable and therefore the findings of this study highlight the importance of UI prevention and treatment in nursing homes, which include general measures, such as physical and psychosocial activities, and specific measures, such as prompted voiding

O desempenho da compartimentação horizontal seletiva na promoção da segurança contra incêndio em edificações

The thesis presents the results of research that addresses the performance of selective horizontal partitioning to promote Fire Safety in Buildings - FSB. Horizontal partitioning is a passive protection measure, settable in the early stages of the design process and controlled by the architect. However, there is a frequent reconfiguration of the rooms in academic buildings to adjust them for the space demand. Thus, large classrooms could turn into two or more smaller rooms, for example. Regardless when the subdivision occurs in the design phase or during the occupation of the building, the regulations just ensures the compartimentation of the room if all fireguard devices are present in the room. Knowing the fire's first minutes are the most important for life protection, we defend the hypothesis that a kind of partitioning ignored by regulatory standards is able to favoring the building vacancy and occupants rescue, for promote the room’s smoke exhaust. The performance of the selective horizontal partitioning due different blend of openings for smoke outlet was simulated on CFD software. The results indicate that selective horizontal partitioning is able to promote an upper smoke free layer and delay the indoor temperature growth.

O desempenho da compartimentação horizontal seletiva na promoção da segurança contra incêndio em edificações

The thesis presents the results of research that addresses the performance of selective horizontal partitioning to promote Fire Safety in Buildings - FSB. Horizontal partitioning is a passive protection measure, settable in the early stages of the design process and controlled by the architect. However, there is a frequent reconfiguration of the rooms in academic buildings to adjust them for the space demand. Thus, large classrooms could turn into two or more smaller rooms, for example. Regardless when the subdivision occurs in the design phase or during the occupation of the building, the regulations just ensures the compartimentation of the room if all fireguard devices are present in the room. Knowing the fire's first minutes are the most important for life protection, we defend the hypothesis that a kind of partitioning ignored by regulatory standards is able to favoring the building vacancy and occupants rescue, for promote the room’s smoke exhaust. The performance of the selective horizontal partitioning due different blend of openings for smoke outlet was simulated on CFD software. The results indicate that selective horizontal partitioning is able to promote an upper smoke free layer and delay the indoor temperature growth.