Controle de qualidade físico-químico e biodisponibilidade relativa em ratos de suspensões orais de naproxeno sódico obtidas de farmácias de manipulação na cidade do Natal RN

Compounded medicines have been reported by the ANVISA due to decreased of the therapeutic response or toxicity of these formulations. The aim of this work was to investigate the physicochemical quality control among naproxen sodium oral suspensions 25 mg/mL obtained from six compounding pharmacies (A, B, C, D, E and F) and the manufactured suspension (R). In the quality control test, the tests of pH, content, homogeneity, volume and physical and organoleptic characteristics were performed according to the Brazilian Pharmacopoeia. The analytical method for determination of naproxen in suspensions was validate. This method showed excellent precision, accuracy, linearity and specificity. In the content test the suspensions B, C and E showed lower value and the F suspension showed a high value of the content. The products C and E were disapproved in the description of the physical and organoleptic characteristics test. In the pH test, three suspensions were outside specifications (C, E and F). Only the products R, A and D showed satisfactory results in these tests and therefore they were approved for relative bioavailability test. The R, A and D suspensions were orally administered to Wistar rats and the blood samples were taken at time intervals of 10, 20, 40, 60 min, 3, 4, 6, 24 and 48 h. The plasma samples were immediately stored at 80 ºC until analysis of HPLC. The bioanalytical method validation showed specificity, linearity (R2 0.9987), precision, accuracy, good recovery and stability. The chromatographic conditions were: flow rate of 1.2 mL.min-1 with a mobile phase of acetonitrile : sodium phosphate buffer pH 4.0 (50:50, v/v) at 280 nm, using a C18 column. The confidence interval of 90% for the Cmax and AUCt ratio was within the range of 80 - 125% proposed by the FDA. Only one suspension, obtained from the compounding pharmacy D, was considered bioequivalent to the rate of absorption under the conditions proposed by this study. Thus, the results indicate the need for strict supervision from the relevant authorities to ensure the patient safety and the quality of compounded drugs by pharmacies

Produção e avaliação de nanoemulsão catiônica como possível vetor não-viral para pIRES2-EGFP

Gene therapy is based on the transfer of exogenous genetic material into cells or tissues in order to correct, supplement or silencing a particular gene. To achieve this goal, efficient vehicles, viral or non-viral, should be developed. The aim of this work was to produce and evaluate a nanoemulsion system as a possible carrier for no-viral gene therapy able to load a plasmid model (pIRES2-EGFP). The nanoemulsion was produced by the sonication method, after been choose in a pseudo-ternary phase diagram build with 5 % of Captex 355®, 1.2 % of Tween 80®, 0.8 % of Span 80®, 0.16% of stearylamine and water (to 100 %). Measurements of droplet size, polydispersity index (PI), zeta potential, pH and conductivity, were performed to characterize the system. Results showed droplets smaller than 200 nm (PI < 0.2) and zeta potential > 30 mV. The formulation pH was near to 7.0 and conductivity was that expected to oil in water systems (70 to 90 μS/s) A scale up study, the stability of the system and the best sterilization method were also evaluated. We found that the system may be scaled up considering the time of sonication according to the volume produced, filtration was the best sterilization process and nanoemulsions were stable by 180 days at 4 ºC. Once developed, the complexation efficiency of the plasmid (pDNA) by the system was tested by agarose gel electrophoresis retardation assay.. The complexation efficiency increases when stearylamine was incorporated into aqueous phase (from 46 to 115 ng/μL); regarding a contact period (nanoemulsion / pDNA) of at least 2 hours in an ice bath, for complete lipoplex formation. The nanoemulsion showed low toxicity in MRC-5 cells at the usual transfection concentration, 81.49 % of survival was found. So, it can be concluded that a nanoemulsion in which a plasmid model was loaded was achieved. However, further studies concerning transfectation efficiency should be performed to confirm the system as non-viral gene carrier

Preparação e carcterização de complexos multicomponentes contendo ciclodextrinas e benznidazol

The benznidazole (BNZ) is the only alternative for Chagas disease treatment in Brazil. This drug has low solubility, which restricts its dissolution rate. Thus, the present work aimed to study the BNZ interactions in binary systems with beta cyclodextrin (β-CD) and hydroxypropyl-beta cyclodextrin (HP-β-CD), in order to increase the apparent aqueous solubility of drug. The influence of seven hydrophilic polymers, triethanolamine (TEA) and 1-methyl-2- pyrrolidone (NMP) in benznidazole apparent aqueous solubility, as well as the formation of inclusion complexes was also investigated. The interactions in solution were predicted and investigated using phase solubility diagram methodology, nuclear magnetic resonance of protons (RMN) and molecular modeling. Complexes were obtained in solid phase by spray drying and physicochemical characterization included the UV-Vis spectrophotometric spectroscopy in the infrared region, scanning electron microscopy, X-ray diffraction and dissolution drug test from the different systems. The increment on apparent aqueous solubility of drug was achieved with a linear type (AL) in presence of both cyclodextrins at different pH values. The hydrophilic polymers and 1-methyl-2-pyrrolidone contributes to the formation of inclusion complexes, while the triethanolamine decreased the complex stability constant (Kc). The log-linear model applied for solubility diagrams revealed that both triethanolamine and 1-methyl-2-pyrrolidone showed an action cosolvent (both solvents) and complexing (1-methyl-2-pyrrolidone). The best results were obtained with complexes involving 1-methyl-2-pyrrolidone and hydroxypropylbeta- cyclodextrin, with an increased of benznidazole solubility in 27.9 and 9.4 times, respectively. The complexes effectiveness was proven by dissolution tests, in which the ternary complexes and physical mixtures involving 1-methyl- 2-pyrrolidone and both cyclodextrins investigated showed better results, showing the potential use as novel pharmaceutical ingredient, that leads to increased benznidazole bioavailability

Estudo de compatibilidade e estabilidade térmica do ácido retinóico e hidroquinona por termogravimetria

Retinoic acid (RA) and hydroquinone (HQ) assets are widely used in pharmaceutical and cosmetic formulations, for having depigmenting properties and are largely produced in drugstores. To assist in the development of formulations containing the active RA and HQ National Forms of Brazilian Pharmacopoeia (2005 and 2012 ) proposes formulations with different excipients such as cetyl alcohol (AC), cetostearyl alcohol (ACT), methylparaben (MTP), propyl paraben ( PPB), glycerin (GLY), dipropylene glycol (DPG), imidazolidinil urea ( IMD ), cyclomethicone (CCM ), butylated hydroxytoluene (BHT), octyl stearate (ETO), EDTA, decil oleate (ODC) and hydroxipropymethyl celullose (HPMC). One of the difficulties found in most cosmetic formulations is the large number of incompatibilities between the components of the formulations, so the aim this study was to evaluate thermal stability and interactions between these active pharmaceutical ingredients and excipients. The depigmenting agents were analyzed by DSC and TG and excipients were analyzed by TG. The dynamic thermogravimetric curves were obtained on a SHIMADZU thermobalance, model DTG-60, using an alumina crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-900 ºC, under an atmosphere of nitrogen at 50 mL min-1. The DSC curves were obtained using Shimadzu calorimeter, model DSC-60, using aluminum crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-400ºC. The thermogravimetric and calorimetric curves were analyzed using TASYS software SHIMADZU. In this study no were found interactions between AR and the following excipients: MTP, PPB, IMD, ODC, EDTA, CCM, ETO, HPMC. However, were found interactions with the following excipients: AC, ACT, BHT, GLI and DPG. For HQ were found interactions with IMD and DPG. Interactions remained even changing proportions of the mixtures and the ternary. Thus, the studies conducted with excipients of National Formulary from 2005 and 2012 showed that these new excipients do not interact by thermogravimetry with the active pharmaceutical ingredients of this study

Utilização intracoágulo de espuma fibrinolítica - preparação, caracterização e atividade in vitro de uma espuma de estreptoquinase e proposta de uma nova abordagem terapêutica

Foam was developed as a novel vehicle for streptokinase with the purpose of increasing the contact time and area between the fibrinolytic and the target thrombus, which would lead to a greater therapeutic efficacy at lower doses, decreasing the drug s potential to cause bleeding. Fibrinolytic foams were prepared using CO2 and human albumin (at different v:v ratios), as the gas and liquid phases, respectively, and streptokinase at a low total dose (100,000 IU) was used as fibrinolytic agent conveyed in 1 mL of foam and in isotonic saline solution. The foams were characterized as foam stability and apparent viscosity. The thrombolytic effect of the streptokinase foam was determined in vitro as thrombus lysis and the results were compared to those of a fibrinolytic solution (prepared using the same dose of streptokinase) and foam without the fibrinolytic. In vitro tests were conducted using fresh clots were weighed and placed in test tubes kept at 37 ° C. All the samples were injected intrathrombus using a multiperforated catheter. The results showed that both foam stability and apparent viscosity increased with the increase in the CO2:albumin solution ratio and therefore, the ratio of 3:1 was used for the incorporation of streptokinase. The results of thrombus lysis showed that the streptokinase foam presented the highest thrombolytic activity (44.78 ± 9.97%) when compared to those of the streptokinase solution (32.07 ± 3.41%) and the foam without the drug (19.2 ± 7.19%). We conclude that fibrinolytic foam showed statistically significant results regarding the enhancement of the lytic activity of streptokinase compared to the effect of the prepared saline solution, thus it can be a promising alternative in the treatment of thrombosis. However, in vivo studies are needed in order to corroborate the results obtained in vitro

Dispersões sólidas de sinvastatina: preparação, caracterização, no estado sólido utilizando técnicas emergentes e estudo de estabilidade

This thesis aimed to assess the increase in solubility of simvastatin (SINV) with solid dispersions using techniques such as kneading (MA), co-solvent evaporation (ES), melting carrier (FC) and spray dryer (SD). Soluplus (SOL), PEG 6000 (PEG), PVP K-30 (PVP) e sodium lauryl sulphate (LSS) were used as carriers. The solid dispersions containing PEG [PEG-2(SD)], Soluplus [SOL-2(MA)] and sodium lauryl sulphate [LSS-2(ES)] were presented with a greater increase in solubility (5.02, 5.60 and 5.43 times respectively); analyses by ANOVA between the three groups did not present significant difference (p<0.05). In the phase solubility study, the calculation of the Gibbs free energy (ΔG) revealed that the spontaneity of solubilisation of SINV occurred in the order SOL>PEG >PVP 75%>LSS, always 80%. The phase diagrams of PEG and LSS presented solubilization stoichiometry of type 1:1 (type AL). The diagrams with PVP and SOL tend to 1:2 stoichiometry (type AL + AP). The stability coefficients (Ks) of the phase diagrams revealed that the most stable reactions occurred with LSS and PVP. The solid dispersions were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size distribution (PSD), near-infrared spectroscopy imaging (NIR-CI) and X-ray diffraction of the powder using the Topas software (PDRX-TOPAS). The solid dispersion PEG-2(SD) presented the greatest homogeneity and the lowest degree of crystallinity (18.2%). The accelerated stability study revealed that the solid dispersions are less stable than SINV, with PEG-2(SD) being the least stable, confirmed by FTIR and DSC. The analyses by PDRX-TOPAS revealed the amorphous character of the dispersions and the mechanism of increasing solubility

Efeitos individuais e interativos da diversidade de detritos, contexto e variabilidade ambiental sobre a magnitude e estabilidade do processo de decomposição

Studies on the effects of changes in biodiversity and ecosystem functioning have been a central theme in ecology over the past two decades. Several studies have showed that the diversity of plant debris differently affects the decomposition process in aquatic and terrestrial environments, but we know very about the effects of detritus diversity on decomposition under fluctuating environmental conditions. We tested whether and how the environmental contexts, as well as the dynamic of their alternation, influence the effects of detritus diversity on the decomposition process. We performed a field experiment where we manipulate the litter diversity of 8 species of terrestrial plants decomposing (litterbags) in single and in mixture containing the eight species together in three different environmental contexts: the terrestrial environment (T), aquatic (A) and interface (I) - experimental treatment that simulates variation in flooding regime. We measured the rate of decomposition through the loss of mass of the community and each individual detritus in monocultures and mixtures. Species richness and environmental variability had no effects on the magnitude and stability of the decomposition process. However, there were significant diversity effects on the decomposition of an individual alien species, F. benjamina. Environmental context had significant effects on the magnitude and variability of decomposition. Detritus decomposition was faster and more variable on aquatic, interface and terrestrial conditions, respectively. Our results demonstrate that the diversity of plant detritus has minor effects to the decomposition across disparate environmental conditions and suggest that it is necessary to consider the potential of other abiotic factors in affect the magnitude and variability of the decomposition processes

Estabilidade e robustez de um controlador adaptativo indireto por um modelo de referência e estrutura variável

In this thesis, it is developed the robustness and stability analysis of a variable structure model reference adaptive controller considering the presence of disturbances and unmodeled dynamics. The controller is applied to uncertain, monovariable, linear time-invariant plants with relative degree one, and its development is based on the indirect adaptive control. In the direct approach, well known in the literature, the switching laws are designed for the controller parameters. In the indirect one, they are designed for the plant parameters and, thus, the selection of the relays upper bounds becomes more intuitive, whereas they are related to physical parameters, which present uncertainties that can be known easier, such as resistances, capacitances, inertia moments and friction coefficients. Two versions for the controller algorithm with the stability analysis are presented. The global asymptotic stability with respect to a compact set is guaranteed for both cases. Simulation results under adverse operation conditions in order to verify the theoretical results and to show the performance and robustness of the proposed controller are showed. Moreover, for practical purposes, some simplifications on the original algorithm are developed

Controle preditivo não linear baseado no modelo de Hammerstein com prova de estabilidade

The Predictive Controller has been receiving plenty attention in the last decades, because the need to understand, to analyze, to predict and to control real systems has been quickly growing with the technological and industrial progress. The objective of this thesis is to present a contribution for the development and implementation of Nonlinear Predictive Controllers based on Hammerstein model, as well as to its make properties evaluation. In this case, in the Nonlinear Predictive Controller development the time-step linearization method is used and a compensation term is introduced in order to improve the controller performance. The main motivation of this thesis is the study and stability guarantee for the Nonlinear Predictive Controller based on Hammerstein model. In this case, was used the concepts of sections and Popov Theorem. Simulation results with literature models shows that the proposed approaches are able to control with good performance and to guarantee the systems stability

Modelagem e controle de um microveículo aéreo: uma aplicação de estabilidade robusta com a técnica backstepping em uma estrutura hexarrotor

In this Thesis, the development of the dynamic model of multirotor unmanned aerial vehicle with vertical takeoff and landing characteristics, considering input nonlinearities and a full state robust backstepping controller are presented. The dynamic model is expressed using the Newton-Euler laws, aiming to obtain a better mathematical representation of the mechanical system for system analysis and control design, not only when it is hovering, but also when it is taking-off, or landing, or flying to perform a task. The input nonlinearities are the deadzone and saturation, where the gravitational effect and the inherent physical constrains of the rotors are related and addressed. The experimental multirotor aerial vehicle is equipped with an inertial measurement unit and a sonar sensor, which appropriately provides measurements of attitude and altitude. A real-time attitude estimation scheme based on the extended Kalman filter using quaternions was developed. Then, for robustness analysis, sensors were modeled as the ideal value with addition of an unknown bias and unknown white noise. The bounded robust attitude/altitude controller were derived based on globally uniformly practically asymptotically stable for real systems, that remains globally uniformly asymptotically stable if and only if their solutions are globally uniformly bounded, dealing with convergence and stability into a ball of the state space with non-null radius, under some assumptions. The Lyapunov analysis technique was used to prove the stability of the closed-loop system, compute bounds on control gains and guaranteeing desired bounds on attitude dynamics tracking errors in the presence of measurement disturbances. The controller laws were tested in numerical simulations and in an experimental hexarotor, developed at the UFRN Robotics Laboratory

Desenvolvimento de Modelos no Programa DigSILENT PowerFactoryTM para o Estudo de Estabilidade Transitória em Sistemas Elétricos de Potência com Aerogerador

This work presents a description of models development at DigSILENT PowerFactoryT M program for the transient stability study in power systems with wind turbine. The main goal is to make available means to use a dynamic simulation program in power systems, widely published, and utilize it as a tool that helps in programs results evaluations used for this intent. The process of simulations and analyses results starts after the models setting description phase. The results obtained by the DigSILENT PowerFactoryT M and ATP, program chosen to the validation also international recognized, are compared during this phase. The main tools and guide lines of PowerFactoryT M program use are presented here, directing these elements to the solution of the approached problem. For the simulation it is used a real system which it will be connected a wind farm. Two different technologies of wind turbines were implemented: doublyfed induction generator with frequency converter, connecting the rotor to the stator and to the grid, and synchronous wind generator with frequency converter, interconnecting the generator to the grid. Besides presenting the basic conceptions of dynamic simulation, it is described the implemented control strategies and models of turbine and converters. The stability of the wind turbine interconnected to grid is analyzed in many operational conditions, resultant of diverse kinds of disturbances

Desenvolvimento de modelos no programa digSILENT powerfactoryTM para o estudo de estabilidade transitória em sistemas elétricos de potência com aerogerador

This work presents a description of models development at DigSILENT PowerFactoryTM program for the transient stability study in power systems with wind turbine. The main goal is to make available means to use a dynamic simulation program in power systems, widely published, and utilize it as a tool that helps in programs results evaluations used for this intent. The process of simulations and analyses results starts after the models setting description phase. The results obtained by the DigSILENT PowerFactoryTM and ATP, program chosen to the validation also international recognized, are compared during this phase. The main tools and guide lines of PowerFactoryTM program use are presented here, directing these elements to the solution of the approached problem. For the simulation it is used a real system which it will be connected a wind farm. Two different technologies of wind turbines were implemented: doubly-fed induction generator with frequency converter, connecting the rotor to the stator and to the grid, and synchronous wind generator with frequency converter, interconnecting the generator to the grid. Besides presenting the basic conceptions of dynamic simulation, it is described the implemented control strategies and models of turbine and converters. The stability of the wind turbine interconnected to grid is analyzed in many operational conditions, resultant of diverse kinds of disturbances

Fibras de sisal (Agave sisalana) como isolante térmico de tubulações

In the last decades there was a significant increasing of the numbers of researchers that joint efforts to find alternatives to improve the development of low environmental impact technology. Materials based on renewable resources have enormous potentials of applications and are seen as alternatives for the sustainable development. Within other parameters, the sustainability depends on the energetic efficiency, which depends on the thermal insulation. Alternative materials, including vegetal fibers, can be applied to thermal insulation, where its first goal is to minimize the loss of energy. In the present research, it was experimentally analyzed the thermal behavior of fiber blankets of sisal (Agave sisalana) with and without surface treatment with oxide hidroxide (NaOH). Blankets with two densities (1100/1200 and 1300/1400 g/m2) were submitted to three rates of heat transfer (22.5 W, 40 W and 62.5 W). The analysis of the results allowed comparing the blankets treated and untreated in each situation. Others experiments were carried out to obtain the thermal conductivity (k), heat capacity (C) and the thermal diffusivity (α) of the blankets. Thermo gravimetric analyses were made to the verification of the thermal stability. Based on the results it was possible to relate qualitatively the effect of the heat transfer through the sisal blankets subjected to three heat transfer rates, corresponding to three temperature values (77 °C, 112 °C e 155 °C). To the first and second values of temperature it was verified a considerable reduction on the rate of heat transfer; nevertheless, to the third value of temperature, the surface of the blankets (treated and untreated) in contact with the heated surface of the tube were carbonized. It was also verified, through the analyses of the results of the measurements of k, C e α, that the blankets treated and untreated have values near to the conventional isolating materials, as glass wool and rock wool. It could be concluded that is technically possible the use of sisal blankets as constitutive material of thermal isolation systems in applications where the temperature do not reach values greater than 112 ºC

Envelhecimento ambiental acelerado em PRF a base de tecidos híbridos kevlar/vidro: propriedades e instabilidade estrutural

There are a number of damaging mechanisms that various materials can suffer in service. However, when working with polymer composite materials, this is something that requires analysis, especially when exposed to adverse environmental conditions. Thus, the objective of the present thesis is the study of the direct influence of environmental aging and the form of hybridization of the reinforcement woven on the structural stability, surfacedegradation and fracture process of polymer composites laminates. For this, the development of two polymer composite laminates was necessary, where one of them was reinforced with a bi-directional woven with hybrid strandsofkevlar-49/glass-Efibers, and the other also with a bi-directionalwoven, however with weft and warpformed of alternating strandsof Kevlar-49 fibers and glass-E fiber The reinforcementwoven are industrially manufactured. Both laminates use a polyester resin as a matrixand are made up of four layers each. All laminates were industrially prepared by the hand lay-up method of manufacturing. To do this, test specimens were manufactured of the respective laminates and submitted to environmental aging accelerated through the aging chamber. They were exposed to alternating cycles of UV radiation and moisture (heated steam) for a standard defined period. At the end of the exposure period the specimens were subjected to mechanical tests of uniaxial tensile and bending in three points and to the characterizationsof the fracture and surface deterioration. In addition, they were submitted to a structural degradation assessment by the measurement of mass variation technique (MMVT) and the measurement of thickness variation technique (MTVT), this last technique being developed in this thesis. At the end of the analysis it was observed that the form of hybridization of the reinforcement woven and the aging process directly influence with losses or gain in mechanical properties, with losses in the structural degradation and in the formation and propagation of damage mechanism of the developedcomposite laminates

Efeitos da radiação uv, temperatura e vapor aquecido nos compósitos poliméricos: monitoramento, instabilidade estrutural e fratura

The application of composite materials and in particular the fiber-reinforced plastics (FRP) has gradually conquered space from the so called conventional materials. However, challenges have arisen when their application occurs in equipment and mechanical structures which will be exposed to harsh environmental conditions, especially when there is the influence of environmental degradation due to temperature, UV radiation and moisture in the mechanical performance of these structures, causing irreversible structural damage such as loss of dimensional stability, interfacial degradation, loss of mass, loss of structural properties and changes in the damage mechanism. In this context, the objective of this thesis is the development of a process for monitoring and modeling structural degradation, and the study of the physical and mechanical properties in FRP when in the presence of adverse environmental conditions (ageing). The mechanism of ageing is characterized by controlled environmental conditions of heated steam and ultraviolet radiation. For the research, it was necessary to develop three polymer composites. The first was a lamina of polyester resin reinforced with a short glass-E fiber mat (representing the layer exposed to ageing), and the other two were laminates, both of seven layers of reinforcement, one being made up only of short fibers of glass-E, and the other a hybrid type reinforced with fibers of glass-E/ fibers of curaua. It should be noted that the two laminates have the lamina of short glass-E fibers as a layer of the ageing process incidence. The specimens were removed from the composites mentioned and submitted to environmental ageing accelerated by an ageing chamber. To study the monitoring and modeling of degradation, the ageing cycles to which the lamina was exposed were: alternating cycles of UV radiation and heated steam, a cycle only of UV radiation and a cycle only of heated steam, for a period defined by norm. The laminates have already undergone only the alternating cycle of UV and heated steam. At the end of the exposure period the specimens were subjected to a structural stability assessment by means of the developed measurement of thickness variation technique (MTVT) and the measurement of mass variation technique (MMVT). Then they were subjected to the mechanical tests of uniaxial tension for the lamina and all the laminates, besides the bending test on three points for the laminates. This study was followed by characterization of the fracture and the surface degradation. Finally, a model was developed for the composites called Ageing Zone Diagram (AZD) for monitoring and predicting the tensile strength after the ageing processes. From the results it was observed that the process of degradation occurs Abstract Raimundo Nonato Barbosa Felipe xiv differently for each composite studied, although all were affected in certain way and that the most aggressive ageing process was that of UV radiation, and that the hybrid laminated fibers of glass-E/curaua composite was most affected in its mechanical properties