A new insight about pharmaceutical dosage forms for benzathine penicillin G

In this work, a micellar system of benzathine penicillin G (BPG) in sodium deoxycholate (NaDC) was developed and evaluated physicochemically. The solubility profile of the drug in water and buffer solutions at various pH was determined, as well as its n-octanol/water partition coefficient. The Critical Micellar Concentration of NaDC and its ability to incorporate BPG were also assessed. The study was carried out at low and high ionic strength which was adjusted by the addition of sodium chloride. The results demonstrated the ability of the micellar system to incorporate BPG, as well as to increase its apparent solubility in water. The enhancement of the solubility of BPG by the presence of NaDC micelles could be analyzed quantitatively within the framework of the pseudo-phase model. Concentration analysis showed that the micellar system could attain up to 90% incorporation of BPG. The incorporated drug is expected to exhibit improved stability, since the antibiotic enclosed in the hydrophobic core of micelles is rather shielded from the aqueous external environment

Estudo da moagem de alta energia e sinterização de pós compósitos W-Cu

The Tungsten/copper composites are commonly used for electrical and thermal objectives like heat sinks and lectrical conductors, propitiating an excellent thermal and electrical conductivity. These properties are dependents of the composition, crystallite size and production process. The high energy milling of the powder of W-Cu produces an dispersion high and homogenization levels with crystallite size of W very small in the ductile Cu phase. This work discusses the effect of the HEM in preparation of the W-25Cu composite powders. Three techniques of powder preparation were utilized: milling the dry with powder of thick Cu, milling the dry with powder of fine Cu and milling the wet with powder of thick Cu. The form, size and composition of the particles of the powders milled were observed by scanning electron microscopy (SEM). The X-ray diffraction (XRD) was used to analyse the phases, lattice parameters, size and microstrain of the crystallite. The analyse of the crystalline structure of the W-25Cu powders milled made by Rietveld Method suggests the partial solid solubility of the constituent elements of the Cu in lattice of the W. This analyse shows too that the HEM produces the reduction high on the crystallite size and the increase in the lattice strain of both phases, this is more intense in the phase W

Caracterização de compósitos Nb-20%cu obtidos por moagem de alta energia e sinterizados por fase líquida

In this work, was studied the formation of a composite of the refractory metal niobium with copper, through the process of high-energy milling and liquid phase sintering. The HEM can be used to synthesize composite powders with high homogeneity and fine size particle distribution. It may also produce the solid solubility in immiscible systems such as Nb-Cu, or extend the solubility of systems with limited solubility. Therefore, in the immiscible system Cu-Nb, the high-energy milling was successfully used to obtain the composite powder particles. Initially, the formation of composite particles during the HEM and the effect of preparation technique on the microstructure of the material was evaluated. Four loads of Nb and Cu powders containing 20%wt Cu were synthesized by MAE in a planetary type ball mill under different periods of grinding. The influence of grinding time on the metal particles is evaluated during the process by the withdrawal of samples at intermediate times of milling. After compaction under different forces, the samples were sintered in a vacuum furnace. The liquid phase sintering of these samples prepared by HEM produced a homogeneous and fine grained. The composite particles forming the sintered samples are the addition of a hard phase (Nb) with a high melting point, and a ductile phase (Cu) with low melting point and high thermal and electrical conductivities. Based on these properties, the Nb-Cu system is a potential material for many applications, such as electrical contacts, welding electrodes, coils for generating high magnetic fields, heat sinks and microwave absorbers, which are coupled to electronic devices. The characterization techniques used in this study, were laser granulometry, used to evaluate the homogeneity and particle size, and the X-ray diffraction, in the phase identification and to analyze the crystalline structure of the powders during milling. The morphology and dispersion of the phases in the composite powder particles, as well the microstructures of the sintered samples, were observed by scanning electron microscopy (SEM). Subsequently, the sintered samples are evaluated for density and densification. And finally, they were characterized by techniques of measuring the electrical conductivity and microhardness, whose properties are analyzed as a function of the parameters for obtaining the composite

Novos monômeros obtidos a partir do metacrilato de glicidila, bisfenol A e 4, 4 isopropilidenodicicloexanol : síntese, caracterização estrutural e propriedades de compósitos para utilização em resinas de restauração dental

Nowadays, composite resins are the direct restorative materials more important in dental clinical performance, due to their versatility and aesthetic excellence. Bis-GMA (2,2-bis[4(2-hydroxy-3-metacryloxypropoxy)phenil]propane) is the base monomer more frequently used in restorative composite resins. However, this monomer presents some disadvantages, such as high viscosity and two aromatic rings in its structure that can promote allergic reactions to the humans. In this work, the main purpose was to synthesize new monomers from glycidyl methacrylate to use in dental restorative materials. Structural characterization of the monomers was carried out through FTIR and NMR 1H, and eight composites were produced from the new monomers, by addition of silane-treated alumino silicate particles (inorganic filler) and a photocuring system (camphorquinone and ethyl 4-dimethylaminebenzoate). The composites were analyzed by environmental scanning electronic microscopy and the water sorption and solubility, compressive strength and elastic modulus were determined. A commercial composite resin [Z100 (3M)] was used to comparison effect. The new composites presented general characteristics similar to the commercial ones; however, they didn t present the properties expected. This behavior was attributed to the lower degree of monomer reaction and to the granulometry and size distribution of the mineral filler in the polymeric matrix

Análise comparativa entre simuladores de linha de fluxo e diferenças finitas para um reservatório de petróleo submetido a injeção de água

Water injection is the most widely used method for supplementary recovery in many oil fields due to various reasons, like the fact that water is an effective displacing agent of low viscosity oils, the water injection projects are relatively simple to establish and the water availability at a relatively low cost. For design of water injection projects is necessary to do reservoir studies in order to define the various parameters needed to increase the effectiveness of the method. For this kind of study can be used several mathematical models classified into two general categories: analytical or numerical. The present work aims to do a comparative analysis between the results presented by flow lines simulator and conventional finite differences simulator; both types of simulators are based on numerical methods designed to model light oil reservoirs subjected to water injection. Therefore, it was defined two reservoir models: the first one was a heterogeneous model whose petrophysical properties vary along the reservoir and the other one was created using average petrophysical properties obtained from the first model. Comparisons were done considering that the results of these two models were always in the same operational conditions. Then some rock and fluid parameters have been changed in both models and again the results were compared. From the factorial design, that was done to study the sensitivity analysis of reservoir parameters, a few cases were chosen to study the role of water injection rate and the vertical position of wells perforations in production forecast. It was observed that the results from the two simulators are quite similar in most of the cases; differences were found only in those cases where there was an increase in gas solubility ratio of the model. Thus, it was concluded that in flow simulation of reservoirs analogous of those now studied, mainly when the gas solubility ratio is low, the conventional finite differences simulator may be replaced by flow lines simulator the production forecast is compatible but the computational processing time is lower.

Extração de metais (K, Mg, Ba, Ca, Cr, Mn, Li, Fe) de água produzida utilizando sistema microemulsionado

The produced water is a byproduct formed due to production of petroleum and carries with it a high amount of contaminants such as oil particles in suspension, organic compounds and metals. Thus, these latter pollutants are very difficult to treat because of its high solubility in water. The objective of this work is to use and evaluate a microemulsioned system to remove metals ( K , Mg , Ba , Ca , Cr , Mn , Li , Fe ) of synthetic produced water. For the extraction of metals, it was used a pseudoternary diagram containing the following phases: synthetic produced water as the aqueous phase (AP), hexane as organic phase (OP), and a cosurfactant/surfactant ratio equal to four (C/S = 4) as the third phase, where the OCS (saponified coconut oil) was used as surfactant and n-butanol as cosurfactant. The synthetic produced water was prepared in a bench scale and the region of interest in the diagram for the removal of metals was determined by experimental design called. Ten points located in the phase Winsor II were selected in an area with a large amount of water and small amounts of reagents. The samples were analyzed in atomic absorption spectrometer, and the results were evaluated through a statistical assesment, allowing the efficiency analysis of the effects and their interactions. The results showed percentages of extraction above 90% for the metals manganese, iron, chromium, calcium, barium and magnesium, and around 45% for metals lithium and potassium. The optimal point for the simultaneous removal of metals was calculated using statistical artifact multiple response function (MR). This calculation showed that the point of greatest extraction of metals occurs was the J point, with the composition [72% AP, 9% OP, 19% C/S], obtaining a global extraction percentage about 80%. Considering the aspects analyzed, the microemulsioned system has shown itself to be an effective alternative in the extraction of metals on synthetic produced water remediation

Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

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

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

Preparação e caracterização de sistemas emulsionados lipidicos contendo praziquantel

Praziquantel (PRZ) is the main drug used for treatment of schistosomiasis in Brazil. It is administered by oral rout as tablets. However, has low aqueous solubility which limits this therapeutic success dosage form and availability of liquid forms. The emulsion systems have great potential and represent an interesting strategy to increase the solubility of drugs. The aim of study was the development and characterization of lipid-emulsified liquid systems of the type oil in water (O / W), the base of soybean oil as the internal phase stabilized by surfactants pair Tween® 80 and Span® 80, for improving the phase biopharmaceutical of PRZ. After selecting the best value of Hydrophilic-Lipophilic Balance (HLB = 11), the parameters of the preparation of the formulations were optimized emulsification technique. The emulsions were successfully obtained; the liquid forms provided exhibited Newtonian behavior and an increase in solubility of PRZ higher than 20 times. The accelerated stability study demonstrated the stability of the emulsions and the effect of cosurfactants investigated. The study of the dynamics of interaction between components in the diagram showed pseudoternary phase regions to obtain O/W emulsions, whereas the study of the interaction of the components and their effect on system structure and the efficiency of incorporation of the drug led to systems with an amount of soluble drug even higher (about 1.5%), which demonstrates the potential of this new input mainly for the treatment of schistosomiasis, which resulted in the filing of patent BR 10 2013 0004 55 3

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

Extração do óleo essencial de Cymbopogom winterianus J. com CO2 pressurizado

The extraction with pressurized fluids has become an attractive process for the extraction of essential oils, mainly due the specific characteristics of the fluids near the critical region. This work presents results of the extraction process of the essential oil of Cymbopogon winterianus J. with CO2 under high pressures. The effect of the following variables was evaluated: solvent flow rate (from 0.37 to 1.5 g CO2/min), pressure (66.7 and 75 bar) and temperature (8, 10, 15, 20 and 25 ºC) on the extraction kinetics and the total yield of the process, as well as in the solubility and composition of the C. winterianus essential oil. The experimental apparatus consisted of an extractor of fixed bed and the dynamic method was adopted for the calculation of the oil solubility. Extractions were also accomplished by conventional techniques (steam and organic solvent extraction). The determination and identification of extract composition were done by gas chromatography coupled with a mass spectrometer (GC-MS). The extract composition varied in function of the studied operational conditions and also related to the used extraction method. The main components obtained in the CO2 extraction were elemol, geraniol, citronellol and citronellal. For the steam extraction were the citronellal, citronellol and geraniol and for the organic solvent extraction were the azulene and the hexadecane. The most yield values (2.76%) and oil solubility (2.49x10-2 g oil/ g CO2) were obtained through the CO2 extraction in the operational conditions of T = 10°C, P = 66.7 bar and solvent flow rate 0.85 g CO2/min

Propriedades cerâmicas e imobilização do manganês em cerâmica estrutural

In this work is the addition of a metallic ion, of the metal Manganese, in a clay of Rio Grande do Norte state for structural ceramics use, the objective this study was to assess the evolution of ceramic properties. The clay was characterized by Chemical and Thermal analysis and Xray difraction. The metallic ion was added in the clay as aqueous solutions at concentrations of 100, 150 and 200 mg / L. The molded by extrusion and the burned were temperatures at 850, 950, 1050 and 1150 º C. Was made Chemical Analysis and investigated the following parameters environmental and ceramic: Solubility, Colour, Linear Retraction (%), Water Absorption (%), Gresification Curves, Apparent Porosity (%), Apparent Specific Mass (g/cm3) and Flexion Rupture Module (kgf/cm2). The results showed that increasing the concentration of metallic ion, properties such as Apparent Porosity (%), Water Absorption (%) decreases and the Flexion Rupture Module (kgf/cm2) increases with increasing temperature independent of the concentration of the ion. The gresification curves showed that the optimum firing temperatures were in the range between 950 and 1050 ° C. The evaluation of the properties showed that the ceramic material can be studied its use in solid brick and ceramic materials with structural function of filling. The results of solubility showed that the addition of ion offers no risk to the environment

Avaliação da temperatura de cristalização da parafina em sistemas: parafina, solvente e tensoativo

The formation of paraffin deposits is common in the petroleum industry during production, transport and treatment stages. It happens due to modifications in the thermodynamic variables that alter the solubility of alkanes fractions present in petroleum. The deposition of paraffin can provoke significant and growing petroleum losses, arriving to block the flow, hindering to the production. This process is associated with the phases equilibrium L-S and the stages and nucleation, growth and agglomeration the crystals. That process is function of petroleum intrinsic characteristics and temperature and pressure variations, during production. Several preventive and corrective methods are used to control the paraffin crystallization, such as: use of chemical inhibitors, hot solvents injection, use of termochemistry reactions, and mechanical removal. But for offshore exploration this expensive problem needs more investigation. Many studies have been carried through Wax Appearance Temperature (WAT) of paraffin; therefore the formed crystals are responsible for the modification of the reologics properties of the oil, causing a lot off operational problems. From the determination of the WAT of a system it is possible to affirm if oil presents or not trend to the formation of organic deposits, making possible to foresee and to prevent problems of wax crystallization. The solvent n-paraffin has been widely used as fluid of perforation, raising the production costs when it is used in the removal paraffin deposits, needing an operational substitute. This study aims to determine the WAT of paraffin and the interference off additives in its reduction, being developed system paraffin/solvent/surfactant that propitiates the wax solubilization. Crystallization temperatures in varied paraffin concentrations and different solvents were established in the first stage of the experiments. In the second stage, using the methodology of variation of the photoelectric signal had been determined the temperature of crystallization of the systems and evaluated the interferences of additives to reduction of the WAT. The experimental results are expressed in function of the variations of the photoelectric signals during controlled cooling, innovating and validating this new methodology to determine WAT, relatively simple with relation the other applied that involve specific equipments and of high cost. Through the curves you differentiate of the results had been also identified to the critical stages of growth and agglomeration of the crystals that represent to the saturation of the system, indicating difficulties of flow due to the increase of the density

Determinação experimental e modelagem termodinâmica do ponto de turbidez de sistemas aquosos com tensoativos nonilfenolpolietoxilados

The nonionic surfactants are composed of substances whose molecules in solution, does not ionize. The solubility of these surfactants in water due to the presence of functional groups that have strong affinity for water. When these surfactants are heated is the formation of two liquid phases, evidenced by the phenomenon of turbidity. This study was aimed to determine the experimental temperature and turbidity nonilfenolpoliethoxyled subsequently perform a thermodynamic modeling, considering the models of Flory-Huggins and the empirical solid-liquid equilibrium (SLE). The method used for determining the turbidity point was the visual method (Inoue et al., 2008). The experimental methodology consisted of preparing synthetic solutions of 0,25%, 0,5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12,5%, 15%, 17% and 20% by weight of surfactant. The nonionic surfactants used according to their degree of ethoxylation (9.5, 10, 11, 12 and 13). During the experiments the solutions were homogenized and the bath temperature was gradually increased while the turbidity of the solution temperature was checked visually Inoue et al. (2003). These temperature data of turbidity were used to feed the models evaluated and obtain thermodynamic parameters for systems of surfactants nonilfenolpoliethoxyled. Then the models can be used in phase separation processes, facilitating the extraction of organic solvents, therefore serve as quantitative and qualitative parameters. It was observed that the solidliquid equilibrium model (ESL) was best represented the experimental data.