Thermal behavior and stability of biodegradable spray-dried microparticles containing triamcinolone

Thermal analysis has been widely used for obtaining information about drug-polymer interactions and for pre-formulation studies of pharmaceutical dosage forms. In this work, biodegradable microparticles Of Poly (D,L-lactide-co-glycolide) (PLGA) containing triamcinolone (TR) in various drug:polymer ratios were produced by spray drying. The main purpose of this study was to study the effect of the spray-drying process not only on the drug-polymer interactions but also on the stability of microparticles using differential scanning calorimetry (DSC), thermogravimetry (TG) and derivative thermogravimetry (DTG), X-ray analysis (XRD), and infrared spectroscopy (IR). The evaluation of drug-polymer interactions and the pre-formulation studies were assessed using the DSC, TG and DTG, and IR. The quantitative analysis of drugs entrapped in PLGA microparticles was performed by the HPLC method. The results showed high levels of drug-loading efficiency for all used drug: polymer ratio, and the polymorph used for preparing the microparticles was the form B. The DSC and TG/DTG profiles for drug-loaded microparticles were very similar to those for the physical mixtures of the components. Therefore, a correlation between drug content and the structural and thermal properties of drug-loaded PLGA microparticles was established. These data indicate that the spray-drying technique does not affect the physico-chemical stability of the microparticle components. These results are in agreement with the IR analysis demonstrating that no significant chemical interaction occurs between TR and PLGA in both physical mixtures and microparticles. The results of the X-ray analysis are in agreement with the thermal analysis data showing that the amorphous form of TR prevails over a small fraction of crystalline phase of the drug also present in the TR-loaded microparticles. From the pre-formulation studies, we have found that the spray-drying methodology is an efficient process for obtaining TR-loaded PLGA microparticles. (C) 2008 Elsevier B.V. All rights reserved.

New Relativistic Atomic Natural Orbital Basis Sets for Lanthanide Atoms with Applications to the Ce Diatom and LuF3

New basis sets of the atomic natural orbital (ANO) type have been developed for the lanthanide atoms La-Lu. The ANOs have been obtained from the average density matrix of the ground and lowest excited states of the atom, the positive ions, and the atom in an electric field. Scalar relativistic effects are included through the use of a Douglas-Kroll-Hess Hamiltonian. Multiconfigurational wave functions have been used with dynamic correlation included using second-order perturbation theory (CASSCF/CASPT2). The basis sets are applied in calculations of ionization energies and some excitation energies. Computed ionization energies have an accuracy better than 0.1 eV in most cases. Two molecular applications are inluded as illustration: the cerium diatom and the LuF3 molecule. In both cases it is shown that 4f orbitals are not involved in the chemical bond in contrast to an earlier claim for the latter molecule.

Thermal analysis of biodegradable microparticles containing ciprofloxacin hydrochloride obtained by spray drying technique

Thermal analysis has been extensively used to obtain information about drug-polymer interactions and to perform pre-formulation studies of pharmaceutical dosage forms. In this work, biodegradable microparticles of poly(D,L-lactide-co-glycolide) (PLGA) containing ciprofloxacin hydrochloride (CP) in various drug:polymer ratios were obtained by spray drying. The main purpose of this study was to investigate the effect of the spray drying process on the drug-polymer interactions and on the stability of microparticles using differential scanning calorimetry (DSC), thermogravimetry (TG) and derivative thermogravimetry (DTG) and infrared spectroscopy (IR). The results showed that the high levels of encapsulation efficiency were dependant on drug:polymer ratio. DSC and TG/DTG analyses showed that for physical mixtures of the microparticles components the thermal profiles were different from those signals obtained with the pure substances. Thermal analysis data disclosed that physical interaction between CP and PLGA in high temperatures had occurred. The DSC and TG profiles for drug-loaded microparticles were very similar to the physical mixtures of components and it was possible to characterize the thermal properties of microparticles according to drug content. These data indicated that the spray dryer technique does not affect the physicochemical properties of the microparticles. In addition, the results are in agreement with IR data analysis demonstrating that no significant chemical interaction occurs between CP and PLGA in both physical mixtures and microparticles. In conclusion, we have found that the spray drying procedure used in this work can be a secure methodology to produce CP-loaded microparticles. (C) 2007 Elsevier B.V. All rights reserved.

Development of a fast capillary electrophoresis method for the determination of propranolol-Total analysis time reduction strategies

The aim of this study was to develop a fast capillary electrophoresis method for the determination of propranolol in pharmaceutical preparations. In the method development the pH and constituents of the background electrolyte were selected using the effective mobility versus pH curves. Benzylamine was used as the internal standard. The background electrolyte was composed of 60 mmol L(-1) tris(hydroxymethyl)aminomethane and 30 mmol L(-1) 2-hydroxyisobutyric acid,at pH 8.1. Separation was conducted in a fused-silica capillary (32 cm total length and 8.5 cm effective length, 50 mu m I.D.) with a short-end injection configuration and direct UV detection at 214 nm. The run time was only 14 s. Three different strategies were studied in order to develop a fast CE method with low total analysis time for propranolol analysis: low flush time (Lflush) 35 runs/h, without flush (Wflush) 52 runs/h, and Invert (switched polarity) 45 runs/h. Since the three strategies developed are statistically equivalent, Mush was selected due to the higher analytical frequency in comparison with the other methods. A few figures of merit of the proposed method include: good linearity (R(2) > 0.9999); limit of detection of 0.5 mg L(-1): inter-day precision better than 1.03% (n = 9) and recovery in the range of 95.1-104.5%. (C) 2009 Elsevier B.V. All rights reserved.

Health and quality of care from older peoples' and formal caregivers' perspective

Aim: The overall aim of this thesis was to gain a deeper understanding of older people's view of health and care while dependent on community care. Furthermore to describe and compare formal caregivers' perceptions of quality of care, working conditions, competence, general health, and factors associated with quality of care from the caregivers' perspective. Method: Qualitative interviews were conducted with 19 older people in community care who were asked to describe what health and ill health((I), good and bad care meant for them (II). Data were analyzed using content analysis (I) and a phenomenological analysis (II). The formal caregivers; 70 nursing assistants (NAs) 163 enrolled nurses (ENs) and 198 registered nurses (RNs), answered a questionnaire consisting of five instruments: quality of care from the patient's perspective modified to formal caregivers, creative climate questionnaire, stress of conscience, health index, sense of coherence and items on education and competence (III). Statistical analyses were performed containing descriptive statistics, and comparisons between the occupational groups were made using Kruskal-Wallis ANOVA, Mann-Whitney U-test and Pearson's Chi-square test (III). Pearson's  product moment correlation analysis and multiple regression analysis were performed studying the associations between organizational climate, stress of conscience, competence, general health and sense of coherence with quality of care (IV). Results: The older people's health and well-being were related to their own ability to adapt to and compensate for their disabilities and was described as negative and positive poles of autonomy vs. dependence, togetherness vs. being an onlooker, security vs. insecurity and tranquility vs. disturbance (I).  The meaning of good care (II) was that the formal caregivers respected the older people as unique individuals, having the opportunity to live their lives as usual and receiving a safe and secure care. Good care could be experienced when the formal caregivers had adequate knowledge and competence in caring for older people, adequate time and continuity in the care organization (II). Formal caregivers reported higher perceived quality of care in the dimensions medical-technical competence and physical-technical conditions than in identity-oriented approach and socio-cultural atmosphere (III). In the organizational climate three of the dimensions were close to the value of a creative climate and in seven near a stagnant climate. The formal caregivers reported low rate of stress of conscience. The RNs reported to a higher degree than the NAs/ENs a need to gain more knowledge, but the NAs and the ENs more often received training during working hours. The RNs reported lower emotional well-being than the NAs/ENs (III). The formal caregivers' occupation, organizational climate and stress of conscience were associated with perceived quality of care (IV). Implications: The formal caregivers should have an awareness of the importance of kindness and respect, supporting the older people to retain control over their lives. The nursing managers should employ highly competent and adequate numbers of skilled formal caregivers, organize formal caregivers having round the clock continuity. Improvements of organizational climate and stress of conscience are of importance for good quality of care.

Índices antecedentes e coincidentes da atividade econômica brasileira:uma aplicação da análise de correlação canônica

This paper uses canonical correlation analisys to identify leading and coincident indicators of economic activity in Brazil. ln contrast with the traditional literature on the subject, no restrictions are made regarding the number of common cycles that are necessary to explain the complete cyclical behavior of the coincident variables. For the brazillian data, it is found that three common cycles exhaust all the cyclical pattern of economic activity. Based on the methodology developed here, it is also sugested an alternative chronology of the recent brazillian recessions.

The missing link: using the NBER recession indicator to construct coincident and leading indices economic activity

We use the information content in the decisions of the NBER Business Cycle Dating Committee to construct coincident and leading indices of economic activity for the United States. We identify the coincident index by assuming that the coincident variables have a common cycle with the unobserved state of the economy, and that the NBER business cycle dates signify the turning points in the unobserved state. This model allows us to estimate our coincident index as a linear combination of the coincident series. We establish that our index performs better than other currently popular coincident indices of economic activity.

The missing link: using the NBER recession indicator to construct coincident and leading indices economic activity

We use the information content in the decisions of the NBER Business Cycle Dating Committee to construct coincident and leading indices of economic activity for the United States. We identify the coincident index by assuming that the coincident variables have a common cycle with the unobserved state of the economy, and that the NBER business cycle dates signify the turning points in the unobserved state. This model allows us to estimate our coincident index as a linear combination of the coincident series. We establish that our index performs better than other currently popular coincident indices of economic activity.

The missing link: using the NBER recession indicator to construct coincident and leading indices economic activity

We use the information content in the decisions of the NBER Business Cycle Dating Committee to construct coincident and leading indices of economic activity for the United States. We identify the coincident index by assuming that the coincident variables have a common cycle with the unobserved state of the economy, and that the NBER business cycle dates signify the turning points in the unobserved state. This model allows us to estimate our coincident index as a linear combination of the coincident series. We compare the performance of our index with other currently popular coincident indices of economic activity.

Unemployment insurance an analysis of optimal mechanisms under aggregate shocks

The purpose of this work is to provide a brief overview of the literature on the optimal design of unemployment insurance systems by analyzing some of the most influential articles published over the last three decades on the subject and extend the main results to a multiple aggregate shocks environment. The properties of optimal contracts are discussed in light of the key assumptions commonly made in theoretical publications on the area. Moreover, the implications of relaxing each of these hypothesis is reckoned as well. The analysis of models of only one unemployment spell starts from the seminal work of Shavell and Weiss (1979). In a simple and common setting, unemployment benefits policies, wage taxes and search effort assignments are covered. Further, the idea that the UI distortion of the relative price of leisure and consumption is the only explanation for the marginal incentives to search for a job is discussed, putting into question the reduction in labor supply caused by social insurance, usually interpreted as solely an evidence of a dynamic moral hazard caused by a substitution effect. In addition, the paper presents one characterization of optimal unemployment insurance contracts in environments in which workers experience multiple unemployment spells. Finally, an extension to multiple aggregate shocks environment is considered. The paper ends with a numerical analysis of the implications of i.i.d. shocks to the optimal unemployment insurance mechanism.

A representação social do fenômeno participativo em organizações publicas do Rio de Janeiro

O presente trabalho, tomando como referencial a teoria das representações sociais, propõe-se a esboçar, a partir dos resultados de uma pesquisa empírica realizada junto a uma amostra privilegiada de servidores públicos, o campo comunicacional pelos quais se define o lugar da participação no contexto da administração pública do Estado. No âmbito teórico destacou-se a relação entre representação social e comportamento, conferindo uma maior ênfase na análise das propriedades estruturais da representação através da identificação de seu núcleo central e de seu sistema periférico associado. Os resultados indicam que, longe de estimular práticas corporativas, a adoção de formas participativas de gestão pode contribuir para a construção de um modelo de administração pública que responda aos requisitos de eficiência, eficácia e efetividade.

Valores, atitudes e intenção empreendedora: um estudo com universitários brasileiros e cabo-verdianos

A presente pesquisa apresentou como seu objetivo principal verificar as relações entre valores, atitude em relação ao empreendedorismo (AE) e intenção empreendedora (IE) em um estudo comparativo com universitários de graduação em Administração das Cinco Regiões Brasileiras e Cabo Verde. O instrumento de pesquisa foi composto por um questionário sócio demográfico, a escala de Valores Humanos – Questionário de Perfis de Valores de Schwartz(2001) e o Questionário de Intenção Empreendedora de Liñán & Chen (2009). Após o consentimento livre e informado, os alunos responderam o instrumento de pesquisa, perfazendo um total de 1561 respostas válidas. Os dados foram tabulados e analisados nos Softwares: SPSS 21 e AMOS 21 para a produção de Estatísticas Descritivas, Análises de Confiabilidade, Análises de Correlação, Análise de Variância (ANOVA), Gráficos, Análise Fatorial Confirmatória e Modelagem de Equações Estruturais (SEM). Os modelos utilizaram a Teoria de Ação Racional (FISHBEIN & AJZEN,1971) e Teoria do Comportamento Planejado(AJZEN,1991), testando o impacto dos valores nas atitudes e intenções. Os resultados indicaram que os valores de Estimulação, Poder e Hedonismo foram tiveram os maiores efeitos na IE e na AE. Diferenças significativas foram encontradas entre os gêneros, com os homens apresentando maior IE e AE. Diferenças regionais foram encontradas. Limitações, implicações práticas e teóricas, além de sugestões para pesquisas futuras são apresentadas.

Essays on illiquidity premium

This dissertation is composed of three related essays on the relationship between illiquidity and returns. Chapter 1 describes the time-series properties of the relationship between market illiquidity and market return using both yearly and monthly datasets. We find that stationarized versions of the illiquidity measure have a positive, significant, and puzzling high premium. In Chapter 2, we estimate the response of illiquidity to a shock to returns, assuming that causality runs from returns to illiquidity and find that an increase in firms' returns lowers illiquidity. In Chapter 3 we take both effects into account and account for the endogeneity of returns and illiquidity to estimate the liquidity premium. We find evidence that the illiquidity premium is a smaller than the previous evidence suggests. Finally, Chapter 4 shows topics for future research where we describe a return decomposition with illiquidity costs.

New method for determination of (E)resveratrol in wine based on microextraction using packed sorbent and ultra-performance liquid chromatography

An ultra-fast and improved analytical methodology based on microextraction by packed sorbent (MEPS) combined with ultra-performance LC (UPLC) was developed and validated for determination of (E)-resveratrol in wines. Important factors affecting the performance of MEPS such as the type of sorbent material (C2, C8, C18, SIL, and M1), number of extraction cycles, and sample volume were studied. The optimal conditions of MEPS extraction were obtained using C8 sorbent and small sample volumes (50–250mL) in one extraction cycle (extract–discard) and in a short time period (about 3 min for the entire sample preparation step). (E)-Resveratrol was eluted by 1 250mL of the mixture containing 95% methanol and 5% water, and the separation was carried out on a highstrength silica HSS T3 analytical column (100 mm 2.1 mm, 1.8mm particle size) using a binary mobile phase composed of aqueous 0.1% formic acid (eluent A) and methanol (eluent B) in the gradient elution mode (10 min of total analysis). The method was fully validated in terms of linearity, detection (LOD) and quantification (LOQ) limits, extraction yield, accuracy, and inter/intra-day precision, using a Madeira wine sample (ET) spiked with (E)-resveratrol at concentration levels ranging from 5 to 60mg/mL. Validation experiments revealed very good recovery rate of 9575.8% RSD, good linearity with r2 values 40.999 within the established concentration range, excellent repeatability (0.52%), and reproducibility (1.67%) values (expressed as RSD), thus demonstrating the robustness and accuracy of the MEPSC8/UPLC-photodiode array (PDA) method. The LOD of the method was 0.21mg/mL, whereas the LOQ was 0.68mg/mL. The validated methodology was applied to 30 commercial wines (24 red wines and six white wines) from different grape varieties, vintages, and regions. On the basis of the analytical validation, the MEPSC8/UPLC-PDA methodology shows to be an improved, sensitive, and ultra-fast approach for determination of (E)-resveratrol in wines with high resolving power within 6 min.

Development of a novel microextraction by packed sorbent-based approach followed by ultrahigh pressure liquid chromatography as a powerful technique for quantification phenolic constituents of biological interest in wines

A novel analytical approach, based on a miniaturized extraction technique, the microextraction by packed sorbent (MEPS), followed by ultrahigh pressure liquid chromatography (UHPLC) separation combined with a photodiode array (PDA) detection, has been developed and validated for the quantitative determination of sixteen biologically active phenolic constituents of wine. In addition to performing routine experiments to establish the validity of the assay to internationally accepted criteria (linearity, sensitivity, selectivity, precision, accuracy), experiments are included to assess the effect of the important experimental parameters on the MEPS performance such as the type of sorbent material (C2, C8, C18, SIL, and M1), number of extraction cycles (extract-discard), elution volume, sample volume, and ethanol content, were studied. The optimal conditions of MEPS extraction were obtained using C8 sorbent and small sample volumes (250 μL) in five extraction cycle and in a short time period (about 5 min for the entire sample preparation step). The wine bioactive phenolics were eluted by 250 μL of the mixture containing 95% methanol and 5% water, and the separation was carried out on a HSS T3 analytical column (100 mm × 2.1 mm, 1.8 μm particle size) using a binary mobile phase composed of aqueous 0.1% formic acid (eluent A) and methanol (eluent B) in the gradient elution mode (10 min of total analysis). The method gave satisfactory results in terms of linearity with r2-values > 0.9986 within the established concentration range. The LOD varied from 85 ng mL−1 (ferulic acid) to 0.32 μg mL−1 ((+)-catechin), whereas the LOQ values from 0.028 μg mL−1 (ferulic acid) to 1.08 μg mL−1 ((+)-catechin). Typical recoveries ranged between 81.1 and 99.6% for red wines and between 77.1 and 99.3% for white wines, with relative standard deviations (RSD) no larger than 10%. The extraction yields of the MEPSC8/UHPLC–PDA methodology were found between 78.1 (syringic acid) and 99.6% (o-coumaric acid) for red wines and between 76.2 and 99.1% for white wines. The inter-day precision, expressed as the relative standard deviation (RSD%), varied between 0.2% (p-coumaric and o-coumaric acids) and 7.5% (gentisic acid) while the intra-day precision between 0.2% (o-coumaric and cinnamic acids) and 4.7% (gallic acid and (−)-epicatechin). On the basis of analytical validation, it is shown that the MEPSC8/UHPLC–PDA methodology proves to be an improved, reliable, and ultra-fast approach for wine bioactive phenolics analysis, because of its capability for determining simultaneously in a single chromatographic run several bioactive metabolites with high sensitivity, selectivity and resolving power within only 10 min. Preliminary studies have been carried out on 34 real whole wine samples, in order to assess the performance of the described procedure. The new approach offers decreased sample preparation and analysis time, and moreover is cheaper, more environmentally friendly and easier to perform as compared to traditional methodologies.