Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems

A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.

Síntese de derivados de adenina e guanina

Tese de Doutoramento em Ciências (Especialidade em Química)

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Validation of the Portuguese version of the Evidence-Based Practice Questionnaire

OBJECTIVES: To describe the process of translation and linguistic and cultural validation of the Evidence Based Practice Questionnaire for the Portuguese context: Questionário de Eficácia Clínica e Prática Baseada em Evidências (QECPBE). METHOD: A methodological and cross-sectional study was developed. The translation and back translation was performed according to traditional standards. Principal Components Analysis with orthogonal rotation according to the Varimax method was used to verify the QECPBE's psychometric characteristics, followed by confirmatory factor analysis. Internal consistency was determined by Cronbach's alpha. Data were collected between December 2013 and February 2014. RESULTS: 358 nurses delivering care in a hospital facility in North of Portugal participated in the study. QECPBE contains 20 items and three subscales: Practice (α=0.74); Attitudes (α=0.75); Knowledge/Skills and Competencies (α=0.95), presenting an overall internal consistency of α=0.74. The tested model explained 55.86% of the variance and presented good fit: χ2(167)=520.009; p = 0.0001; χ2df=3.114; CFI=0.908; GFI=0.865; PCFI=0.798; PGFI=0.678; RMSEA=0.077 (CI90%=0.07-0.08). CONCLUSION: confirmatory factor analysis revealed the questionnaire is valid and appropriate to be used in the studied context.

Ultrasound enhances lipase-catalyzed synthesis of poly (ethylene glutarate)

The present work explores the best conditions for the enzymatic synthesis of poly (ethylene glutarate) for the first time. The start-up materials are the liquids; diethyl glutarate and ethylene glycol diacetate, without the need of addition of extra solvent. The reactions are catalyzed by lipase B from Candida antarctica immobilized on glycidyl methacrylate-ter-divinylbenzene-ter-ethylene glycol dimethacrylate at 40 °C during 18 h in water bath with mechanical stirring or 1 h in ultrasonic bath followed by 6 h in vacuum in both the cases for evaporation of ethyl acetate. The application of ultrasound significantly intensified the polyesterification reaction with reduction of the processing time from 24 to 7 h. The same degree of polymerization was obtained for the same enzyme loading in less time of reaction when using the ultrasound treatment. The degree of polymerization for long-term polyesterification was improved approximately 8-fold due to the presence of sonication during the reaction. The highest degree of polymerization achieved was 31, with a monomer conversion of 96.77%. The ultrasound treatment demonstrated to be an effective green approach to intensify the polyesterification reaction with enhanced initial kinetics and high degree of polymerization.

Estudo de betumes modificados recuperados de misturas produzidas pelo método húmido e pelo método seco

Dissertação de mestrado integrado em Engenharia Civil

Development of polymeric nanoparticles containing neuroprotective compounds of Hypericum perforatum

Tese de Doutoramento em Biologia das Plantas - MAP BIOPLANT

Exploring the factor structure of neurocognitive measures in older individuals

Here we focus on factor analysis from a best practices point of view, by investigating the factor structure of neuropsychological tests and using the results obtained to illustrate on choosing a reasonable solution. The sample (n=1051 individuals) was randomly divided into two groups: one for exploratory factor analysis (EFA) and principal component analysis (PCA), to investigate the number of factors underlying the neurocognitive variables; the second to test the "best fit" model via confirmatory factor analysis (CFA). For the exploratory step, three extraction (maximum likelihood, principal axis factoring and principal components) and two rotation (orthogonal and oblique) methods were used. The analysis methodology allowed exploring how different cognitive/psychological tests correlated/discriminated between dimensions, indicating that to capture latent structures in similar sample sizes and measures, with approximately normal data distribution, reflective models with oblimin rotation might prove the most adequate.

Effect of sodium chloride on solutesolvent interactions in aqueous polyethylene glycolsodium sulfate two-phase systems

Partition behavior of eight small organic compounds and six proteins was examined in poly(ethylene glycol)-8000sodium sulfate aqueous two-phase systems containing 0.215 M NaCl and 0.5 M osmolyte (sorbitol, sucrose, TMAO) and poly(ethylene glycol)-10000sodium sulfate0.215 M NaCl system, all in 0.01 M sodium phosphate buffer, pH 6.8. The differences between the solvent properties of the coexisting phases (solvent dipolarity/polarizability, hydrogen bond donor acidity, and hydrogen bond acceptor basicity) were characterized with solvatochromic dyes using the solvatochromic comparison method. Differences between the electrostatic properties of the phases were determined by analysis of partitioning of sodium salts of dinitrophenylated (DNP-) amino acids with aliphatic alkyl side-chain. The partition coefficients of all compounds examined (including proteins) were described in terms of solutesolvent interactions. The results obtained in the study show that solutesolvent interactions of nonionic organic compounds and proteins in polyethylene glycolsodium sulfate aqueous two-phase system change in the presence of NaCl additive.

Development of a poly(L-Lactic acid) based drug release system

Dissertação de mestrado em Biofísica e Bionanossistemas

Desenvolvimento de membranas poliméricas baseadas em Poli(fluoreto de vinilideno) para a filtração de materiais biológicos

Dissertação de mestrado em Biofísica e Bionanossistemas

Desenvolvimento e validação de um método para a caracterização de vinhos por HPLC-DAD

Dissertação de mestrado em Técnicas de Caracterização e Análise Química

QRS Voltage-Duration Product in the Identification of Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats

OBJECTIVE - Evaluation of the performance of the QRS voltage-duration product (VDP) for detection of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). METHODS - Orthogonal electrocardiograms (ECG) were recorded in male SHR at the age of 12 and 20 weeks, when systolic blood pressure (sBP) reached the average values of 165±3 mmHg and 195±12 mmHg, respectively. Age- and sex- matched normotensive Wistar Kyoto (WKY) rats were used as controls. VDP was calculated as a product of maximum QRS spatial vector magnitude and QRS duration. Left ventricular mass (LVM) was weighed after rats were sacrificed. RESULTS - LVM in SHR at 12 and 20 weeks of age (0.86±0.05 g and 1.05±0.07 g, respectively) was significantly higher as compared with that in WKY (0.65±0.07 g and 0.70±0.02 g). The increase in LVM closely correlated with the sBP increase. VDP did not reflect the increase in LVM in SHR. VDP was lower in SHR as compared with that in WKY, and the difference was significant at the age of 20 weeks (18.2mVms compared with 10.7mVms, p<0.01). On the contrary, a significant increase in the VDP was observed in the control WKY at the age of 20 weeks without changes in LVM. The changes in VDP were influenced mainly by the changes in QRSmax. CONCLUSION - LVM was not the major determinant of QRS voltage changes and consequently of the VDP. These data point to the importance of the nonspatial determinants of the recorded QRS voltage in terms of the solid angle theory.

Theoretische und experimentelle Studie der Gradienten-Gegenstromchromatographie unter linearen Bedingungen

Simulated Moving Bed (SMB)-Chromatography, solvent gradients, mathematical modelling for linear isotherms

Envelhecimento das aguardentes

1 - Colour, by itself, does not constitute a solid ground for judging of the age of a brandy because the more or less pronounced colour it acquires through aging can also be obtained by the addition of oack essence to newly distilled brandy. 2 - Urder the same conditions, colour intensity of a brandy wiU depend upon the nature of the wood and the condition of the storage. 3 - In accordance with the experimental results obtained by the present writers it rests no doubt that fermentation facility ferment resistence, produce and quality of the brendy all are factors depending upon the variety of the sugar cane. In addition, the authors presume that the variety of sugar cane has also influence upon the alteration of composition of the brandy submitted to aging. 4 - All aging phenomena of the brandy are accompanied by volume decreasing, what happens in a slow and continuous manner depending upon storage and environment conditions 5 - During brandy aging the alcoholic degree is greatly af- fected by evaporation, increasing or decreasing in accordance to the hygrometric state of the air and the teriperature in the place where the tuns are stored. 6 - The specific weight of the brandy is inversely proportio- nal to its alcoholic degree, but directly proportional to the extracts since the latter indicates the amount of dissolved residues. 7 - Brandy which shows high specific weight together with high alcoholic degree cannot be considered as aged. It may, however, be takens for brandy artificially coloved in order to conceal its actual age. 8 - The amount of extracts increases with aging, since it is the result of the solvent action of the brandy upon the soluble extractive substances of the wood. Notwithstanding that the extract, considered alone, has no value in determining the age of a brandy, since nothing easier is ohan to nake it change artificially. 9 -During aging the brandy get acidity in physiological as well as in physical way, but never by the action of microorganisms. 10 - The estturs produced during aging by the action of acids upon alcohols are the mean factors of the savour (bouquet) of a brandy and therefore every thing shall be done tor fhr estherification of a preserved brandy being not limited. 11 - Aeration increases esther formation, reduces the aging- time and turn better the taste qualities of the brandy. 12 - Due to the great proportion of high alcohols ordinarily found in the brandy, their analytical discrimination will be greatly important. 13 - The high alcohols are not responsable for the disastrous consequences of the alcoholism, but the high percentage of uthyl alcohol present in the brandy. 14 - The aldehydes appear always in high rate in the brazilian brandys in consequence of some intermediary products of the oxydation of the alcohols being left in the brandys during aging. 15 - The age has little or no influence on the quantity of phurphurol present in a brandy whose amount varies greatly the manner in which the wines to be distilled are treated. Wines centrifugalized or filtered before distillation always give rise to brandys poorer in phurphurol as compared with those distilled without these treatments. 16 - Though greatly variable, brandys of good qualities generally show a high residues coefficient, never under 200 mmg 17 - Lusson - Rocques oxydation coefficient cannot be indis- criminately applied to any brandy class, being, on the contrary, specifically destined to cognacs.