Aplicação do delineamento simplex-centroide no estudo da cinética da oxidação de biodiesel B100 em mistura com antioxidantes sintéticos

Antioxidants are an alternative to prevent or slow the degradation of the biofuel. In this study, it was evaluated the oxidative stability of B100 biodiesel from soybean oil in the presence of three commercial synthetic antioxidants, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and tert-butylhydroquinone (TBHQ), pure or blended, from the experimental design of simplex-centroid mixture. The reaction order and rate constant were also calculated for all tests. The treatment containing pure TBHQ proved to be the most effective, proven by design, the optimum mix obtained and the rate constant. Binary and ternary mixtures containing TBHQ also showed appreciable antioxidant effect.

Sistema de análises em fluxo polivalente para a determinação espectrofotométrica de fármacos

A flow system based on the sandwich technique is proposed for the sequential determination of ascorbic acid, dipyrone, acetylcysteine, captopril and paracetamol. The procedure is based on the reduction of Cu(II) by the analytes followed by the spectrophotometric measurement of the complex of Cu(I) with 2,2'-biquinoline 4,4'-dicarboxylic acid. Linear responses were achieved in the µmol L-1 range, with coefficients of variation better than 1.7%. Sampling rate was estimated as 60 determinations per hour, consuming 230 µg of BQA and generating 2.5 mL of waste per determination. Results for commercial samples agreed with those obtained by procedures recommended by the American and European pharmacopeias at the 95% confidence level.

Análise térmica aplicada a fármacos e formulações farmacêuticas na indústria farmacêutica

Several matters of the pharmaceutical demonstrate the great importance of thermal analysis application, especially TG and DSC for the pharmaceutical industry future, namely: characterization of the drugs with the thermal events definition, in studies of drug purity, in the polymorphs identification, in compatibility studies of solid dosage pharmaceutical formulations, in drugs and pharmaceutical formulations thermal stability, and in determination of shelf life for isothermal degradation kinetics by extrapolation using the Arrhenius equation. Thus, the test results obtained from thermal analysis are directly related to the quality of a pharmaceutical product, whether the stability or bioavailability of the pharmaceutical product.

Integração das técnicas de triagem virtual e triagem biológica automatizada em alta escala: oportunidades e desafios em P&D de fármacos

High-throughput screening (HTS) and virtual screening (VS) are useful methods employed in drug discovery, allowing the identification of promising hits for lead optimization. The efficiency of these approaches depends on a number of factors, such as the organization of high quality databases of compounds and the parameterization of essential components of the screen process. This brief review presents the basic principles of the HTS and VS methods, as well as a perspective of the utility and integration of these drug design approaches, highlighting current opportunities and future challenges in medicinal chemistry.

Anemia falciforme: desafios e avanços na busca de novos fármacos

Sickle Cell Disease (SCD) is a disease characterized by a punctual mutation (GTG - GAG) in the sixth codon of the gamma globin gene leading to a substitution of glutamic acid by a valine in the β chain of hemoglobin. Despite the huge progress on the molecular knowledge of the disease in recent years, few therapeutic resources were developed. Currently, the treatment is mainly done with the anticancer agent hydroxyurea. This review summarizes current knowledge about possible targets and new approaches to the discovery new compounds to treat the symptoms of SCD.

Determinação rápida de fármacos básicos em plasma por cromatografia a gás com detector de nitrogênio e fósforo

A simple and fast method for determination of 40 basic drugs in human plasma employing gas-chromatography with nitrogen-phosphorus detection was developed and validated. Drugs were extracted from 800 µL of plasma with 250 µL of butyl acetate at basic pH. Aliquots of the organic extract were directly injected on a column with methylsilicone stationary phase. Total chromatographic run time was 25 min. All compounds were detected in concentrations ranging from therapeutic to toxic levels, with intermediate precision CV% below 11.2 and accuracy in the range of 92-114%.

Nanoemulsões como sistemas de liberação parenteral de fármacos

Lipid nanoemulsions have recently been proposed as parenteral delivery systems for poorly-soluble drugs. These systems consist of nanoscale oil/water dispersions stabilized by an appropriate surfactant system in which the drug is incorporated into the oil core and/or adsorbed at the interface. This article reviews technological aspects of such nanosystems, including their composition, preparation methods, and physicochemical properties. From this review, it was possible to identify five groups of nanoemulsions based on their composition. Biopharmaceutical aspects of formulations containing some commercially available drugs (diazepam, propofol, dexamethasone, etomidate, flurbiprofen and prostaglandin E1) were then discussed.

Desenvolvimento, produção e caracterização de nanocristais de fármacos pouco solúveis

Poorly soluble drugs have low bioavailability, representing a major challenge for the pharmaceutical industry. Processing drugs into the nanosized range changes their physical properties, and these are being used in pharmaceutics to develop innovative formulations known as Nanocrystals. Use of nanocrystals to overcome the problem of low bioavailability, and their production using different techniques such as microfluidization or high pressure homogenization, was reviewed in this paper. Examples of drugs, cosmetics and nutraceutical ingredients were also discussed. These technologies are well established in the pharmaceutical industry and are approved by the Food and Drug Administration.

Comparação dos métodos de determinação da estabilidade oxidativa de biodiesel B100, em mistura com antioxidantes sintéticos: aplicação do delineamento simplex-centroide com variável de processo

The Rancimat and accelerated stove tests were used to determine the oxidative stability of B100 biodiesel mixed with synthetic antioxidants. The predictive equations, with process variable, were obtained by applying a simplex-centroid design. Regardless of the antioxidant used, all assays carried out with the accelerated stove test presented storage time longer than 177.88 d, the greatest value obtained by applying the Rancimat test. The t test, applied to the parameters containing the process variable, showed a statistically significant difference (at the level of 5%) between the methods used.

Fármacos multifuncionais: monoamina oxidase e α-sinucleína como alvos terapêuticos na doença de Parkinson

Parkinson's disease (PD) is a neurodegenerative disorder associated to selective degeneration of dopaminergic neurons caused by an intricate relationship among dopamine metabolism, oxidative stress and α-synuclein fibrillation. Most therapies for PD have focused on dopamine replacement through the use of both monoamine oxidase inhibitors (MAOIs) and dopamine precursor L-dopa. Interestingly, certain MAOIs have a broad spectrum of action including anti-fibrillogenic properties in α-synuclein aggregation. Herein we revisit the chemical properties of MAOIs and their action on important targets associated with PD, notably α-synuclein fibrillation and dopamine metabolism, discussing the strategies associated with the development of multi-target drugs for neurodegenerative diseases.

Descriptores globales y locales de la reactividad para el diseño de nuevos fármacos anticancerosos basados en cis-platino(II)

Density functional theory was used to investigate the global and local reactivity of some cis-platinum(II) complexes including anticancer drugs, such as cisplatin and carboplatin. Calculated equilibrium geometries at mPW1PW/LANL2DZ* are in close agreement with their available X-ray data. We develop three new local reactivity descriptors: atomic descriptor of philicity, atomic descriptor group and atomic descriptor of philicity group for determining chemical reactivity and selectivity of the studied complexes. This contribution on chemical reactivity allow us to establish qualitative trends, which enable our descriptors for use in rational platinum based anticancer drug design.

A influência da piperina na biodisponibilidade de fármacos: uma abordagem molecular

Piperine is the major alkaloid of Piper nigrum Linn., used as a spice and in folk medicine. We present a molecular docking study supporting experimental data on the enhancement in bioavailability of propranolol, theophylline, phenytoin, nevirapine, nimesulide, pyrazinamide, carbamazepine, and spartein in the presence of piperine. The complex formed with piperine and CYP3A4 was shown to be the most stable of all, with a binding energy of -8.60 kcal/mol. This explains the related mechanism of drug-herb interaction, since the better anchoring of piperine in the active site of CYP3A4 can hinder the drug-enzyme interaction, thereby increasing the bioavailability of the drugs studied.

Análise de fármacos em águas por SPE-UPLC-ESI-MS/MS

A method was developed for the analysis of 31 pharmaceutical compounds in Lisbon's drinking water system, using solid-phase extraction (SPE) and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). The method was validated through estimation of the linearity range, method detection and quantification limits, matrix effects, precision and accuracy. The method detection and quantification limit ranges were 0.009-10 and 0.03-33 ng/L, respectively. Analytes were quantified in water samples collected from the EPAL (Empresa Portuguesa das Águas Livres S.A.) supply system. Carbamazepine, atenolol, sulfadiazine, sulfamethazine, sulfapyridine, sulfamethoxazole, acetaminophen, caffeine and erythromycin were quantified in the analysed samples.

Avaliação da remoção de fármacos e de desreguladores endócrinos em águas de abastecimento por clarificação em escala de bancada

In this work, the efficiency of clarification treatment (coagulation, flocculation and sedimentation) with polyaluminum chloride (PAC) and aluminum sulfate (SA) as coagulants was evaluated in the removal of 7 microcontaminants (diclofenac - DCF, sulfamethoxazole - SMX, ethinylestradiol - EE2, bisphenol-A - BPA, estradiol - E2, estrone - E1 and estriol - E3) in water of low and high turbidity. The clarification treatment led to poor removal rates (40% at most) for all microcontaminants except SMX which exhibited intermediate removal efficiency (67 to 70%). Overall, PAC application yielded better performance compared to SA.