Extração e purificação de fármacos anti-inflamatórios não esteroidais ciclo-oxigenase-2 seletivos

Celecoxib (CB) and lumiracoxib (LM) are potent COX-2 inhibitors widely marketed for the treatment of rheumatoid arthritis and osteoarthritis. Nevertheless, it is difficult to obtain because it are protected under patents. The aim of this work was to develop an extraction method of drugs, CB and LM, in order to obtain the drug with a purity degree appropriated for use in research projects. The developed method showed to be effective of both drugs, becoming interesting due to its low cost, easy and speed of execution, application to different dosage forms (capsules and tablets) and drugs with different physicochemical properties.

Polímeros com capacidade de reconhecimento molecular no controlo da libertação de fármacos. Parte 1: síntese e caracterização

Molecularly imprinted polymers (MIPs) consist of synthetic macromolecular matrix, obtained through molecular imprinting-based methods that show ability to selectively recognize important biological molecules and its application in the drug delivery field is under development. In the present review the main aspects related to the synthesis and characterization of MIPs are studied. The fundamental variables participating in the synthesis process, such as template molecule, functional monomers, cross-linking agents, solvents and imprinting approaches are discussed. Moreover, the main available methods for MIPs chemical and morphological characterization are presented and the importance of the obtained information is discussed.

Quimioterapia da doença de Chagas: estado da arte e perspectivas no desenvolvimento de novos fármacos

Neglected diseases are a major global cause of illness, long-term disability and death. Chagas' disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. The existing drug therapy suffers from a combination of drawbacks including poor efficacy, resistance and serious side effects. In 2009, we celebrate the 100th anniversary of the discovery of Chagas' disease, facing the challenges of developing new, safe and effective drugs for the treatment of this disease. This brief review attempts to highlight the state of the art, limitations and perspectives of Chagas' disease drug development.

Tecnologia de nanocristais em fármacos

The use of poorly water soluble molecules in pharmaceutical area has grown. Since these molecules exhibit low oral bioavailability, they are not used in intravenous administrations. Therefore, it is necessary to develop their new formulations with the aim to increase their oral bioavailabilities as to enable intravenous applications. One of the few possibilities in achieving this is a nanonization process that can produce crystals smaller than 1 μm by high pressure homogenization and without use of organic solvents. This mini-review describes technical aspects of the nanocrystal production, morphological aspects (polymorphisms), the market relevance of the nanocrystals products that are already in clinical phase or at the market, as well as, perspectives for the near future.

Metabólitos secundários de origem vegetal: uma fonte potencial de fármacos antitrombóticos

Cardiovascular diseases are responsible for the largest number of deaths among humans worldwide, including heart attacks, strokes, and thrombosis. The treatment of thrombosis is generally through the administration of anticoagulant and/or antiplatelet drugs, which have some clinical limitations. Plants synthesize a wide variety of bioactive metabolites in response to different stimuli. This review focuses on a number of molecules of vegetal origin belonging to different chemical classes, with significant anticoagulant and antiplatelet effects. Their promising antithrombotic profile confirms the potential of natural products as a source of lead molecules for drug development in the prevention and treatment of thrombosis.

Proteases de Leishmania: novos alvos para o desenvolvimento racional de fármacos

Leishmania causes tegumental and visceral diseases called leishmaniasis. Disease control is possible interrupting the transmission cycle, but HIV co-infection, chemotheraphy toxicity and lack of a vaccine are paramount difficulties. So, is necessary to study new Leishmania molecules and investigate the possibility to develop rational drugs using these molecules as targets. Leishmania express many peptidases during their life, and cysteine are the most abundant protease and many inhibitors were developed but failed to kill parasites. On the other hand, inhibitors of serine proteases killed promastigotes, indicating the possibility of these enzymes to be important targets in the development of anti-Leishmania drugs.

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.

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.