Paulo Roberto da Silva Ribeiro

Synthesis of a Glibenclamide Cocrystal: Full Spectroscopic and Thermal Characterization

A cocrystal of glibenclamide, an antidiabetic drug classified as type II compound according to the Biopharmaceutics Classification System, has been synthesized using tromethamine as coformer in 1:1 molar ratio, by slow solvent evaporation cocrystalization. The cocrystal obtained was characterized by X-ray powder diffraction, differential scanning calorimetry, Raman, mid infrared, and near-infrared spectroscopy. The results consistently show the formation of a cocrystal between active pharmaceutical ingredients and conformer with the synthons corresponding to hydrogen bonding between hydrogen in amines of tromethamine and carbonyl and sulfonyl groups in glibenclamide.

Statistical process control of cocrystallization processes: A comparison between OPLS and PLS

Orthogonal partial least squares regression (OPLS) is being increasingly adopted as an alternative to partial least squares (PLS) regression due to the better generalization that can be achieved. Particularly in multivariate batch statistical process control (BSPC), the use of OPLS for estimating nominal trajectories is advantageous. In OPLS, the nominal process trajectories are expected to be captured in a single predictive principal component while uncorrelated variations are filtered out to orthogonal principal components. In theory, OPLS will yield a better estimation of the Hotellings T2 statistic and corresponding control limits thus lowering the number of false positives and false negatives when assessing the process disturbances. Although OPLS advantages have been demonstrated in the context of regression, its use on BSPC was seldom reported. This study proposes an OPLS-based approach for BSPC of a cocrystallization process between hydrochlorothiazide and p-aminobenzoic acid monitored on-line with near infrared spectroscopy and compares the fault detection performance with the same approach based on PLS. A series of cocrystallization batches with imposed disturbances were used to test the ability to detect abnormal situations by OPLS and PLS-based BSPC methods. Results demonstrated that OPLS was generally superior in terms of sensibility and specificity in most situations. In some abnormal batches, it was found that the imposed disturbances were only detected with OPLS.

Near infrared spectroscopy to monitor drug release in-situ during dissolution tests.

Dissolution tests can be used to demonstrate suitable in vivo drug release through in vivo/in vitro correlations. This work explores the possibility of using near infrared spectroscopy (NIRS) to monitor in-situ dissolution tests. It aims at expanding surrogate methods in quality control of drug products. Laboratory designed tablets of an immediate-release formulation containing folic acid and four excipients were used as case study. The dissolution tests were performed on a 1L vessel filled with 500ml of Milli-Q water with a rotating paddle apparatus (apparatus 2, Ph. Eur.) at 50rpm and 37±0.5°C. Near infrared (NIR) spectra were acquired in-situ with a transflectance probe connected to a Fourier-transform near infrared spectrometer. NIR spectra were regressed against folic acid concentration by partial least squares (PLS) regression. Folic acid concentrations during dissolution tests were obtained by periodically sampling the dissolution vessel and resourcing to an UV method. The proposed real-time NIR method was tested on a validation run yielding a root mean squared error of 0.25μgml-1 (0.16μgml-1 for the calibration runs) and a R2 of 0.93 (0.95 for the calibration runs). The results suggest that NIRS is a suitable analytical technique for monitoring in-situ dissolution tests.

Operational characteristics of microgrids with electric vehicles

Microgrids are the basic building cells of a smart grid. They are assumed to be established at the low voltage distribution level, where distributed energy sources, storage devices, controllable loads, and electric vehicles are integrated and need to be properly managed. The microgrid cell is a very flexible system that can be operated connected to the main power network or autonomously, in a controlled and coordinated way. When operating in islanded mode, the MG relies on local energy storage to ensure the balance between generations and loads. However, when operating isolated from the main grid, the MG is more sensitive to power quality issues such as voltage unbalance, caused by the connection of single-phase loads and sources. In order to improve the MG emergency operation conditions, the EV should be envisaged as an active and flexible entity, providing to the MG additional distributed load or storage capacity under the vehicle-to-grid (V2G) concept. This chapter reviews the MG architecture considering EV and focuses on the impact of their active participation on the MG frequency regulation in emergency conditions (namely in islanding operating mode). Voltage unbalance issues during MG autonomous operation and the need for adopting voltage balancing mechanisms in specific power electronic interfaces are also discussed.

Development and validation of a simple spectrophotometric method for the determination of methyldopa in both bulk and marketed dosage formulations

Desenvolveu-se metodo espectrofotometrico simples, preciso, sensivel, rapido, especifico e economico para a determinacao do teor de metildopa (MTD) em materia-prima e em formulacoes farmaceuticas. O metodo proposto baseia-se na formacao de um produto colorido resultante da reacao de nitrosacao da MTD com nitrito de sodio em meio acido. A especie resultante (nitroso derivado) reage com hidroxido de sodio e e convertida a um composto mais estavel de cor amarela. Este produto exibiu maximo de absorcao a 430 nm. A lei de Beer foi obedecida na faixa de concentracao de 6,37 a 82,81 μg mL-1 de MTD com excelente coeficiente de determinacao (R 2 = 0,9998). Nao se observou interferencia de excipientes comumente encontrados em formulacoes farmaceuticas comerciais. Os resultados demonstraram que o metodo proposto apresenta simplicidade, excelentes precisao e exatidao e pode ser aplicado para a determinacao de MTD na sua forma pura e em preparacoes farmaceuticas. Os resultados analiticos obtidos pelo metodo proposto estao de acordo com aqueles obtidos pelo metodo oficial descrito na Farmacopeia Brasileira, a um nivel de confianca de 95%.

Avaliação da qualidade de plantas medicinais comercializadas no Município de Imperatriz – MA

O uso de produtos fitoterapicos e a comercializacao indiscriminada de especies vegetais inadequadas para o uso medicinal associada as frequentes adulteracoes, contaminacoes e falsificacoes interferem na saude e seguranca do consumidor. Visando o controle de materias-primas amplamente consumidas no Municipio de Imperatriz – MA e as suas importantes atividades biologicas avaliou-se a qualidade dos fitoterapicos Carqueja ( Baccharis trimerae herbae) , a Calendula ( Calendula officinalis ), Sene ( Senna alexandrina P.Miller ) e a Cascara sagrada ( Rhamnus purshiana ). As amostras de carqueja apresentaram valores medios de teor de umidade de 9,8% e impureza de 24,6% superiores ao permitido pela legislacao e teor de oleo essencial apenas em 0,25%. A Calendula apresentou 0,4% de teor de oleo essencial e indice de saponinas de 142,9. A Cascara sagrada apresentou indices satisfatorios de antraquinonas, O-heterosideos hidroxiantracenicos e os C-heterosideos hidroxiantracenicos. Constatou-se a presenca de senosideo C, senosideo B e 11,43% de cinzas totais e 1,7% de cinzas insoluveis, nao ultrapassando o valor maximo de 12% (para cinzas totais) e 3% (para cinzas insoluveis) nas amostras de Sene.

Development and application of a portable instrument for drugs analysis in pharmaceutical preparations

This article describes the application and performance of an inexpensive, simple and portable device for colorimetric quantitative determination of drugs in pharmaceutical preparations. The sensor is a light detector resistor (LDR) incorporated into a black PTFE cell and coupled to a low-cost multimeter (Ohmmeter). Quantitative studies were performed with captopril/p-chloranil/H2O2 and methyldopa/ammonium molybdate systems. Calibration curves were obtained by plotting the electrical resistance of the LDR against the concentration of the colored species in the ranges 1.84 × 10-4 to 1.29 × 10-3mol L-1 and 5.04 × 10-4 to 2.52 × 10-3 mol L-1 for captopril/p-chloranil/H2O2 and methyldopa/ammonium molybdate systems, respectively, exhibiting good coefficients of determination. Statistical analysis of the results obtained showed no significant difference between the proposed methodologies and the official reported methods, as evidenced by the t-test and variance ratio at a 95% confidence level. The results of this study demonstrate the applicability of the instrument for simple, accurate, precise, fast,in situ and low-cost colorimetric analysis of drugs in pharmaceutical products.