RESUMO
Carvedilol is an antihypertensive drug with non-selective blockade (moderate selectivity for ß1 and ß2 adrenoceptors) and vasodilating properties due to α receptor blockade. Its molecule has one chiral centre; therefore, the drug has two enantiomers. Furthermore, it presents different polymorphs depending on the synthesis route and crystallization procedure. Carvedilol is a weak base that is substantially insoluble in water, acidic solutions, and gastric and intestinal fluids; it is classified as a Class II drug in the Biopharmaceutical Classification System. The solubility of carvedilol varies according to the solvent pH. This study aimed to evaluate and correlate the physicochemical and processability properties of carvedilol. Samples of the active ingredient from three different manufacturers were characterized according to their flowability, particle size and apparent density and using microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy, intrinsic dissolution and powder dissolution tests. It was determined that the tested samples presented the same polymorphic form, did not present good flowability, and presented different particle size distributions. The tests to evaluate flowability and compressibility were shown to be discriminative, and slight differences among the samples were noted.
Assuntos
Carbazóis/química , Propanolaminas/química , Varredura Diferencial de Calorimetria/métodos , Carvedilol , Química Farmacêutica/métodos , Cristalização , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Difração de Pó/métodos , Pós/química , Solubilidade , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tecnologia Farmacêutica/métodos , Difração de Raios X/métodosRESUMO
Co-crystals are multicomponent substances designed by the addition of two or more different molecules in a same crystallographic pattern, in which it differs from the crystallographic motif of its co-formers. The addition of highly soluble molecules, like nicotinamide, in the crystallographic pattern of ibuprofen enhances its solubility more than 7.5 times, improving the properties of this widely used drug. Several analytical solid state techniques are used to characterize the ibuprofen-nicotinamide co-crystal, being the most used: mid-infrared (ATR-FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRPD) and Raman spectroscopy. These analytical solid state techniques were evaluated to quantify a mixture of ibuprofen-nicotinamide co-crystal and its co-formers in order to develop a calibration model to evaluate the co-crystal purity after its synthesis. Raman spectroscopy showed better result than all other techniques with a combination of multivariate calibration tools, presenting lower values of calibration and prediction errors. The partial least squares regression model gave a mean error lower than 5% for all components presented in the mixture. DSC and mid-infrared spectroscopy proved to be insufficient for quantification of the ternary mixture. XRPD presented good results for quantification of the co-formers, ibuprofen and nicotinamide, but fair results for the co-crystal. This is the first report of quantification of ibuprofen-nicotinamide co-crystal, among its co-formers. The quantification is of great importance to determine the yield of the co-crystallization reactions and the purity of the product obtained.
Assuntos
Ibuprofeno/química , Niacinamida/química , Calibragem , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Cristalização/métodos , Cristalografia por Raios X/métodos , Análise dos Mínimos Quadrados , Difração de Pó/métodos , Solubilidade , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Análise Espectral Raman/métodos , Tecnologia Farmacêutica/métodos , Difração de Raios X/métodosRESUMO
A new beamline, fully dedicated to X-ray powder diffraction (XPD) measurements, has been installed after the exit port B of the bending magnet D10 at the Brazilian Synchrotron Light Laboratory (LNLS) and commissioned. The technical characteristics of the beamline are described and some performance indicators are listed, such as the incoming photon flux and the angular/energy resolutions obtainable under typical experimental conditions. The results of a Rietveld refinement for a standard sample of Y2O3 using high-resolution data are shown. The refined parameters match those found in the literature, within experimental error. High-resolution XPD measurements on Ba2FeReO6 demonstrate a slight departure from the ideal cubic double-perovskite structure at low temperatures, not detected by previous powder diffraction experiments. The onset of the structural transition coincides with the ferrimagnetic ordering temperature, Tc approximately equal to 315 K. Subtle structural features, such as those reported here for Ba2FeReO6, as well as the determination and/or refinement of complex crystal structures in polycrystalline samples are ideal candidate problems to be investigated on this beamline.
Assuntos
Compostos de Cálcio/análise , Compostos de Cálcio/química , Óxidos/análise , Óxidos/química , Difração de Pó/instrumentação , Refratometria/instrumentação , Síncrotrons/instrumentação , Titânio/análise , Titânio/química , Difração de Raios X/instrumentação , Brasil , Desenho de Equipamento , Análise de Falha de Equipamento , Conformação Molecular , Difração de Pó/métodos , Refratometria/métodos , Difração de Raios X/métodosRESUMO
The crystal structure of lithium benzilate hemihydrate (C(14)H(11)O(3)(-)Li(+).0.5H(2)O) was solved from synchrotron powder diffraction data. This compound crystallizes in the monoclinic space group P2(1)/a. The structure was solved via the direct space search for two benzilate fragments using the simulated-annealing program DASH, localization of the lithium ions and water molecule from a difference Fourier map, and a restrained Rietveld refinement (R(wp) = 0.0687). The structure is a coordination polymer of [Li(2)(C(14)H(11)O(3))(2).H(2)O](2) tetramers building helical fourfold one-dimensional channels parallel to [010]. Inside the channels the tetrahedral coordination spheres of the lithium ions contain hydroxyl and carbonyl groups, and water molecules. The water molecule functions as the cohesive entity forming extended hydrogen-bonded chains running along [010], and bifurcated donor hydrogen bonds with the two nearest carboxylates. At the outer edge of the channels, weaker intermolecular C-H.Ph hydrogen bonds along [100] and [001] contribute to the supramolecular aggregation of the structure.