RESUMO
A nondestructive and faster methodology to quantify mechanical properties of polypropylene (PP) pellets, obtained from an industrial plant, was developed with Raman spectroscopy. Raman spectra data were obtained from several types of samples such as homopolymer PP, random ethylene-propylene copolymer, and impact ethylene-propylene copolymer. Multivariate calibration models were developed by relating the changes in the Raman spectra to mechanical properties determined by ASTM tests (Young's traction modulus, tensile strength at yield, elongation at yield on traction, and flexural modulus at 1% secant). Several strategies were evaluated to build robust models including the use of preprocessing methods (baseline correction, vector normalization, de-trending, and standard normal variate), selecting the best subset of wavelengths to model property response and discarding irrelevant variables by applying genetic algorithm (GA). Linear multivariable models were investigated such as partial least square regression (PLS) and PLS with genetic algorithm (GA-PLS) while nonlinear models were implemented with artificial neural network (ANN) preceded by GA (GA-ANN). The best multivariate calibration models were obtained when a combination of genetic algorithms and artificial neural network were used on Raman spectral data with relative standard errors (%RSE) from 0.17 to 0.41 for training and 0.42 to 0.88% validation data sets.
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Near-infrared chemical imaging (NIR-CI) spectra of lactose monohydrate tablets were acquired and the spectral slope from each pixel in the data hypercube was used to assess tablet compaction and relaxation. Tablets were prepared at compaction pressures of 100, 300, and 500 MPa using un-lubricated and magnesium stearate lubricated lactose monohydrate. Results show that NIR slope distribution is a function of applied compaction forces and magnesium stearate lubrication. The distribution of NIR slope values was studied using histograms and statistical parameters. The mean slope value yields a linear calibration curve that predicts tablet compaction pressure as a function of spectral slope. The NIR-CI slope measurements were also used to study tablet relaxation, which occurs as tablets release some of the stored energy from compression. The NIR-CI slope method provides a qualitative description of the relaxation process and provides quantitative information describing relaxation through time.
Assuntos
Espectrofotometria Infravermelho/métodos , Comprimidos/química , Tecnologia Farmacêutica/métodos , Fenômenos Químicos , Lactose/química , Lubrificação , Pressão , Ácidos Esteáricos/químicaRESUMO
A three-way calibration strategy has been used to develop a simple method for drug quantitation in intact pharmaceutical tablets. The experimental design defined for the three-way calibration gathers a large variation in drug concentration (15-85% w/w) and compaction pressure (100-500 MPa). These could be process variable ranges during the development of a pharmaceutical formulation following the quality by design (QbD) approach. When a large variation in both chemical and physical variables is defined, the traditional two-way calibration strategies, such as partial least squares (PLS), do not allow the obtaining of multivariate model with good predictive ability (nonlinear predictions and prediction error over 8% w/w). The presented strategy uses parallel factor analysis (PARAFAC) to deconvolute the spectra in scores associated with drug concentration variation, and loadings related with wavelength range and compaction range. The PARAFAC deconvolution was followed by multiple linear regression (MLR) to obtain the simple calibration model with a better predictive ability on the whole compaction pressure range (prediction error less than 1.4% w/w). The proposed three-way strategy can be easily designed and executed, obtaining a multivariate analytical method more robust than using a traditional two-way modeling technique.
Assuntos
Preparações Farmacêuticas/química , Preparações Farmacêuticas/normas , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espectroscopia de Luz Próxima ao Infravermelho/normas , Calibragem/normas , Análise Multivariada , Preparações Farmacêuticas/análise , ComprimidosRESUMO
The content uniformity of low dose products is a major concern in the development of pharmaceutical formulations. Near infrared spectroscopy may be used to support the design and optimization of potent drug manufacturing processes through the analysis of blends and tablets in a relatively short time. A strategy for the selection of concentration ranges in the development of multivariate calibration is presented, evaluating the detection and quantitation limits of the obtained multivariate models. The strategy has been applied to the determination of an active principle in pharmaceutical tablets of low concentration (0-5%, w/w), using Fourier Transform Near Infrared (FT-NIR) transmission spectroscopy. The quantitation and detection limits decreased as the upper concentration level of the calibration models was reduced. The results obtained show that the selection of concentration ranges is a critical aspect during model design. The selection of wide concentration ranges with high levels is not recommended for the determination of analytes at minor levels (<1%, w/w), even when the concentration of interest is within the range of the model.
Assuntos
Modelos Químicos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Comprimidos , Calibragem , Análise Multivariada , Sensibilidade e Especificidade , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
A near-infrared (NIR) spectroscopic method has been developed to monitor flowing pharmaceutical powders during their voiding and detect post-blending segregation. The method is capable of providing both chemical and physical information (particle size differences) on the flowing pharmaceutical powders. Particle size differences are widely recognized as the predominant driver for segregation. Pharmaceutical powders may segregate following blending as they are voided down pipes to compressing machines, increasing the variability of the drug content and dissolution of the final product tablets because of segregation. NIR diffuse reflectance spectra of pharmaceutical powders were obtained following voiding through a six-foot pipe. Spectral subtraction was used to eliminate baseline differences but maintain particle size differences. The NIR spectra indicated differences in the particle size of the flowing powder. Particle size differences were also tracked throughout the voiding of pharmaceutical powders by plotting the absorbance at 1536 nm. The method was also applied to the voiding of two layers of lactose particles with different particle sizes. The system described in this report provides an approach to study post-blending segregation in pharmaceutical powders and other relevant materials.