Estudio de la influencia de parámetros físicos en la construcción de modelos de calibración en la espectroscopia en el infrarrojo cercano

Laburpena

In the last years there has been an increase in the use of near infrared spectroscopy, due to its multiple advantages: it is a non-invasive and non-destructive technique, it requires very little or no sample preparation, the ability to provide measurements and results in a highly expeditious manner, the low cost of analysis, an absence of reagents; as well as the possibility of making simultaneous determination of physical and chemical parameters. Nonetheless, the characteristic of the NIR signal requires the application of multivariate methods to obtain the desired information contained in the spectrum. The spectral variability produced by the insufficient control of physical parameters, gives rise to complex models of calibration as well as a poorer predictive capacity. In an industrial process experimental conditions can not always be strictly controlled and variations of the physical conditions of the system (temperature, pressure, moisture, etc.) often take place. The different arrangement from molecules in a crystalline structure gives rise to the polymorphism and this property complicate the models of calibration of samples in which this property is present. In the pharmaceutical industry is very common that active principles can exist in two or more different crystalline forms (polymorphs). We have taken advantage of these differences for the characterization and determination of different polymorphs of a substance. One of the objectives of this thesis is to develop new methodologies of analysis for the identification and characterization of polymorphs of azithromycin by means of NIR spectroscopy. Models of calibration were developed based on the algorithm of partial least-square (PLS) regression for the determination of a polymorphic form in the presence of another and were validated for their application in the pharmaceutical industry. In addition, a study of stability under high temperature and moisture conditions was car