Utilización de la Espectroscopia NIR en el Control Analítico de la Industria Farmacéutica. Desarrollos iniciales en PAT

Abstract

The application of NIR Spectroscopy to the determination of interest parameters in the pharmaceutical industry has been studied, with the intention of proposing new, faster and effective methodologies than the conventional methods. The studies develop a wide variety of methods that cover the determination of active principles in process samples or finished products, also physical properties of these same samples, in different matrices and concentration levels. New NIR methods for the determination of the five active principles in a formulation, constituted by a granulated solid, have been developed, with concentrations between 6% up to 0.04%; this method demonstrates the capacity of the technique in multiple determinations and its remarkable sensitivity. Another example of the capacity of the technique constitutes the determination of active principles and the preservants of a pharmaceutical hydrogel that presents a strong absorption of the matrix and low concentration of the preservants. Also, methods for the determination of the active principle in intact tablets have been developed, which allows the study of content uniformity in unit doses of the preparation. The developed methods have been validated following the guides ICH and EMEA which allow their application for the analytical quality control of production processes. Another aspect of the study is the establishment of methods to determine physical parameters of finished products, as compaction pressure and dissolution test, which are both closely related. The NIR method allows the determination of the complete dissolution profile of a tablet from its spectrum, which provides very fast information (less than 1 second) that by the conventional method needs more than 1 hour. The determination of the compaction pressure of tablets has given rise to a new method of determination of active principles in individual tablets, using solely laboratory tablets as the calibration set, which allows obtaining simpler and robust models than NIR methods developed until the moment. The application of new chemometric methods for the treatment of spectra (MCR-ALS) has allowed to identify polymorphic changes (from crystalline to amorphous form) that take place during the process of wet granulation, which is a frequent stage of the pharmaceutical process. This polymorphic transformation can have influence in the bioavailability of the active principle. The memory also includes a chapter of a book, by order of the publisher, on the application of the NIR in the pharmaceutical field and that gathers the main contributions made in this field, whose interest and development are in continuous growth.