Aplicação do infravermelho próximo aliada à calibração multivariada para construção da tecnologia analítica em processo na produção da olanzapina compridos revestidos

Abstract

Olanzapine is a benzodiazepine which proved efficacy in the treatment of positive and negative symptoms of schizophrenia, bipolar disorder and others psychoses. The pharmaceutical industry and analytical laboratories have focused on quality, safety and efficacy of their products, for this planning tools and monitoring are required in the production scale. The concept of Process Analytical Technology introduces innovative approaches, as improvement of process control and comprehension of carried out procedures to improve the efficiency. This study applies the near infrared spectroscopy to build the Process Analytical technology in the production of Olanzapine coated tablets, since this technique has being wide use, because it is not necessary to prepare the samples, the absence of residues produced and the analysis are fast, when compared to the reference techniques, e.g. chromatography. Previously to implementation of Process Analytical Technology some laboratory steps are required to evaluate if the technique are sensitive to the objective. To prove the theory, alternative methods were developed to compare with their references. In the Chapter 1 it was carried out the assay of the drug using high performance liquid chromatography and near infrared associated to multivariate calibration techniques (partial least square – PLS), after the spectra pre-treatment). The results obtained by the near infrared were compared to the chromatography and as response: the assay by both methods did not presented statistically significance difference. In the Chapter 2, the thesis was focused at the construction of multivariate control charts, based on Net Analytical Signal (NAS) to monitor the assay of the drug in laboratory and production samples using near infrared spectroscopy. The control charts (NAS, interferers and residuals) were built and they were promisor with high level of recognition (95 to 100%) of samples that were exactly in or out of the specified range. Lastly, at the Chapter 3 the determination of water content by near infrared associated to multivariate calibration, PCR, of Olanzapine and excipients granulate mixtures in laboratory and production samples was analyzed and compared to the reference method (Karl Fischer). The results, when NIR and Karl Fischer were compared, presented no significant statistically difference, promoting the NIR associated to multivariate calibration also works to analyze the water content into the coated olanzapine tablets. The results showed that the multivariate calibration models constructed, using the spectra obtained by the near infrared, were promisors, when compared to the reference methods. Therefore, the alternative analytical tool (near infrared spectroscopy) can be installed at production scale to monitor the drug quality at this matrix used.