Caracterização e quantificação de Pamoato de Pirantel em formulações por ressonância magnética nuclear de sólidos

Abstract

The large global production of pharmaceutical ingredients and the increase in adulteration of commercial formulations requires the generation of new versatile methodologies for characterization and quantification. In this dissertation, a simple methodology for quantifying pyrantel pamoate (PdP), an essential medicine according to WHO, by solid state NMR (NMRq) was developed and validated as an alternative for the analysis of IFA content in commercial formulations. For this purpose, initially a PdP reference standard from the United States Pharmacopoeia was characterized with the techniques of X-ray diffraction, thermal analysis, infrared, 1H and 13C 1D and 2D NMR and 13C CP-MAS NMR, and it was confirmed to be suitable as reference for the validation step and for the characterization of samples containing PdP. After, seven commercial PdP formulations were characterized with the same solid techniques, which showed signs and intensities corresponding to those of the standard. For NMR quantification (qNMR) the method was developed by establishing the acquisition parameters optimized for the PdP: delay time of 62 s, contact time of 3200 μs and rotation frequency of 12 kHz. The calibration curve showed a high regression value (R2 = 0.995). For validation, selectivity, range and linearity, accuracy, intermediate precision and repeatability, robustness and limits of detection and quantification were evaluated. The results obtained met the requirements determined by ANVISA in Brazil, INS-INVIMA in Colombia and ICH as a general international standard. For the evaluation of the developed method, a comparison was made with another previously validated method using UV-Vis spectrometry, and congruent results were found between the two methods. The quantification performed in each of the seven commercial formulations with the methodology validated by 13C CP-MAS NMR allowed to identify that all presented the content of IFA (PdP) supplied by the manufacturers in the packaging, and, therefore, in these cases the products were not adulterated. With this work it was verified the efficacy, versatility and applicability for quantitative studies of drugs by 13C solid state NMR.