Desenvolvimento de metodologia analítica por uflc, estudos de estabilidade e avaliação tecnológica de comprimidos de sildenafila

Abstract

Sildenafil is the first choice pharmaceutical product for erectile dysfunction treatment and commercially available in tablets dosage form. Nowadays, Sildenafil is among the largest selling pharmaceutical products in the worldwide marketing. For this reason, is also among the most falsified and/or smuggled in the world. The development of analytical techniques that aim to evaluate pharmaceutical products’ quality, as well as those that aim forensic samples, are extremely valuable, once they are resources for quality guaranteed pharmaceutical products availability. Thus, our present study aimed to develop and validate a stability-indicative analytical method by UFLC, in order to quantify Sildenafil in tablets. Photolytic degradation’s kinetics and biological safety of Sildenafil’s photoproducts were evaluated. Additionally, Sildenafil tablets that were suspect of falsification (conceded by Regional Superintendence of Federal Police), were evaluated according to quality criteria previously established by international compendiums, being them: (a) mechanical resistance, (b) disintegration, (c) dissolution, (d) assay, (e) chemical profile by infrared spectroscopy, and (f) physical profile. The results were evaluated by control-process statistical and multivariate analysis. The following conditions were established for UFLC method: acetonitrile:triethylamine (60:40, v:v) as mobile phase, flux at 0.7mL.min-1, C18 column (100mm x 4,6mm x 5μm), 50°C, pH 4.0 and 290 nm. Proposed method was validated following ICH’s guidance, and showed specificity, linearity, precision, accuracy, and robustness. Biological safety was determined by the following assays: (a) Trypan Blue, (b) Micronucleus, and (c) Comet assay. The intact molecule, as well as its photoproducts showed cytotoxicity even no mutagenicity or genotoxicity was detected. Finally, tablets (suspected of falsification) had no quality deviation and multivariate analysis (Hierarchical Component Analysis) applied in physical profile showed adequate for sample’s classification.