Desenvolvimento de método analítico para análise simultânea do ibuprofeno e carvacrol em sistemas nanoemulsionados por UPLC

Abstract

Advances in nanotechnology have improved the pharmaceutical industry, allowing the development of more effective therapeutic systems with lower toxicity and adverse effects. Nanoemulsions (NEs) stand out for their high kinetic stability, improving the bioavailability of active compounds and increasing the permeability of substances with low solubility. Thus, the present study aimed to develop a nanoemulsion containing ibuprofen (PPI) and carvacrol (CRV) and validate a method for quantification by UPLC. In this sense, the NEs were prepared by the high-energy method using a sonicator. For the nanoemulsion containing PPI+CRV, three PPI formulations containing 50mg, 100mg and 200mg were prepared. Chromatographic analyses were performed using a mobile phase containing a mixture of acetonitrile:water acidified at 0.1% with formic acid (60/40; v/v), with a flow rate of 0.7 mL.min-1 and detection at 230 nm. The method was validated according to the parameters of selectivity, linearity, limits of detection (LOD) and quantification (LOQ), inter/intra-day precision, accuracy and robustness, as well as analyses in PDI, PZ and droplet size. The method proved to be selective and has a distinction in the retention time of CRV (9.2 min) and IBP (11.02 min). Linearity was demonstrated in the IBP and CRV concentration range of 50 to 100 μg/mL and 100 to 200 μg/mL (r² = 0.999 and r² = 0.998), respectively, meeting resolution RE no. 166. The limits of detection and quantification for PAI and CRV were 3.54 and 5.19 μg/mL, 8.64 and 12.81 μg/mL, respectively. The relative standard deviation (RSD) values for intraday and interday precision were less than 5%, and the average recovery rate was 94.85% at a concentration of 10 mg/mL for IBP and an average recovery rate of 88.57% at a concentration of 30 mg/mL for CRV, demonstrating that the method was capable of quantifying IBP and CRV samples present in the nanoemulsion. The nanoemulsions presented an average droplet size between 143 and 376.5 nm, with PDI close to 0.3 and negative zeta potential. After 60 days of formulation, the nanoemulsions showed macroscopic results, preserving the milky appearance without creaming or phase separation. It is concluded, therefore, that the present work presented overwhelming results that proved the reliability of the method, showing that it is reproducible, meeting the criteria of both ANVISA and INMETRO, revealing new advances in the field of research, with potential for the development of safer and more effective therapies. In addition, the nanoemulsion containing IBP and CRV showed promise, standing out for its stability and ability to maintain the properties of the active compounds over time.