Estudos de degradação forçada de fármacos fluoroquinolínicos assistida por irradiação micro-ondas

Abstract

Forced degradation studies are important to determine the stability of a drug, elucidate its main routes of degradation, and to monitor its degradation products, which can generate therapeutic inefficacy or exhibit a toxicity profile. Some guides suggests that such studies must be conducted by conditions of extreme stress such as acids or bases (hydrolysis), hydrogen peroxide (oxidative stress), temperature and exposure to light. However, such studies are costly and require a long time and large amounts of solvents. Heating by microwave irradiation in different areas of chemistry is already an established technology. Recently, forced degradation studies have been used microwave as a heating source in modern reactors that control temperature, power, pressure and agitation, making this technology viable in studies of stress. The aim of this study was to design and validate a method of forced degradation assisted by microwave irradiation in fluorinated quinolones (levofloxacin and norfloxacin) alongside conventional stress study and compare them. For this purpose, solutions of levofloxacin and norfloxacin were subjected to usual forced degradation under influence of various stress agents and under microwave irradiation in sealed glass tubes and stirring conditions, temperatures up to 120 ° C and a maximum pressure of 100 psi. Both drugs were degraded between 10 and 30%, with equivalent chromatographic profile of peaks and the presence of possible degradation products with areas and retention times very similar. For levofloxacin, stress solution of 0.3% (v/v) hydrogen peroxide at room temperature for 720 minutes produced a 26% of degradation and the same solution in an oven at 60 ° C for 60 minutes, degraded 27%. This solution in exposure to a microwave irradiation at 100 ° C for 20 minutes and 120 ° C for 5 minutes degraded, respectively, 28% and 25%. For norfloxacin, applying 0.1 mol L-1 sodium hydroxide at room temperature for 1440 minutes, 7% of degradation was observed and in an oven at 60 ° C for 180 minutes, 12% of degradation. On exposure to microwave at 100 ° C for 20 minutes and 120 ° C for 5 minutes was obtained degradation, respectively, 11% and 10%. For the conditions that generate degradation were formed similar amounts of degradation products for both drugs, stating the equivalence between the use of conventional and forced degradation by microwave irradiation (with temperature control, agitation and pressure), but with reduced significant time to the new technique, since it enables the temperature rise above the boiling point of the solvent.