Avaliação das características físico-químicas, farmacocinéticas e da biodisponibilidade relativa de comprimidos contendo associação de lamivudina 150 mg e zidovudina 300 mg / Assessment of physicochemical, pharmacokinetic and relative bioavailability characteristics of tablets containing combination lamivudine 150 mg and zidovudine 300 mg

RESUMO

Lamivudina (3TC) e zidovudina (ZDV) são inibidores nucleosídeos da transcriptase reversa utilizados na terapêutica anti-HIV. Para avaliar a equivalência farmacêutica entre um medicamento teste contendo esta associação e o referência, foi desenvolvido um método para determinação cromatográfica simultânea de 3TC e ZDV em comprimidos. O método empregou coluna C8 Shim-pack® (150 x 4,6 mm, 5 um), pré-coluna C18 Phenomenex® (50 x 4,6 mm 5 um), água e metanol 6040 (vv) como fase móvel e detecção a 266nm. Este mostrou-se específico, com linearidade entre 45 a 5000 ng/mL, precisão demonstrada por CV por cento inferior a 5 por cento, exatidão entre 90,0 e 110,0 por cento com recuperação superior a 90 por cento para ambos os fármacos...

ABSTRACT

Lamivudine (3TC) and zidovudine (ZDV) are the nucleoside reverse transcriptase inhibitors, They are used in combinations of antiretroviral therapy. The switchability between one test product and reference could be proved if they are pharmaceutically equivalents and bioequivalents. This research beginning with development and validation of chromatographic method to 3TC and ZDV simultaneous determination in tablet. The HPLC system were used to assay and 266nm wavelength ultraviolet detector. Separation was performed using a C8 column (150 x 4,6 mm, 5 µm) Shim-pack®protected by a C18 column (50 x 4,6 mm, 5 µm) Phenomenex®. The mobile phase is composed of water and methanol 6040 (vv). This method was successfully applied to simultaneous determination to 3TC and ZDV without interference. It was validated over the range of 45 a 5000 ng/mL for both drugs with accurate from 90 to 110% and precision with variation lower than 5%. Extraction recoveries of the analytes were higher than 90%. The mean dissolution data about 3TC and ZDV were above than 85% in 30 minutes of dissolution test. The relative bioavailability between Biovir® (brand-name product) and Lamivudina + Zidovudina 150 + 300 mg (test product), was conducted for one direct quantitative, open and crossover study. The serial plasma sample of 3TC and ZDV collected after oral administration of brand-name product and test product, were analyzed using a validated high-performance liquid chromatography assay with UV detection in wavelength of 270 nm. The double liquid-liquid extraction was realized with additions of amonio acetat. A CLC-C8 (M) column (150 x 4,6 mm 5 µm) Shim-pack®and C18 column (50 x 4,6mm 5 µm) Phenomenex®, was eluted with two mobile phase in a linear gradient system at a flow-rate...