Evaluation of the bioequivalence of capsules containing 150 mg of fluconazole / Avaliação da bioequivalência de formulações do mercado nacional contendo fluconazol

AUTOR(ES)
DATA DE PUBLICAÇÃO

1999

RESUMO

Fluconazole is an antifungal agent widely used in the prevention and treatment of invasive fungal infections. Many brazilian pharmaceutical industries manufacture capsules containing 150 mg of fluconazole. As such products contain the same amount of the same therapeutically active ingredient in the same dosage form, they are considered to be interchangeable, indeed no bioequivalence study have been conducted to assess this. The present study was designed to perform in vitro (dissolution kinetics) and in vivo (bioequivalence) biopharmaceutical evaluation of two commercial products available in Brazil: Zoltec® 150 mg (Pfizer) as the reference product (R) and Flunazol® 150 mg (Sintofarma) as the test product (T). There is no official dissolution method for fluconazole dosage forms so initially a methos was developed and standardized for the evaluation of dissolution kinetics of fluconazole capsules. Dissolution kinetics for samples from two batches of R and two batches of T was analysed through ks (dissolution rate constant) and t85% (time for dissolution of 85% of the drug in the dosage form), obtained from dissolution profiles. Results showed ks values of 0,1079 min-1 and 0,1377 min-1 for the two tested batches of R and 0,5421 min-1 for both tested batches of T, and t85% values between 15,09 min and 20,06 min for R and between 5,64 min and 6,02 min for T. Bioequivalence assay was crossover and randomized. Blood samples were collected throughout a 96 hours period after administration of R and T to 28 fasting volunteers. A simple, accurate, precise and sensitive high-performance liquid chromatographic (HPLC) method without internal standard, and ultraviolet detection at 210 nm, was developed and validated for quantification of fluconazole im plasma samples after liquid-liquid extraction. Bioequivalence was assessed through pharmacokinetic parameters Cmax (peak plasma concentration), tmax (time to reach Cmax) and AUCT (área under the “plasma concentration vs time” curve) for R and T. Results were submitted to statistical analysis according to the FDA-USA and 90% confidence intervals (90% C.I.) were calculated for T and R Cmax ratios and T and R AUCT ratios. Average Cmax, tmax and AUCT values for R and T were, respectively: 3,64 mg/L and 3,75 mg/L; 2,96 h and 2,79 h; 153,33 mgh/L and 154,45 mgh/L. 90% C.I. for Cmax and AUCT were, respectively, 101,06% - 105,45% and 97,96% - 103,36%. Results show that R and T are bioequivalent and can be administered in an interchangeable way, without any prejudice of therapeutic effect.

ASSUNTO(S)

plasma capsule hplc bioequivalência cápsula fluconazol fluconazole clae bioequivalence plasma

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