Teste de dissolução biorrelevante aplicado à predição da bioequivalência de comprimidos de liberação imediata empregando Aparato 4 (USP) para facilitar a CIVIV

Abstract

The USP- 4 dissolution apparatus have been often reported as an alternative method for in vivo in vitro correlations (IVIVC) in order to provide biowaivers. Accordingly, maintenance of sink and flow through cell conditions as well as convenience of exchanging dissolution medium are some of the advantages of such apparatus. Therefore, the achievement of biomimetic gastrointestinal tract (GIT) conditions is favored over the classic apparatus (paddle and basket). In this work, the USP- 4 apparatus was employed in order to get biorelevant dissolution methods with strong IVIVC. Dissolution profiles were achieved for the test and reference formulations containing four compounds of class II of Biopharmaceutical Classification System (BCS) – diclofenac potassium, ibuprofen, nifedipine and nimesulide, and three BCS III compounds - captopril, losartan potassium and ranitidine. Drug plasma concentrations were provided by previous bioequivalence studies (Instituto de Ciências Farmacêuticas - ICF/GO database) from human volunteers (n ≥ 24), run with the same dissolution batches. Such values were submitted to deconvolution process as defined by Wagner-Nelson method. Level C IVIVC were set by linear regression analysis of fraction dissolved (Fdiss) versus fraction absorbed (Fa). Correlation coefficient was adjusted using mutual time points of Fdiss and Fa generated in common. Obtained data showed strong correlation 30, 90, 120, 180, 240, and 360 min, for BCS II (0,81 ≤ R ≤ 0,99) compounds opposing to BCS III which IVIVC could not be found.