2 research outputs found
New sustained release of Zidovudine Matrix tablets â cytotoxicity toward Caco-2 cells
Objective: The aim of this study was to adjust the zidovudine (AZT) release from solid tablets to an ideal profile, by
developing matrices comprising swellable polymers with nonswellable ones.
Methods: Directly compressed matrices comprised different ratios of hydroxypropylmethylcellulose K15M and
K100M, ethylcellulose, and methacrylic acid (EudragitÂź RS PO and EudragitÂź RL PO) were prepared. Technological
characterization and evaluation of the in vitro release behavior were carried out. Cell density and viability following
drug exposure were evaluated by the SRB method, for the Caco-2 line, while cell morphology was assessed upon
Trypan blue staining.
Results: A specific formulation containing 5% of each excipient â HPMC K15M, HPMC K100M, EudragitÂź RS PO, and
EudragitÂź RL PO â was found to yield the best release profile. Application of the KorsmeyerâPeppas model to the
dissolution profile evidenced that a non-Fickian (anomalous) transport is involved in the drug release. Regarding
the influence of the tabletsâ composition on the drugâs cytotoxic effect toward the Caco-2 cell line, a reduction of cell
biomass (0â15%) was verified for the distinct AZT formulations tested, F19 having displayed the highest cytotoxicity,
after 24 and 48 h of incubation. Additionally, a high reversibility of the AZT effect was observed.
Conclusions: The results showed that the simultaneous application of both hydrophilic and hydrophobic polymers
can modulate the drug release process, leading to an improved efficacy and patient compliance. All AZT formulations
studied were found to be cytotoxic against Caco-2 cells, F19 being the most effective one.J.V.S. acknowledges
PhD fellowship from the Programme AlÎČan, the
European Union Programme of High Level Scholarships
for Latin America (scholarship no. E06D100103BR)