New sustained release of Zidovudine Matrix tablets − cytotoxicity toward Caco-2 cells

Abstract

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 (Eudragit® RS PO and Eudragit® 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 − HPMC K15M, HPMC K100M, Eudragit® RS PO, and Eudragit® RL PO − was found to yield the best release profile. Application of the Korsmeyer-Peppas model to the dissolution profile evidenced that a non-Fickian (anomalous) transport is involved in the drug release. Regarding the influence of the tablets' composition on the drug's cytotoxic effect toward the Caco-2 cell line, a reduction of cell biomass (0-15%) 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.

Relaxation versus diffusion on the diclofenac sodium release from matrix tablets containing hydroxypropylmethylcellulose and/or chitosan

“…Raman spectroscopy has been widely applied to evaluate drug-excipient compatibility in pre-formulation studies (Marques et al, 2002;Vueba et al, 2006Vueba et al, , 2008Santos et al, 2012), and was presently used to detect solid-state interactions among DS and the excipients considered in the tested formulations. A 1:1 (w:w) drug:excipient ratio was chosen, as this is known to take advantage of the probability of occurrence intermolecular interactions.…”

Utility of Different Lipids and Effect of Soya Lecithin on Sustained Delivery of Zidovudine via Biodegradable Solid Lipid Microparticles: Formulation and in-vitro Characterization

“…Formulation of matrix tablets of AZT using different combinations of rate controlling polymers was frequently investigated where the drug diffused through the matrix in a controlled fashion. [14][15][16] Alginate microspheres of AZT was prepared by ionotropic gelation technique which were coated with drug release modifiers to prolong the release over 12 hr. 6 Ethyl cellulose microspheres of AZT were prepared using solvent evaporation technique to sustain the release of drug over 24 hr.…”

Formulation and Design of Extended Release Matrix Tablets of Zidovudine Hydrochloride: A Study on Effect of Various Grades of Ethocel and HPMC

“…This drug has more contribution towards prevention of HIV infection from infected mother to newborn. However serious side effects also marked in certain cases such as lactic acidosis, myopathy, weakness, immune reconstitution inflammatory syndrome, blood anemia, unusual breathing, dark color urine, neutropenia, muscle pain etc [6]. Such above mentioned cases always associated in chronic administration of dosage.…”