title: 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.
authors.affiliation: Unidade de I&D Química-Física Molecular, Department of Chemistry, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
authors.forename: Jucimary V
authors.initials: JV
authors.lastname: Santos
authors.forename: Maria Eugénia T
authors.initials: ME
authors.lastname: Pina
authors.forename: M Paula M
authors.initials: MP
authors.lastname: Marques
authors.forename: Luís A E Batista
authors.initials: LA
authors.lastname: de Carvalho
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D006801:Humans; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013607:Tablets; D015215:Zidovudine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; D013607:Tablets; C038300:methylmethacrylate-methacrylic acid copolymer; D065347:Hypromellose Derivatives; D015215:Zidovudine; D008747:Methylcellulose