Polymeric drugs with prolonged sustained delivery of specific anti-aggregant agents for platelets: kinetic analysis of the release mechanism.
The in vitro aqueous behaviour of a metacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)]benzoate (THEMA)/N,N'-dimethylacrylamide (DMA) copolymer with a THEMA molar content of 39% (labeled THDMA39) has been investigated. This composition has been selected to achieve a system able to keep both the non-water solubility during the release and the resorbability (and the water solubility) after the completion of the drug release. This copolymer exhibited, at pH 7.4, a constant release during several months, very interesting for a long term treatments required for the application of some cardiovascular devices. A kinetic model has been developed to explain the pseudo-zero-order kinetics of the release process. This model, which considers (from the aqueous studies) a linear increase with time of the amount of water present in the polymeric matrix, has been able to fit adequately the experimental data.
Instituto de Ciencia y Tecnología de Polímeros, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain. gallardo@ictp.csic.es
Alberto
A
Gallardo
Gema
G
Rodríguez
Mar
M
Fernández
María Rosa
MR
Aguilar
Julio
J
San Román
D000178:Acrylamides / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D001792:Blood Platelets / Q000187:drug effects*; D015195:Drug Design; D005609:Free Radicals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry*; D012459:Salicylates / Q000737:chemistry; D013917:Thrombin / Q000737:chemistry; D013997:Time Factors; D014050:Toluene / Q000031:analogs & derivatives* / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000178:Acrylamides; D001672:Biocompatible Materials; D005609:Free Radicals; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; D012459:Salicylates; D014867:Water; C016167:triflusal; D014050:Toluene; C055606:3-trifluoromethylbenzoate; D013917:Thrombin; C045985:methacrylamide