title: Statistical optimisation of diclofenac sustained release pellets coated with polymethacrylic films.
abstract: The objective of the present study was to evaluate three formulation parameters for the application of polymethacrylic films from aqueous dispersions in order to obtain multiparticulate sustained release of diclofenac sodium. Film coating of pellet cores was performed in a laboratory fluid bed apparatus. The chosen independent variables, i.e. the concentration of plasticizer (triethyl citrate), methacrylate polymers ratio (Eudragit RS:Eudragit RL) and the quantity of coating dispersion were optimised with a three-factor, three-level Box-Behnken design. The chosen dependent variables were cumulative percentage values of diclofenac dissolved in 3, 4 and 6 h. Based on the experimental design, different diclofenac release profiles were obtained. Response surface plots were used to relate the dependent and the independent variables. The optimisation procedure generated an optimum of 40% release in 3 h. The levels of plasticizer concentration, quantity of coating dispersion and polymer to polymer ratio (Eudragit RS:Eudragit RL) were 25% w/w, 400 g and 3/1, respectively. The optimised formulation prepared according to computer-determined levels provided a release profile, which was close to the predicted values. We also studied thermal and surface characteristics of the polymethacrylic films to understand the influence of plasticizer concentration on the drug release from the pellets.
authors.affiliation: R&D Division, KRKA, d.d., Smarjeska cesta 6, 8501, Novo mesto, Slovenia.
authors.forename: A
authors.initials: A
authors.lastname: Kramar
authors.forename: S
authors.initials: S
authors.lastname: Turk
authors.forename: F
authors.initials: F
authors.lastname: Vrecer
mesh_terms: D004008:Diclofenac / Q000737:chemistry*; D004339:Drug Compounding; D008956:Models, Chemical; D010968:Plasticizers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011237:Predictive Value of Tests; D012995:Solubility; D013608:Tablets, Enteric-Coated
chemical_list: D010968:Plasticizers; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; D004008:Diclofenac; C030613:polymethacrylic acid