title: Application of experimental design methodology in development and optimization of drug release method.
abstract: The aim of our research was to apply experimental design methodology in the development and optimization of drug release methods. Diclofenac sodium (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid monosodium salt) was selected as a model drug and Naklofen retard prolonged release tablets, containing 100 mg of diclofenac sodium, were chosen as a model prolonged release system. On the basis of previous results, a three-level three-factorial Box-Behnken experimental design was used to characterize and optimize three physicochemical parameters, i.e. rotation speeds of the stirring elements, pH, and ionic strengths of the dissolution medium, affecting the release of diclofenac sodium from the tablets. The chosen dependent variables (responses) were a cumulative percentage of dissolved diclofenac sodium in 2, 6, 12 and 24 h. For estimation of coefficients in the approximating polynomial function, the least square regression method was applied. Afterwards, the information about the model reliability was verified by using the analysis of variance (ANOVA). The estimation of model factors' significance was performed by Student's t-test. For investigation of the shape of the predicted response surfaces and for model optimization, the canonical analysis was applied. Our study proved that experimental design methodology could efficiently be applied for characterization and optimization of analytical parameters affecting drug release and that it is an economical way of obtaining the maximum amount of information in a short period of time and with the fewest number of experiments.
authors.affiliation: Krka, d.d., Novo mesto, R&D, Smarjeska cesta 6, 8501 Novo mesto, Slovenia. maja.kincl@krka.biz
authors.forename: M
authors.initials: M
authors.lastname: Kincl
authors.forename: S
authors.initials: S
authors.lastname: Turk
authors.forename: F
authors.initials: F
authors.lastname: Vrecer
mesh_terms: D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001699:Biometry / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics*; D004008:Diclofenac / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D012107:Research Design / Q000592:standards; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D013607:Tablets; D004008:Diclofenac