Optimization of glibenclamide tablet composition through the combined use of differential scanning calorimetry and D-optimal mixture experimental design.

A systematic analysis of the influence of different proportions of excipients on the stability of a solid dosage form was carried out. In particular, a d-optimal mixture experimental design was applied for the evaluation of glibenclamide compatibility in tablet formulations, consisting of four classic excipients (natrosol as binding agent, stearic acid as lubricant, sorbitol as diluent and cross-linked polyvinylpyrrolidone as disintegrant). The goal was to find the mixture component proportions which correspond to the optimal drug melting parameters, i.e. its maximum stability, using differential scanning calorimetry (DSC) to quickly obtain information about possible interactions among the formulation components. The absolute value of the difference between the melting peak temperature of pure drug endotherm and that in each analysed mixture and the absolute value of the difference between the enthalpy of the pure glibenclamide melting peak and that of its melting peak in the different analyzed mixtures, were chosen as indexes of the drug-excipient interaction degree.

Micellar electrokinetic chromatography for the simultaneous determination of ketorolac tromethamine and its impurities. Multivariate optimization and validation.

A simple, fast and selective micellar electrokinetic chromatographic (MEKC) method for the simultaneous assay of ketorolac tromethamine and its known related impurities (1-hydroxy analog of ketorolac, 1-keto analog of ketorolac and decarboxylated ketorolac), in both drug substance and coated tablets, is described. The compounds were detected at 323 nm, and flufenamic acid (FL) and tolmetin (TL) were chosen as internal standards to quantify ketorolac tromethamine and impurities, respectively. The multivariate optimization of the experimental conditions was carried out by means of the response surface study, considering as responses the resolution values and analysis time. The optimized background electrolyte (BGE) consisted of a mixture of 13 mM boric acid and phosphoric acid, adjusted to pH 9.1 with 1 M sodium hydroxide, containing 73 mM sodium dodecyl sulfate (SDS). Optimal temperature and voltage were 30 degrees C and 27 kV. Applying these conditions, all compounds were resolved in about 6 min. The related substances could be quantified up to the 0.1% (w/w) level. Validation was performed, either for drug substances and drug product, evaluating selectivity, robustness, linearity and range, precision, accuracy, detection and quantitation limits and system suitability.

A polarographic, oxygen-selective, vibrating-microelectrode system for the spatial and temporal characterisation of transmembrane oxygen fluxes in plants.

A simple procedure is described for the fabrication of micrometer to nanometer-scale platinum electrodes to be used in a vibrating oxygen-selective system. The electrode was prepared by etching a fine platinum wire and insulating it with an electrophoretic paint. The dimensions allowed this electrode to be used with the "vibrating probe technique" in exploratory studies aimed at mapping and measuring the patterns of net influxes as well as effluxes of oxygen in Olea europaea L. leaves and roots with spatial and temporal resolutions of a few microns and a few seconds, respectively. The magnitude and spatial localisation of O2 influxes in roots was characterised by two distinct peaks. The first, in the division zone, averaged 38 +/- 5 nmol m(-2) s(-1); the second, in the elongation region, averaged 68 +/- 6 nmol m(-2) s(-1). Long-term records of oxygen influx in the elongation region of the root showed an oscillatory regime characterised by a fast oscillation with periods of about 8-9 min. In leaves, the system allowed the measurement of real-time changes in O2 evolution following changes in light. Furthermore, it was possible to obtain "topographical" images of the photosynthetically generated oxygen diffusing through different stomata from a region of the leaf of 120 microm x 120 microm. The combination of topographic and electrochemical information at the micrometer scale makes the system an efficient tool for studying biological phenomena involving oxygen diffusion.