Mira Čakar

Acid–base equilibria and solubility of loratadine and desloratadine in water and micellar media

Acid-base equilibria in homogeneous and heterogeneous systems of two antihistaminics, loratadine and desloratadine were studied spectrophotometrically in Britton-Robinsons buffer at 25 degrees C. Acidity constant of loratadine was found to be pK(a) 5.25 and those of desloratadine pK(a1) 4.41 and pK(a2) 9.97. The values of intrinsic solubilities of loratadine and desloratadine were 8.65x10(-6) M and 3.82x10(-4) M, respectively. Based on the pK(a) values and intrinsic solubilities, solubility curves of these two drugs as a function of pH were calculated. The effects of anionic, cationic and non-ionic surfactants applied in the concentration exceeding critical micelle concentration (cmc) on acid-base properties of loratadine and desloratadine, as well as on intrinsic solubility of loratadine were also examined. The results revealed a shift of pK(a) values in micellar media comparing to the values obtained in water. These shifts (DeltapK(a)) ranged from -2.24 to +1.24.

Determination of bifonazole in creams containing methyl- and propyl p-hydroxybenzoate by derivative spectrophotometric method

A second order derivative spectrophotometric method for the determination of bifonazole in the presence of methyl- and propyl p-hydroxybenzoate as preservatives has been developed. The determination was performed in a 0.1 M HCl solution at 241.5 nm, a wavelength corresponding to the intersection of the second order derivative spectra (2D) of methyl- and propyl p-hydroxybenzoate with the axis (zero-crossing point). On the basis of the knowledge of acidity constants and solubility, as well as of the investigations of zero-order and 2D spectra of bifonazole and preservatives, these conditions were chosen as optimal ones. A calibration curve constructed for bifonazole concentrations ranging from 1.5 to 15 microg/ml had a correlation coefficient of 0.9998. Reliability and reproducibility of the method was checked by analyzing laboratory mixtures of bifonazole and preservatives (recovery 99.97-102.7%; RDS 0.48-1.46%). The proposed method was applied for the determination of bifonazole in a commercial cream formulation. The mean value of bifonazole obtained per 100 g cream was 1.029 g (102.9% of the labeled claim) with a RSD of 0.60%.

Influence of sodium dodecyl sulfate on the kinetics of complex formation between [PdCl(dien)]+ and sulfur containing ligands l-cysteine and glutathione

Abstract The effect of sodium dodecyl sulfate (SDS) micelles on the kinetics of the complex formation between [PdCl(dien)]+ and sulfur containing ligands l -cysteine and glutathione (GSH) was investigated by using the stopped-flow technique under pseudo-first order conditions (ligand in excess) in the acidity range from pH 1 to 6. The presence of anionic micelles induced the acceleration of the complex formation in the entire acidity range with the maxima corresponding to the first protolytic constant of the ligands. This effect was interpreted in terms of the attractive electrostatic interaction between reacting species and the micellar surface and their effective concentration in the vicinity of micelles. An increase of the ionic strength leads to a decrease of the rate of complex formation in the presence of anionic micelles due to competition of reactive species with cations originating from inert salt for the micellar surface. The calculation of activation parameters revealed that the entropy of activation is strongly negative in the presence and in the absence of micelles, which is compatible with an associative reaction mechanism.

Spectrophotometric and electrochemical study of protolytic equilibria of some oximes-acetylcholinesterase reactivators.

Newly synthesized oximes, mono and bis imidazole derivatives, which promise to be more effective acetylcholinesterase reactivators than standard antidotes used, were investigated by spectrophotometric and electrochemical methods. The electrochemical investigations confirmed the existence of overlapping equilibria, obtained by spectrophotometric methods. Dissociation constants of those oximes were also obtained by numerical treatment of overlapping equilibria, using the Lavendberg Marquardt least square method, and when compared with the same for some similar compounds, were found to be very effective acetylcholinesterase reactivators. The distribution of ionic forms of the investigated oximes, as a dependence of pH values, was calculated from the obtained values of dissociation constants. The results indicated that many oxime anions will be available at physiological pH 7.4 and a relative increased ability to reactivate inhibited acetylcholinesterase could be expected.

Comparison of HPTLC and HPLC for determination of econazole nitrate in topical dosage forms

HPTLC and HPLC methods have been established for separation and quantitative determination of econazole nitrate. HPTLC was performed on silica gel plates with n-butyl acetate–carbon tetrachloride–methanol–diethylamine, 3 + 6 + 2.5 + 0.5 (v/v), as mobile phase. Chromatographic zones, or spots, of econazole base and nitrate were used to quantify econazole nitrate. HPLC was performed on amino and C8 columns with acetonitrile–water, 30 + 70 (v/v), pH 2.5 (adjusted with phosphoric acid), as a mobile phase. The chromatograms were characterized by single peaks of econazole (amino column) or nitrate (C8 column). The methods were successfully used for determination of econazole nitrate in spray solution and vaginal pessaries.

Simultaneous HPTLC determination of imidazole antimycotics and parabens in creams

A simple and reliable HPTLC method has been developed for simultaneous determination of antimycotics (bifonazole and econa-zole nitrate) and preservatives (methyl- and propylparaben) in medicinal creams. Chromatography was performed on silica gel plates with ethyl acetate-n-hexane-methanol-ammonia-diethylamine, 0.5 + 4 + 0.8 + 0.4 + 2 (v/v) as mobile phase. Chroma-tographic zones corresponding to spots of econazole nitrate, bifona-zole, and parabens were scanned in reflectance/absorbance mode at λ= 230, 250, and 300 nm, respectively. The method was successfully applied to simultaneous determination of the compounds in commercially available pharmaceuticals.

Kinetic determination of trace levels of selenium(IV) and total selenium by nile blue A/hydrogen peroxide method

A kinetic method for the determination of selenium(IV) traces is proposed, based on its inhibitory action on the oxidation of Nile Blue A by hydrogen peroxide in phosphate buffer (pH 10.5). A linear dependence was established between the rate of the proposed indicator reaction and selenium concentration in the range 9.5 × 10−2-1.58 ng cm−3. The experimental conditions of maximal selenium effect were established. Selenium, determined by the tangent method, was determined at concentrations over the range 0.22–1.26 ng cm−3, with relative standard deviations up to 4.5%. The reaction rate was followed spectrophotometrically. The effect of foreign ions on the accuracy of this method was also investigated. The method was applied to the determination of selenium in pharmaceutical preparations and wheat flour.

Kinetic determination of 1-{[4′-(aminocarbonyl)-1′-pyridinio]-methoxymethyl}-2-(hydroxyiminomethyl)pyridinium dichloride (HI-6) alone and in binary mixtures with 1,1′-(oxydimethylene)bis(4-hydroxyiminomethylpyridinium) dichloride (toxogonin) and 1,1′-(propane-1,3-diyl)bis(4-hydroxyiminomethylpyridinium) dibromide (TMB-4)

The oxime, 1-{[4′-(aminocarbonyl)-1′-pyridinio]methoxymethyl}-2-(hydroxyiminomethyl)pyridinium dichloride (HI-6), catalyses the reaction of gold(III) with potassium iodide in alkaline media. As HI-6 is used as an extremely effective agent against nerve gas poisoning, this effect has been utilised to develop a kinetic method for the determination of HI-6. By using a stopped-flow technique it was possible to determine HI-6 in concentrations from 3.3 × 10–7 to 6.0 × 10–6M, with a relative standard deviation of 3%. The method was checked by determining HI-6 in various different tablets. The proposed method can be applied to the analysis of mixtures of HI-6 with the bispyridinium oximes, 1,1′-(oxydimethylene)bis(4-hydroxyiminomethyl-pyridinium) dichloride (Toxogonin) and 1,1′-(propane-1,3-diyl)bis(4-hydroxyiminomethylpyridinium) dibromide (TMB-4).