Capillary Electrophoresis Chiral Separation for Enantiomeric Purity Determination of a Basic Drug in Pharmaceutical Formulations

Capillary electrophoresis using a running buffer composed of β-cyclodextrin as the chiral selector and ethanolamine mesylate at pH 9.6 is being used to monitor the stereochemical stability of a hydrophobic drug, containing two chiral centers, in two different formulated self-emulsifying drug delivery system (SEDDS) products. The separation takes place in less than 25 min. Strategies for enhancing the method reproducibility and detection sensitivity in the lower potency formulation are presented. The results demonstrating the specificity, assay precision, recovery, linearity and range achieved during the method validation experiments are presented in this paper.Presented at: CE in the Biotechnology and Pharmaceutical Industries: 7th Symposium on the Practical Applications for the Analysis of Proteins, Nucleotides and Small Molecules, Montreal, Canada, August 12–16, 2005.     

Indirect Methods For Determination of The Protective Effects of Coating Films on The Surface of Crystals

The extents of the protective effects of coating films on the surface of crystals were determined. Three different samples were made with different quantities of coating fluid (Sepifilm LP 010 in 10% aqueous solution). Since the atomizing rate was constant, the coating time increased in parallel with the volume of coating fluid applied. The direct measurement of film thickness and smoothness is very difficult, and therefore indirect methods were used. Dimenhydrinate was chosen as model drug; this is a heat-sensitive antihistamine with a low melting point. This temperature can be reached during the tableting process. The behaviour of samples on exposure to heat was examined by differential scanning calorimetry. The water uptakes of the samples were determined with an Enslin apparatus. Plasticity was studied with an instrumented tablet machine. These indirect methods (thermal conductivity, water uptake and plasticity measurements) revealed connections between the results of the various experiments. An overlong coating time decreased the protective effect of the coating film. This revised version was published online in August 2006 with corrections to the Cover Date.     

Time Evolution of Vibration-Induced Excited State Decay

A simple model consisting of two electronic levels and one vibrational mode (phonon) was theoretically studied. The electronic-vibrational interaction was linear in the vibrational displacement. The vibrational mode was taken in the harmonic approximation and was attached to the thermal bath formed by the ambient environment. The kinetic constants of the vibrational dissipation were of the second order in the vibrational-bath coupling and were taken in the Markovian limit. Although, depending on the parameters of the model, different curves of the non-radiative vibration-induced excited state decay were obtained, in general, three time intervals, corresponding to different physical behaviour, were found. In the short-time interval, small oscillations superimposed on the excited state decay were observed. They were determined by the vibrational frequency and influenced by electronic-vibrational coupling. In the middle-time interval, almost quasi-exponential decay was detected; its rate constant increased with stronger electronic-vibrational interaction and speed of vibrational relaxation. In the long-time interval, the decay was very slow and, under special conditions, even an asymptotic non-zero excited state population was observed. Its value increased with the strength of the off-diagonal electron-vibrational coupling. Links of the parameters of the model with quantum chemical terms were estimated.     

Towards the Evaluation of the Relevant Degrees of Freedom in Nonlinear Partial Differential Equations

We investigate an operator renormalization group method to extract and describe the relevant degrees of freedom in the evolution of partial differential equations. The proposed renormalization group approach is formulated as an analytical method providing the fundamental concepts of a numerical algorithm applicable to various dynamical systems. We examine dynamical scaling characteristics in the short-time and the long-time evolution regime providing only a reduced number of degrees of freedom to the evolution process.     

Une nouvelle méthode de raffinement de maillage spatio-temporel pour l'équation des ondes

In the present Note we introduce an extension of the conservative space–time mesh refinement method presented by Fouquet et al. We also propose a post-treatment of the solution that reduces the spurious phenomena due to the non-conformity between the time meshes. A reinterpretation of the equations in terms of new unknowns leads to a new scheme with second order consistent coupling equations. Numerical experiments in 2D and a plane wave analysis for the 1D model show that the method is second order accurate for an arbitrary refinement. To cite this article: J. Rodríguez, C. R. Acad. Sci. Paris, Ser. I 339 (2004).     

Extraction-ability and -selectivity of tetra-aza-crown ethers for transition metal cations

In order to investigate the relative effects of the differences between the structures and lipophilicities of 1, 10-dioxa-4, 7, 13, 16-tetra-azacyclo-octadecane (TA-18-crown-6) and the tetrabenzyl derivative of 1,10-dioxa-4, 7, 13, 16-tetra-azacyclo-octadecane (TBTA-18-crown-6) on their extraction-abilities and -selectivities for transition metal cations, constants of the overall extraction (logK _ex) of 1:1 (M:L) complexes, the distribution (K _D) for two diluents (CH₂Cl₂ and CHCl₃) with different dielectric constants have been determined at 25 ± 0.1 °C. The magnitude of logK _ex is largely determined by that of K _D. The equilibrium constants of TA-18-crown-6 have been compared with those of TBTA-18-crown-6. It is found that:(i) logK _ex sequences of TA-18-crown-6 and TBTA-18-crown-6 for transition metals in CH₂Cl₂ lie in order: Fe³⁺ > Cu²⁺ > Mn²⁺ > Co²⁺ > Cd²⁺ > Ni²⁺ > Zn²⁺ and Fe³⁺ > Cu²⁺ > Co²⁺ > Mn²⁺ > Ni²⁺ > Cd²⁺ > Zn²⁺ respectively; (ii) the stability sequences of two types of tetra-aza-crown ethers with the transition metal cations in CHCl₃ are the same as follows: Fe³⁺ > Ni²⁺ > Cu²⁺ > Co²⁺ > Zn²⁺ > Cd²⁺ > Mn²⁺, and (iii) unusual selectivities are observed for transition metal-tetra-aza-crowns, e.g. the high Fe³⁺/M ⁿ⁺ selectivity factors (S_f) of TA-18-crown-6, except for the competitive-extractions for the special case in CHCl₃ of TBTA-18-crown-6, it was found that the Mn²⁺/M ⁿ⁺ values were relatively higher according to the other transition metal cations. A systematic sequence in these two types of solvents is not found for a given transition metal cation in terms of the variation of selectivity with the tetra-aza-crown ethers. The results provide alternatives for the rational design of other specific ligands on the transition metal cations.