Gabriel Llabres

Development of a non-surfactant parenteral formulation of miconazole by the use of cyclodextrins

Abstract Miconazole is an antimycotic drug exhibiting a very poor water solubility ( μ g/ml). It has been shown that cyclodextrins (CDs) are able to form inclusion complexes with miconazole and that they are able to increase its aqueous solubility. Miconazole is a weak base whose solubility depends of the pH. The purpose of this study was to investigate the influence of both CDs and different acids on the solubility of miconazole. It was found that a synergistic effect existed between CDs and different acids. The combination of hydroxypropyl- β CD (HP- β CD) (100 mM) or sulfobutylether 7- β CD (SBE 7 - β CD) (50 mM) and lactic acid (50 mM) allowed to dissolve more than 10 mg of miconazole per ml. NMR studies confirmed the formation of an inclusion complex miconazole–CD in an acidic medium. It was also shown by the NMR studies that the complex formed was a 1:1 complex. These results demonstrate that it is possible to develop a parenteral aqueous solution of miconazole without surfactant.

Structural characterisation of glassy phases in the system Na2O–Al2O3–P2O5 by MAS and solution NMR, EXAFS and vibrational spectroscopy

The structure of sodium aluminophosphate glasses with a fixed O/P ratio of 4 and 3.5 has been investigated. For the monophosphate compositions, the phosphate network is completely depolymerised so that the glassy network is built through the aluminium atoms which are distributed on three different sites but lying mainly in tetrahedral coordination. 31P Magic angle spinning (MAS)-NMR spectra show the existence of three different cationic environments for the PO43− ions. In the glasses with the diphosphate compositions, we observed the disproportionation of some diphosphate groups into monophosphate and triphosphate ions crosslinked by the aluminium atoms whose average coordination increases. The diphosphate groups give a typical vibrational spectrum but the detection of the other phosphate molecular groups is not obvious. The Ga–Al substitution allows better vibrational assignment. MAS-NMR spectra of these two cations show that these two conditional glass former does not behave exactly in the same way in the glassy state.

Interaction between class B β-lactamases and suicide substrates of active-site serine β-lactamases

The most widely used inactivators of active‐site serine β‐lactamases behave as substrates of four class B metallo‐β‐lactamases, but the efficiency of the catalytic process can vary by several orders of magnitude. A comparison of the kinetic parameters for the α and β isomers of 6‐iodopenicillanic acid shows that there is no general preference for the α isomer and that the efficient hydrolysis of imipenem by these enzymes must rest on other factors.

Structure cristalline et moléculaire du bromure d'o-formyl phénylsélényle (C7H5OSeBr)

The crystal and molecular structure of o-formylphenyltellurenyl bromide has been determined by three-dimensional X-ray analysis. Crystals are monoclinic (P21/c) and the unit cell has the dimensions a = 12.533, b = 5.839, c = 11.706 A and β = 102.48°. The refinement of the structure by Fourier and block-diagonal matrix least-squares methods has led to a final R value of 0 081. The molecule has a planar cis configuration. The coordination of the Te(II) atom is described with the model proposed by Foss. The existence of a Te-O bond is discussed.

Structural characterization of glassy phases in the system Na2O-Ga2O3-P2O5 by MAS and solution NMR and vibrational spectroscopy: II. Structure of the phosphate network.

The structure of the phosphate network of glasses in the system Na2O-Ga2O3-P2O5 has been investigated as a function of the Na/Ga molar ratio and the phosphate composition corresponding to a mono, di, tri, tetra and meta phosphate stoichiometry. The glass is made of phosphate molecular groups of different lengths linked by the cations with rather ionic (Na) or more covalent (Ga) bonds except in the case of the orthophosphate composition for which we only found isolated PO4(3-) ions. The vibrational spectra are sensitive to composition variations but the band width and the couplings between the different groups prevent any quantitative determination. 31P MAS-NMR gives an in-situ information on the P environment in the glass but the signals are often large and ill defined so that the assignment is not at all straightforward. On the other hand, 31P solution NMR gives sharper signals, allowing more quantitative determinations but the dissolution process always introduces some indeterminacy on the real glass structure which can be minimized by a careful preparation of the solution.

Guianensine, a zwitterionic alkaloid from strychnos guianensis

The isolation and structural determination of an alkaloid isolated from the stem bark of Strychnos guianensis is described. Elucidation of its structure is based mainly on 1D and 2D NMR studies. The new alkaloid has a zwitterionic asymmetrical bis-indole structure and is named guianensine.

N.M.R. and conformational analysis of some Te-containing ortho-substituted benzaldehydes

We report the analysis of the high-resolution proton magnetic resonance spectra of some 2-halotellurenyl-benzaldehydes (Cl, Br, I) and of 2-methyltellurobenzaldehyde, considered as ABCD spin systems. The identification of the long-range couplings in these molecules shows that they all have a ‘cis’ conformation of the aldehyde carbonyl relative to the ortho-substituent. An electronic model which explains this conformation in the case of the haloderivatives is suggested. It agrees with infra-red measurements. In the case of the methylated compound, another model is proposed to account for our observations, in agreement with the results reported by Andrieu and Ruwet for 2-methoxy, 2-methylthio- and 2-methylselenobenzaldehyde. We observed coupling of the methyl protons with the nuclei 123Te (27·0 Hz) and 125Te (32·5 Hz) in 2-methyltellurobenzaldehyde.

Structural characterization of glassy phases in the system Na2O–Ga2O3–P2O5 by MAS-NMR, EXAFS and vibrational spectroscopy. I. Cations coordination

The cationic coordinations of phosphate based gallium sodium glasses in the system Na2O-Ga2O3-P2O5 have been studied by several techniques (71Ga and 23Na MAS-NMR, EXAFS and vibrational spectroscopies) in order to study the relationship between the structure and the chemical composition. We found that three different environments are available for the gallium ions while it is very difficult to get accurate information on the sodium coordinations. Our data show that in orthophosphate glasses, gallium is mainly tetrahedral but when the mean phosphate chain length increases, its coordination becomes more and more octahedral. In these glassy structure, it becomes then possible to dissolve large amounts of typically octahedral cations like Fe3+ or Cr3+.

Etude par RMN de composés organiques contenant des chalcogènes—VIII. RMN du 13C dans la chromannone, la chromone, la coumarannone-3 et la coumarine et leurs analogues soufrés, séléniś et tellurés

Abstract 13 C NMR spectra of the title compounds have been fully assigned. The results have been compared with those relative to other chalcogenated compounds, such as anisole, phenyl benzoate, benzofuran,… and their analogs. In chalcogenochromones and -coumarines, the heteroatom lone pair delocalization spreads to some extent over the heterocyclic part of the molecules, while in chalcogenochromanones and -indoxyles, it only extends to the homocycle. This electronic effect seems also to affect the heavy atom effect exhibited by Te-containing compounds.

Protein patterns, osmolytes, and aldose reductase of L-929 cells exposed to hyperosmotic media

L‐929 cells acclimated to media made hyperosmotic (600 mosmol/kgH2O) by addition of NaCl, sorbitol, or mannitol show, on SDS‐polyacrylamide gels, a markedly enhanced protein band at 40 kDa, most likely corresponding to the enzyme aldose reductase. The effect was not observed in cells acclimated to a medium rendered hyperosmotic by addition of proline. The major organic osmolyte accumulated is sorbitol in cells acclimated to high‐sorbitol or high‐NaCl medium, proline in cells acclimated to high‐proline medium. Cells acclimated to any of these hyperosmotic media display unaltered Na+ levels and similarly increased K+ levels and decreased Cl− levels. These results are interpreted in terms of the mechanisms involved in aldose reductase induction and in regulation of the enzyme activity in long‐term acclimation to hyperosmotic media.