Determination of Fexofenadine in Tablets by Capillary Electrophoresis in Free Solution and in Solution with Cyclodextrins as Analyte Carriers

ABSTRACT

Capillary electrophoresis (CE) methods for the determination of fexofenadine (FEX) in commercial pharmaceuticals were developed. It was demonstrated that FEX could be effectively analyzed in free solution cationic CE at low pH. Another analytical approach studied was based on cyclodextrin (CD) modified CE where highly charged CD derivatives served as analyte carriers. In this way, the separation range was spread to physiological pH region and a CE analysis of FEX, present actually in its zwitterionic form, could be accomplished. Several parameters affecting the separations were studied, including the type and concentration of carrier ion, counterion, analyte carrier, and pH of the buffer. The methods based on the free solution CE and CD-modified CE were compared each other, validated, and applied for the determination of FEX in tablets.     

Dielectric properties of polyarylate (PAr) around the glass transition

Dielectric characterization of the α-relaxation in polyarylate (PAr) has been carried out by means of a dielectric spectroscopy technique in a frequency range of 10–30 kHz. Complementary thermally stimulated depolarization currents (TSDC) and differential scanning calorimetry d.s.c.) measurements have also been performed. The results are interpreted in terms of the standard Cole-Cole plot and Havriliak-Negami distribution for the dielectric relaxation times. Information about the temperature and frequency dependence of a.c. conductivity is also obtained from the experimental curves. However, the behaviour of the main dielectric relaxation time is deduced from the experimental data in a wide range of temperature around the glass transition. This behaviour results in close agreement with the theoretical predictions of a free-volume approach for the dielectric α-relaxation recently proposed by the authors.     

Nanocomposites derived from cellulose acetate and highly branched alkoxysilane

Highly branched alkoxysilane (HB) units were prepared in situ via a Michael‐type reaction between pentaerythrithol triacrylate and aminopropyltriethoxysilane. These units were used as an inorganic component for the modification of cellulose acetate (CA) films using the sol–gel process. The thermal and dynamic‐mechanical behaviors, the morphology, and the dimensional stability of the modified CA films were analyzed. The siloxane‐modified CA films showed thermal stability similar to pure CA, but the residue content at 900°C increased with the addition of HB units. The morphology of these films was characterized by siloxane nanodomains dispersed in the CA matrix, with good interfacial adhesion between the phases. Moreover, the CA/siloxane nanocomposite films showed improved dimensional stability in comparison with CA, i.e., in the presence of HB, the dimensional change was reduced to around 50% of the value observed for pure CA. Finally, a complex dynamic‐mechanical behavior was obtained for the nanocomposite films, as a consequence of the heterogeneous morphology. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Development of Microsatellite Markers in the Branched Broomrape Phelipanche ramosa L. (Pomel) and Evidence for Host-Associated Genetic Divergence

Phelipanche ramosa is a parasitic plant that infects numerous crops worldwide. In Western Europe it recently expanded to a new host crop, oilseed rape, in which it can cause severe yield losses. We developed 13 microsatellite markers for P. ramosa using next-generation 454 sequencing data. The polymorphism at each locus was assessed in a sample of 96 individuals collected in France within 6 fields cultivated with tobacco, hemp or oilseed rape. Two loci were monomorphic. At the other 11 loci, the number of alleles and the expected heterozygosity ranged from 3 to 6 and from 0.31 to 0.60, respectively. Genetic diversity within each cultivated field was very low. The host crop from which individuals were collected was the key factor structuring genetic variation. Individuals collected on oilseed rape were strongly differentiated from individuals collected on hemp or tobacco, which suggests that P. ramosa infecting oilseed rape forms a genetically diverged race. The microsatellites we developed will be useful for population genetics studies and for elucidating host-associated genetic divergence in P. ramosa.     

Probing Ambiguous Base‐Pairs by Genetic Transformation with XNA Templates

The templating potential of anhydrohexitol oligonucleotides bearing ambiguous bases was studied in vivo, by using a selection screen for mosaic heteroduplex plasmids in Escherichia coli. 1,5‐Anhydro‐2,3‐dideoxy‐2‐(5‐nitroindazol‐1‐yl)‐D ‐arabino‐hexitol showed the greatest ambiguity among the three nucleosides tested. At most two successive ambiguous bases could be tolerated on hexitol templates read in bacterial cells. Hexitol nucleosides bearing simplified heterocycles thus stand as promising monomers for generating random DNA sequences in vivo from defined synthetic oligonucleotides.     

Effect of Oxime Ether Incorporation in Acyl Indole Derivatives on PPAR Subtype Selectivity

Compounds that simultaneously activate peroxisome proliferator‐activated receptor (PPAR) subtypes α and γ have the potential to effectively treat dyslipidemia and type 2 diabetes (T2D) in a single pharmaceutically active molecule. The frequently observed side effects of selective PPARγ agonists, such as edema and weight gain, were expected to be overcome by using additive PPARα activity, leading to dual PPARα/γ agonists with balanced activity for both subtypes. Herein we report the discovery, synthesis, and optimization of a new series of α‐ethoxyphenylpropionic acid bearing 5‐ or 6‐substituted indoles. The incorporation of oxime ethers on the carbonyl portion of the benzoyl group can bring the PPARα/γ potency ratio equal to or slightly greater than one, as is the case for compounds 20 c and 21 a . Compound 20 c shows high efficacy in an ob/ob mouse model of T2D and dyslipidemia, similar to that of rosiglitazone and tesaglitazar, but with a significant increase in body weight gain. In contrast, compound 21 a , less potent as a dual PPARα/γ activator than 20 c , showed an interesting pharmacological profile, as it elicits a decrease in body weight relative to reference compounds.     

Ceramics based on partly stabilized zirconium dioxide: technology,structure, properties,and behavior under dynamic action

Technology is described for manufacturing dense ceramic from very fine powder based on zirconium dioxide partly stabilized with yttrium oxide. Some engineering properties of the manufactured ceramic are defined. Its microstructure and phase composition are studied. Ceramic properties with impact-wave loading are studied, and values of dynamic elastic limit and spalling strength are obtained.     

Polyunsaturated Fatty Acid Concentrates of Carp Oil: Chemical Hydrolysis and Urea Complexation

The aims of this study were to compare three treatments in the chemical hydrolysis reaction of bleached oil from carp (Cyprinus carpio) heads and to obtain polyunsaturated fatty acid concentrates by urea complexation. The three treatments were carried out with different oil:ethanol molar ratios. In the treatment with a 1:39 molar ratio, a higher yield of free fatty acids was found. These fatty acids were submitted to urea complexation (−10 °C for 20 h, and urea–fatty acid ratio of 4.5–1). There was a 31.4% increase in monounsaturated and polyunsaturated fatty acids (MUFA and PUFA) content and a 75% decrease in saturated fatty acids (SAF) content. An increase of 85.4% in the EPA + DHA content was found. The non-urea complexing fraction can be considered a rich source of MUFA and PUFA with a total amount of 88.9%.     

Synthesis and characterizations of poly(ethylene-co-vinylalcohol)-grafted-poly(3-hydroxybutyrate-co-hydroxyvalerate) copolymers

Poly(ethylene-co-vinylalcohol)-grafted-poly(3-hydroxybutyrate-co-hydroxyvalerate) (EVOH-g-PHBV) was prepared by a catalyzed grafting of PHBV onto immiscible EVOH. These reactions were performed at high temperature in the molten state. The choices of Tin(II) bis(2-ethylhexanoate) (Sn(Oct)₂) and 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD), as catalyst, were justified by a first study in an internal mixer. The catalyst quantity, reaction temperature and reaction time were optimized to apply them in the conditions of a reactive extrusion process with a co-rotating twin screw extruder. High reaction temperature, from 180 °C to 220 °C, associated to intensive mixing led to efficient grafting of PHBV onto EVOH, compatible with short residence times required.Rheological, thermal and morphological analyses were conducted to characterize the obtained copolymers. Molecular weights were determined by SEC. SEM imaging were made on cryo-fractured surfaces of blends extruded with and without catalyst. In most of reaction conditions, a compatible blend was obtained with a fine micro phase separation. Grafted copolymers were only obtained when well defined and controlled conditions are applied.     

Tight binding of the antitumor drug ditercalinium to quadruplex DNA

The structural selectivity of the DNA-binding antitumor drug ditercalinium was investigated by competition dialysis with a series of nineteen different DNA substrates. The 7H-pyridocarbazole dimer was found to bind to double-stranded DNA with a preference for GC-rich species but can in addition form stable complexes with triplex and quadruplex structures. The preferential interaction of the drug with four-stranded DNA structures was independently confirmed by electrospray mass spectrometry and a detailed analysis of the binding reaction was performed by surface plasmon resonance (SPR) spectroscopy. The BIAcore SPR study showed that the kinetic parameters for the interaction of ditercalinium with the human telomeric quadruplex sequence are comparable to those measured with a duplex sequence. Slow association and dissociation were observed with both the quadruplex and duplex structures. The newly discovered preferential binding of ditercalinium to the antiparallel quadruplex sequence d(AG(3)[T(2)AG(3)](3)) provides new perspectives for the design of drugs that can bind to human telomeres.