Browsing by Subject "Cyclodextrins"
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Item Alkylmaltoside mediated nasal delivery of low molecular weight Heparin: In vitro and in vivo evaluations(Texas Tech University, 2004-05) Mustafa, FatimaThis study is designed to test the hypothesis that alkylmaltosides could be used as efficacious absorption enhancers for nasal delivery of enoxaparin, a low molecular weight heparin. The efficacy of the absorption enhancers was studied by monitoring the changes in plasma anti-factor Xa level after nasal administration of enoxaparin into anesthetized rats. In vivo reversibility study was performed to determine if the effect of the absorption enhancers on nasal membrane is reversible after acute administration of the formulations. Enoxaparin was formulated with alkylmaltosides containing varying alkyl chain lengths (octyl-, decyl-, dodecyl,- and tetradecyl-maltoside) in order to assess the role of hydrophobic chain length on the potency of the absorption enhancers. The mechanisms by which alkylmaltosides enhance permeation of enoxaparin across epithelial cells were investigated by studying the transport of radiolabelled enoxaparin and mannitol across human bronchial epithelial cells. In vitro cytotoxicity and transepithelial electric resistance recovery studies were performed to further assess the toxicity of the agents on epithelial cells. The results demonstrate that alkylmaltosides enhance enoxaparin absorption in a chain length and dose dependent manner. Of the alkylmaltosides tested, tetradecylmaltoside was most efficacious in enhancing nasal absorption of enoxaparin. It was found that the effect of octylmaltoside on nasal membrane diminishes with time and nasal mucosa re-establishes normal physiological barrier to drug absorption. Permeabilities of enoxaparin and mannitol increase in the presence of alkylmaltosides, suggesting that alkylmaftosides enhance nasal absorption of LMWH via paracellular route. Cytotoxicity studies revealed that octylmaltoside is the least toxic to the bronchial epithelial cells. Overall, the results suggest that nasal enoxaparin formulated v/ith alkylmaltosides could be a feasible alternative to subcutaneous enoxaparin.Item Cyclodextrin stationary phases: synthesis, characterization and applications in liquid chromatography(Texas Tech University, 1986-08) Alak, Ala MSince the creation of the first octadecyl bonded phase for High Performance Liquid Chromatography (HPLC), liquid chromatograhers have investigated a wide variety of bonded phases in their ongoing search for increased selectivity. These studies have led to a number of useful phases which appear to separate by different mechanisms such as hydrophobicity, ionic properties, electron density, and so forth. A highly selective chiral bonded phase material for HPLC and Thin Layer Chromatography (TLC), was produced by bonding cyclodextrin to silica gel particles through a spacer "arm" via a reproducible process which yields a stable, non-hydrolytic, non-nitrogen containing bonds. The synthesis, characterization and applications of these new stationary phases are described. The basic property of cyclodextrin molecules, which allows them to effect numerous chemical separations, is their ability to form selective inclusion complexes with a wide variety of organic and inorganic molecules. The formation of these inclusion complexes may occur by a combination of factors, such as hydrophobic effects, dipole-dipole interaction, hydrogen bonding (between the cyclodextrins hydroxyl groups and guest molecules) or the release of high energy water or modifier during complex formation. In general, binding to the cyclodextrin is governed by the molecule's ability to closely fit inside the cavity of the cyclodextrin, although the polarity of the molecule also plays an important role. Besides their ability to separate different kinds of enantiomers by HPLC and TLC, cyclodextrin stationary phases also proved to be the media of choice in separation of dlastereomers, geometrical and structural isomers, and many nonisomeric compounds. The effects of temperature, mobile phase composition, and flow rate upon chromatographic selectivity and resolution are described. The results indicate that cyclodextrin stationary phases are versatile, flexible and effective compared to conventional normal or reversed phase stationary phases.Item Cyclodextrins and micelles in separations(Texas Tech University, 1987-05) Ward, Timothy JosephNot availableItem Novel uses of organized media in chemical analysis(Texas Tech University, 1987-08) Spino, Larry AngeloMicelles and cyclodextrins have been utilized for years in a variety of chemical analysis techniques. This work considers some modern applications of micelles and cyclodextrins in chemical analysis. Micellar and cyclodextrin mobile phases (pseudophases) were used in liquid chromatography (LC). Cyclodextrin mobile phases were used in microcolumn LC for separating optical isomers of racemic nicotine and eight other racemic analogues of nicotine. This was the first reported facile and direct separation of these racemates. Synchronous luminescence was used as the detection method for liquid chromatography to identify polynuclear aromatic components that co-elute in the course of a LC separation. As many as five compounds could be identified from a single chromatographic peak. Several scans can be made easily for every eluting peak, however, a single scan is sufficient to produce a complete synchronous luminescence spectra of a complex mixture. The micellar matrix served as the mobile phase and produced an enhancement effect on the luminescence signals. Equations were derived which allow one to determine alphacyclodextrin: substrate complex stoichiometries as well as primary and secondary binding constants by using LC retention values. An equation was also derived which describes the binding of a monoprotic species in which either its ionized or unionized form could bind to one or two cyclodextrin molecules. Becaused multiple binding constants are difficult to evaluate graphically, a non-linear least squares computer program was utilized. The approach works equally well forthe determination of binding cqnstants in micellar media. Resonance enhancement of Raman signals requires excitation on an absorption band of a molecule. This frequently produces background fluorescence from which it is difficult or impossible to extract a vibrational spectrum. Carrying out the resonance Raman analysis in certain dilute aqueous micellar solutions allows one to circumvent the luminescence problem in many cases. Several difÃerent micellar effects can be used simultaneously to enhance Raman signals relative to the background. Both the laser excitation line and the micellar system must be properly chosen so as to produce the best signal to noise ratio. The first examples of micelle mediated resonance Raman analysis of fluorescent compounds using UV and visible laser excitation was shown. Obtaining resonance Raman spectra from thin-layerchromatography plates was also demonstrated.Item Separation of alkaloid isomers and stereoisomers with beta-cyclodextrin bonded phases(Texas Tech University, 1987-08) Ward, Karen DeniseNot available