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Dressman, Jennifer; Amidon, Gordon; Reppas, Christos; Shah, Vinod
doi: 10.1023/A:1011984216775pmid: 9487541
Dissolution tests are used for many purposes in the pharmaceutical industry: in the development of new products, for quality control and, to assist with the determination of bioequivalence. Recent regulatory developments such as the Biopharmaceutics Classification Scheme have highlighted the importance of dissolution in the regulation of post-approval changes and introduced the possibility of substituting dissolution tests for clinical studies in some cases. Therefore, there is a need to develop dissolution tests that better predict the in vivo performance of drug products. This could be achieved if the conditions in the gastrointestinal tract were successfully reconstructed in vitro. The aims of this article are, first, to clarify under which circumstances dissolution testing can be prognostic for in vivo performance, and second, to present physiological data relevant to the design of dissolution tests, particularly with respect to the composition, volume, flow rates and mixing patterns of the fluids in the gastrointestinal tract. Finally, brief comments are made in regard to the composition of in vitro dissolution media as well as the hydrodynamics and duration of the test.
doi: 10.1023/A:1011936300845pmid: 9487542
The common principles of molecular recognition with cooperative or bidentate hydrogen bonds, dispersion forces and hydrophobic packing govern the specificity of protein-carbohydrate interaction. Enthalpy/entropy-compensation is also valid, maintaining KD-values in the range of 30 mM to 200 nM. The individual contributions of the enthalpic and entropic factors which originate from the receptor, the ligand and/or the solvent to the overall free energy change can at least be estimated by a combination of computer-assisted molecular modeling, NMR spectroscopy of the reactants before and after complex formation and thermodynamic measurements. The delineation of adaptable parameters such as ligand or receptor side chain flexibility points to a route to practicable guidelines for a rational design of mimetics in glycosciences.
Moe, Scott; Smith, Daryl; Chien, Yongwei; Raszkiewicz, Joanna; Artman, Linda; Mueller, Alan
doi: 10.1023/A:1011988317683pmid: 9487543
Purpose. Twelve synthetic spider toxin analogs were prepared in an effort to better understand the structure-activity relationships of the polyamine portion of argiotoxin-636 (Arg-636), a noncompetitive NMDA receptor (NMDAR) antagonist.
Hsieh, Hsin-Kaw; Lee, Tai-Hua; Wang, Jih-Pyang; Wang, Jeh-Jeng; Lin, Chun-Nan
doi: 10.1023/A:1011940401754pmid: 9487544
Purpose. Mast cell and neutrophil degradations are the important players in inflammatory disorders. Combined with potent inhibition of chemical mediators released from mast cells and neutrophil degranulations, it could be a promising anti-inflammatory agent. 2′,5′-Dihydroxychalcone has been reported as a potent chemical mediator and cyclooxygenase inhibitor. In an effort to continually develop potent anti-inflammatory agents, a novel series of chalcone, 2′- and 3′-hydroxychalcones, 2′,5′-dihydroxychalcones and flavanones were continually synthesized to evaluate their inhibitory effects on the activation of mast cells and neutrophils and the inhibitory effect on phlogist-induced hind-paw edema in mice.
doi: 10.1023/A:1011992518592pmid: 9487545
Purpose. This study aims to assess the drug absorption kinetics of three drugs and compare their resulting first-order intestinal permeation rate constants to their Caco-2 monolayer permeabilities.
Gan, Liang-Shang; Yanni, Souzan; Thakker, Dhiren
doi: 10.1023/A:1011944602662pmid: 9487546
Purpose. The tight junctions in the intestinal epithelium represent highly specialized intercellular junctions. Ranitidine, an H2-antagonist, causes a tightening of the tight junctions. Hence, we have investigated the effect of ranitidine and other H2-antagonists on the function of the intestinal tight junctions.
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