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Graphical abstract Abstract CKD-519, a potent cholesteryl ester transfer protein (CETP) inhibitor, is a clinical candidate being developed for the treatment of dyslipidemia. It is considered a Biopharmaceutical Classification System II compound with low solubility and high permeability. The objective of this study was to develop early formulations focusing on the dissolution rate of the compound to achieve dose-dependent exposure. High performance formulation strategies including solid dispersion (SD) and a self-microemulsifying drug delivery system (SMEDDS) were investigated and their in vivo and in vitro correlations were also evaluated in monkeys along with dose optimization in human volunteers. The SD granules were prepared in a fluid bed granulator using microcrystalline cellulose and mannitol as carriers. Poloxamer 407 and Eudragit E PO were each found to be a suitable solubilizing agent and polymer for the improvement of the CKD-519 dissolution rate. Pharmacokinetic studies in monkeys showed that the SD tablets exhibited better absorption than the SMEDDS in a dose-dependent manner from 1.5 mg to 100 mg. The mannitol-based SD tablet formulations were bioequivalent. However, pharmacokinetics studies in humans showed that the dose was saturable above 100 mg of CKD-519. This study was performed to determine how to develop early formulations for clinical studies and to identify rational formulation development strategies for CKD-519 to establish the pharmaceutical proof-of-concept in humans. [ABSTRACT FROM AUTHOR]

Abstract: Nuclear magnetic resonance (NMR) techniques coupled with multivariate data analysis were used to conduct monitoring of biochemical changes of black raspberry fruits at different stages of maturation and under various extraction and NMR dissolution solvent conditions: extraction with 50% methanol and D2O as an NMR dissolution solvent, extraction with 50% methanol and 50% methanol-d 4 as an NMR dissolution solvent, and extraction with 100% ethyl acetate and 100% methanol-d 4 as an NMR dissolution solvent. Partial least-squares discriminant analysis reliably distinguished black raspberry fruits according to the maturation stage, whereby the relative levels of various compounds such as amino acids, organic acids, sugars and phenolic compounds were compared using analysis of variance. Sucrose and most of the amino acids, and organic acids decreased, whereas fructose, glucose, and cyanidins increased in relative concentration according to maturation of black raspberry fruits. The total number and kinds of assigned compounds of the three solvent systems were also compared. This research demonstrates that the metabolic profile of black raspberry fruits changes during maturation, and provides objective criteria for determining the stage of black raspberry fruit maturation via a 1H NMR-based metabolomics technique using multiple solvent systems. [Copyright &y& Elsevier]

Abstract: The effect of administration of Korean black raspberry (BR) to smokers was assessed by 1H nuclear magnetic resonance (NMR) coupled with multivariate statistical analysis. In this study, to investigate the effect of BR on the level of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), biomarker for DNA damage, 38 male smokers between 20 and 30years old were treated with BR or placebo for 4weeks. After 4weeks of administration, urinary level of 8-OHdG was measured, and the metabolic profiling of plasma samples of all volunteers were established using 1H NMR-based metabolomics techniques. The volunteers of BR administered group were divided into responder group (BR-R group) and nonresponder group (BR-NR group) based on the mean decrement of urinary 8-OHdG level of placebo group (12%). There was a clear separation among weeks 0 and 4 of seven volunteers at BR-R group in principal component analysis (PCA) derived score plots. The levels of 16 metabolites including amino acids, and organic acids changed significantly between weeks 0 and 4. Then the comparative metabolic profiling of the BR-R and BR-NR groups at week 0 was performed. There was also clear separation in PCA-derived score plot. The relative levels of glycine and trimethylamine N-oxide in plasma changed significantly between the two groups, indicating that these compounds could be used as screening biomarkers to predict the 8-OHdG modulating activity of BR in smokers. [Copyright &y& Elsevier]

The biological treatment of a tri-component mixed waste gas system in BRC1 and BRC2 biofilters packed with rock wool-compost media was studied. The model gases were NH3, H2S and toluene. The gases were fed initially at about 50–55ppm each. H2S was found to have the shortest start-up while toluene had the longest. Under two different NH3:H2S:toluene concentration ratios of 250:120:55 and 120:220:55 (in ppm) for BRC1 and BRC2, the removal efficiencies of NH3, H2S and toluene were found to be affected by their respective loading rate. On the other hand, toluene removal was observed to be inhibited at H2S concentration of 220ppm as well. Almost complete removal of NH3 and H2S was achieved when loading rate was applied up to 16.14g-NH3/(m3 bedh) and 36.09g-H2S/(m3 bedh), respectively. The maximum elimination capacity for NH3 was determined to be 23.67g-NH3/(m3 bedh) at 78.6% removal efficiency and for H2S, 38.50g-H2S/(m3 bedh) at 68.1% removal efficiency. The maximum toluene elimination capacity was 30.75g-toluene/(m3 bedh) at 87.9% removal efficiency when the concentration of NH3:H2S:toluene was 250:120:55 in BRC1, and was 16.60g-toluene/(m3 bedh) at 45.5% removal efficiency when the concentration of NH3:H2S:toluene was 120:220:55 in BRC2. The pressure drops along both columns were low and the ratio of bed compactions over biofilter height was observed to be less than 0.02. [Copyright &y& Elsevier]