L'Auto-vélo : automobilisme, cyclisme, athlétisme, yachting, aérostation, escrime, hippisme / dir. Henri Desgranges

07 mai 19171917/05/07 (A18,N5950)

Anesthetic behavioral changes of <i>Cyprinus carpio</i> exposed to 100, 200, 300, and 400 mg/L of AGO in SMEDDS-AGO and NE-AGO-D in comparison with EtOH-AGO.

<p>The dataset is available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188848#pone.0188848.s005" target="_blank">S5 Dataset</a>.</p

Effect of pressure and number of homogenization cycles on droplet size of the best NE-AGO formulation (NE-AGO-D).

<p>Data are presented as means ± S.E.M. (<i>p</i> <0.05). Asterisks (*) indicate a significant difference between the obtained NE-AGO-D after using a pressure of 5,000 and 10,000 psi (<i>p</i> <0.05). The dataset is available in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188848#pone.0188848.s001" target="_blank">S1 Dataset</a>.</p

Amino Acids as Co-amorphous Excipients for Simvastatin and Glibenclamide: Physical Properties and Stability

Co-amorphous drug mixtures with low-molecular-weight excipients have recently been shown to be a promising approach for stabilization of amorphous drugs and thus to be an alternative to the traditional amorphous solid dispersion approach using polymers. However, the previous studies are limited to a few drugs and amino acids. To facilitate the rational selection of amino acids, the practical importance of the amino acid coming from the biological target site of the drug (and associated intermolecular interactions) needs to be established. In the present study, the formation of co-amorphous systems using cryomilling and combinations of two poorly water-soluble drugs (simvastatin and glibenclamide) with the amino acids aspartic acid, lysine, serine, and threonine was investigated. Solid-state characterization with X-ray powder diffraction, differential scanning calorimetry, and Fourier-transform infrared spectroscopy revealed that the 1:1 molar combinations simvastatin–lysine, glibenclamide–serine, and glibenclamide–threonine and the 1:1:1 molar combination glibenclamide–serine–threonine formed co-amorphous mixtures. These were homogeneous single-phase blends with weak intermolecular interactions in the mixtures. Interestingly, a favorable effect by the excipients on the tautomerism of amorphous glibenclamide in the co-amorphous blends was seen, as the formation of the thermodynamically less stable imidic acid tautomer of glibenclamide was suppressed compared to that of the pure amorphous drug. Furthermore, the co-amorphous mixtures provided a physical stability advantage over the amorphous drugs alone

Chemical composition of AGO.

<p>Chemical composition of AGO.</p

Characterization of NE-AGO.

<p>Characterization of NE-AGO.</p

Investigation of the Intra- and Interlaboratory Reproducibility of a Small Scale Standardized Supersaturation and Precipitation Method

The high number of poorly water-soluble compounds in drug development has increased the need for enabling formulations to improve oral bioavailability. One frequently applied approach is to induce supersaturation at the absorptive site, e.g., the small intestine, increasing the amount of dissolved compound available for absorption. However, due to the stochastic nature of nucleation, supersaturating drug delivery systems may lead to inter- and intrapersonal variability. The ability to define a feasible range with respect to the supersaturation level is a crucial factor for a successful formulation. Therefore, an <i>in vitro</i> method is needed, from where the ability of a compound to supersaturate can be defined in a reproducible way. Hence, this study investigates the reproducibility of an <i>in vitro</i> small scale standardized supersaturation and precipitation method (SSPM). First an intralaboratory reproducibility study of felodipine was conducted, after which seven partners contributed with data for three model compounds; aprepitant, felodipine, and fenofibrate, to determine the interlaboratory reproducibility of the SSPM. The first part of the SSPM determines the apparent degrees of supersaturation (aDS) to investigate for each compound. Each partner independently determined the maximum possible aDS and induced 100, 87.5, 75, and 50% of their determined maximum possible aDS in the SSPM. The concentration–time profile of the supersaturation and following precipitation was obtained in order to determine the induction time (<i>t</i>_ind) for detectable precipitation. The data showed that the absolute values of <i>t</i>_ind and aDS were not directly comparable between partners, however, upon linearization of the data a reproducible rank ordering of the three model compounds was obtained based on the β-value, which was defined as the slope of the ln­(<i>t</i>_ind) versus ln­(aDS)⁻² plot. Linear regression of this plot showed that aprepitant had the highest β-value, 15.1, while felodipine and fenofibrate had comparable β-values, 4.0 and 4.3, respectively. Of the five partners contributing with full data sets, 80% could obtain the same rank order for the three model compounds using the SSPM (aprepitant > felodipine ≈ fenofibrate). The α-value is dependent on the experimental setup and can be used as a parameter to evaluate the uniformity of the data set. This study indicated that the SSPM was able to obtain the same rank order of the β-value between partners and, thus, that the SSPM may be used to classify compounds depending on their supersaturation propensity