Harrellhjort3267

The concept of using precipitation inhibitors (PIs) to sustain supersaturation is well established for amorphous formulations but less in the case of lipid-based formulations (LBF). This study applied a systematic in silico-in vitro-in vivo approach to assess the merits of incorporating PIs in supersaturated LBFs (sLBF) using the model drug venetoclax. sLBFs containing hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyvinylpyrrolidone (PVP), PVP-co-vinyl acetate (PVP/VA), Pluronic F108, and Eudragit EPO were assessed in silico calculating a drug-excipient mixing enthalpy, in vitro using a PI solvent shift test, and finally, bioavailability was assessed in vivo in landrace pigs. The estimation of pure interaction enthalpies of the drug and the excipient was deemed useful in determining the most promising PIs for venetoclax. The sLBF alone (i.e., no PI present) displayed a high initial drug concentration in the aqueous phase during in vitro screening. sLBF with Pluronic F108 displayed the highest venetoclax concentration in the aqueous phase and sLBF with Eudragit EPO the lowest. In vivo, the sLBF alone showed the highest bioavailability of 26.3 ± 14.2%. Interestingly, a trend toward a decreasing bioavailability was observed for sLBF containing PIs, with PVP/VA being significantly lower compared to sLBF alone. In conclusion, the ability of a sLBF to generate supersaturated concentrations of venetoclax in vitro was translated into increased absorption in vivo. While in silico and in vitro PI screening suggested benefits in terms of prolonged supersaturation, the addition of a PI did not increase in vivo bioavailability. The findings of this study are of particular relevance to pre-clinical drug development, where the high in vivo exposure of venetoclax was achieved using a sLBF approach, and despite the perceived risk of drug precipitation from a sLBF, including a PI may not be merited in all cases.The superhydrophobic surface has been used in ultradry surface applications, such as the maritime industry, windshields, non-sticky surfaces, anti-icing surfaces, self-cleaning surfaces, and so forth. However, one of the main hurdles for the production of superhydrophobic surfaces is high-cost fabrication methods. Here, we report a handy process of self-synthesis fabrication of superhydrophobic surfaces with daily supplies. Driven by the physics of biscuit dunking, we introduce a method to self-synthesize superhydrophobic surfaces from daily supplies by coating a substrate with a liquid (liquids of paraffin from candles or polydimethylsiloxane) and subsequently sprinkling powders (food-desiccant silica, alumina, sugar, salt, or flour). A mechanistic study revealed that the capillary force, governed by surface energy difference, liquid viscosity, and powder pore size, draws the liquid solution into the porous channels within the powders. The entire surface of powders, in turn, is covered with the low-surface-energy liquid to maintain the porosity, creating a 3D porous nanostructure, resulting in a water contact angle over 160°. This work provides a scientific understanding that technological developments are closely related to the science that can be seen in our daily lives. Also, we believe that further intensive studies extended from this work could enable to home-fabricate a superhydrophobic surface, such as a bathtub and sink in bathrooms and a cooking area and sink in kitchens.Click reactions (e.g., Huisgen cycloaddition) on metal oxide nanostructures offer a versatile and robust surface molecular modification for various applications because they form strong covalent bonds in a wide range of molecular substrates. This study reports a rational strategy to maximize the conversion rate of surface click reactions on single-crystalline ZnO nanowires by monitoring the reaction progress. p-Polarized multiple-angle incidence resolution spectrometry (pMAIRS) and Fourier-transformed infrared (FT-IR) spectroscopy were employed to monitor the reaction progress of an azide-terminated self-assembled monolayer (SAM) on single-crystalline ZnO nanowires. Although various reaction parameters including the concentration of Cu(I) catalysts, triazolyl ligands, solvents, and target alkynes were systematically examined for the surface click reactions, 10-30% of terminal azide on the nanowire surface remained unreacted. selleck chemicals Temperature-dependent FT-IR measurements revealed that such unreacted residual azides deteriorate the thermal stability of the nanowire molecular layer. To overcome this observed conversion limitation of click reactions on nanostructure surfaces, we considered the steric hindrance around the closely packed SAM reaction points, then experimented with dispersing the azide moiety into a methyl-terminated SAM. The mixed-SAM method significantly improved the azide conversion rate to almost 100%. This reaction method enables the construction of spatially patterned molecular surface modifications on metal oxide nanowire arrays without detrimental unreacted azide groups.Herein, we disclose a unique directing effect of 9-substituted triptycenes in electrophilic substitution to achieve the regioselective functionalization of the triptycene core. The Hirshfeld population analysis was adopted to predict the selectivity in electrophilic substitution. TMS and t-Bu groups were found to considerably accelerate the reaction at C2 positions to produce C3-symmetric isomers. Correlation between distortion and charge distribution within benzene rings was systematically examined.An enantioselective allylation of silyl-substituted acetylenic aldehydes by chiral phosphoric acid (CPA)/transition metal cooperative catalysis was developed. Enantioenriched homoallylic propargyl alcohols were obtained in good yields with excellent enantioselectivities (>99% ee) under mild conditions. Moreover, the shortest formal synthesis of fostriecin was achieved by the present enantioselective allylation protocol as the key step. The known intermediate of fostriecin reported by McDonald and co-worker was synthesized in only nine steps in 39% total yield.