Quabodepistat (OPC-167832), a Novel Antituberculosis Drug Candidate: Enhancing Oral Bioavailability via Cocrystallization and Mechanistic Analysis of Bioavailability in Two Cocrystals.

Quabodepistat (code name OPC-167832) is a novel antituberculosis drug candidate. This study aimed to discover cocrystals that improve oral bioavailability and to elucidate the mechanistic differences underlying the bioavailability of different cocrystals. Screening yielded two cocrystals containing 2,5-dihydroxybenzoic acid (2,5DHBA) or 2-hydroxybenzoic acid (2HBA).

Crystal structure of a 1:1 co-crystal of quabodepistat (OPC-167832) with 2,5-di-hydroxy-benzoic acid using microcrystal electron diffraction.

Quabodepistat [(5-{[(3,4)-1-(4-chloro-2,6-di-fluoro-phen-yl)-3,4-di-hydroxy-piperidin-4-yl]meth-oxy}-8-fluoro-3,4-di-hydro-quinolin-2(1)-one); CHClFNO] and 2,5-di-hydroxy-benzoic acid (2,5DHBA; CHO) were successfully co-crystallized. Given the small size of the crystals (1 × 0.2 × 0.

Four Novel Pharmaceutical Cocrystals of Oxyresveratrol, Including a 2 : 3 Cocrystal with Betaine.

Cocrystal engineering can alter the physicochemical properties of a drug and generate a superior drug candidate for formulation design. Oxyresveratrol (ORV) exhibits a poor solubility in aqueous environments, thereby resulting in a poor bioavailability. Extensive cocrystal screening of ORV with 67 cocrystal formers (coformers) bearing various functional groups was therefore conducted using grinding, liquid-assisted grinding, solvent evaporation, and slurry methods.

Sodium Nitroprusside Enhances Absorption in the Rat Jejunum via the Transcellular Route.

It was reported that nitric oxide (NO) donors increased the permeability of water-soluble compounds across intestinal membrane with neither loss of cell viability nor release of lactate dehydrogenase. Therefore, the detail mechanism of action of NO donors on the gastrointestinal membrane has yet to be clarified. We previously reported the possibility of the enhancing effect of the NO donor on the membrane permeability via transcellular route.

Effects of pharmaceutical excipients on membrane permeability in rat small intestine.

Pharmaceutical excipients should not disturb the effects of drug therapy. In recent years, however, it has been reported that excipients induce some changes to the tight junction (TJ) and P-glycoprotein (P-gp), which can affect drug disposition. In this study, we examined the effects of 20 common pharmaceutical excipients from different classes on mucosal membrane and the differences of such effects among regions of the small intestine.