Rhodium-catalyzed decomposition of fused bicyclic α-diazo-β-hydroxyketones results in good yields of bridged bicyclo[m.n.1]ketones via a rearrangement pathway.
Formulating pharmaceutical cocrystals as inhalable dosage forms represents a unique niche in effective management of respiratory infections. Favipiravir, a broad-spectrum antiviral drug with potential pharmacological activity against SARS-CoV-2, exhibits a low aqueous solubility. An ultra-high oral dose is essential, causing low patient compliance. This study reports a Quality-by-Design (QbD)-guided development of a carrier-free inhalable dry powder formulation containing a 1:1 favipiravir–theophylline (FAV-THP) cocrystal via spray drying, which may provide an alternative treatment strategy for individuals with concomitant influenza infections and chronic obstructive pulmonary disease/asthma. The cocrystal formation was confirmed by single crystal X-ray diffraction, powder X-ray diffraction, and the construction of a temperature–composition phase diagram. A three-factor, two-level, full factorial design was employed to produce the optimized formulation and study the impact of critical processing parameters on the resulting median mass aerodynamic diameter (MMAD), fine particle fraction (FPF), and crystallinity of the spray-dried FAV-THP cocrystal. In general, a lower solute concentration and feed pump rate resulted in a smaller MMAD with a higher FPF. The optimized formulation (F1) demonstrated an MMAD of 2.93 μm and an FPF of 79.3%, suitable for deep lung delivery with no in vitro cytotoxicity observed in A549 cells.
Maintenance of sewage treatment systems is useful to identify dead septic tanks and to determine the cause, which is often heavy use of detergent with bleach or heavy disinfectant use in general. When detergent without bleach is substituted, treatment typically recovers completely. A field experiment to quantify the effects of household chemicals was carried out using lowstrength wastewater dosed at a diurnal rate to four 100 L pilot-scale septic tanks and calibrated to four-day residence time. Mixtures of detergent with bleach and bleach pucks were used, with dose concentrations calibrated to tank size and to laundry or toilet volumes. After a one-week start-up period, chemicals were dosed for 2 weeks, stopped for 2 weeks (by accident), and started again for 4 weeks, followed by 2 weeks of no chemicals. The experimental run was divided into two sets, Set A with no chemicals dosed and Set B with chemicals dosed. Average %BOD removals were calculated at each sampling day and a "paired t-test" was employed to compare the significance of the differences between Tests and the Control for each set. The paired t-test on BOD removal rates showed that for Set A (no chemicals dosed) there were significant differences between the pilot-scale septic tanks receiving detergent (ST-1-75% poorer removal efficiency) and BOTH chemicals (ST-4-71% poorer removal efficiency) at the 95% confidence level, primarily due to the divergent effluent BOD concentrations found at the beginning of the experimental run. Towards the end of the experimental run, after chemical dosing is ceased, all pilot-scale septic tanks seemed to perform equally indicating that septic tanks recover quite readily. ST-3 receiving flush puck solution (29% poorer removal efficiency) showed no significant difference compared to the control. The paired t-test for Set B showed that the differences between ST-1 (88% poorer removal efficiency) and ST-4 (200% poorer removal efficiency) compared to the Control were significant at the 95% confidence level. The addition of flush puck solution (ST-3) seemed to actually improve %BOD removal (31% higher removal efficiency), but the difference was not statistically significant compared to the Control. Fecal Coliforms were typically lower than the Control, but not diagnostic, suggesting no widespread 'kills' at these levels of chemical addition. Dead septic tanks are caused by greater use of disinfectants than used in this experiment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.