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Sorafenib, a potent anticancer drug, has low absorption in the gastrointestinal tract due to its poor aqueous solubility. The main purpose of this investigation was to design sorafenib nanoparticle using a newly developed technique, nanoparticulation using fat and supercritical fluid (NUFS™) to improve the absorption of sorafenib. The quality by design (QbD) tool was adopted to define the optimal formulation variables: hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone K30 (PVP), and poloxamer. The studied response variables were particle size of nanoparticle, dissolution (5, 60, and 180 min), drug concentration time profile of nanoparticle formulations, and maximum drug concentration. The result of particle size revealed that an increase in concentration of poloxamer and HPMC decreased the particle size of nanoparticles (p 0.05). Likewise, the concentration of drug release at different time point (5, 60, and 180 min) showed HPMC and poloxamer had positive effects on drug dissolution while PVP had negative effects on it. The design space was built in accordance with the particle size of nanoparticle (target 500 nm) and dissolution of sorafenib (target 7 µm/mL), following failure probability analysis using Monte Carlo simulations. In vivo pharmacokinetics studies in beagle dogs demonstrated that optimized formulation of sorafenib (F3 and F4 tablets) exhibited higher blood drug profiles indicating better absorption compared to the reference tablet (Nexavar

Central nervous system (CNS) metastasis is one of the serious complications of epidermal growth factor receptor (EGFR)‐mutant lung cancer, which arises due to poor penetration of the brain–blood barrier by EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). Although osimertinib, a third‐generation EGFR‐TKI, has efficacy against CNS metastases, further treatment modalities are still needed as some of these lesions do not respond to osimertinib, or undergo progression after an initial response to this drug if radiotherapy has already been conducted. Here, we investigated the efficacy of water‐soluble erlotinib (NUFS‐sErt) against these metastases. This agent was synthesized using a nano‐particulation platform technology utilizing fat and supercritical fluid (NUFS™) to resolve the low solubility problem that typically prevents the creation of injectable forms of EGFR‐TKIs. The average NUFS‐sErt particle size was 236.4 nm, and it showed time‐dependent dissolution in culture media. The effects of NUFS‐sErt were similar to those of conventional erlotinib in terms of inhibiting the proliferation of EGFR‐mutant lung cancer cells and suppressing EGFR signaling. In an intraperitoneal xenograft model of HCC827 cells, intraperitoneal administration of NUFS‐sErt produced a dose‐dependent inhibition of tumor growth and enhanced survival rate. Notably, the injection of NUFS‐sErt into the brain ventricle caused significant tumor growth inhibition in an intracranial xenograft model. Hence, our current findings indicate that NUFS‐sErt is a novel, water‐soluble form of erlotinib that can be administered using intraventricular or intrathecal injections. The target cases would be patients with a progressive CNS metastasis and no other therapeutic options. This drug could also be given intravenously to patients with swallowing difficulties or an inability to ingest due to a medical condition.

For alkali metal cation sensing in aqueous dioxane solution, a novel dibenzo-16-crown-5 (DB16C5) fluoroionophore 1, N-(pyren-1-yl)-sym-(propyl)dibenzo-16-crown-5-oxyacetamide, has been synthesized. Examination of fluorescent behavior for 1 in 4∶1 1,4-dioxane–water (v/v) containing tetramethylammonium hydroxide (TMAOH) reveals that proton dissociation of the carboxamido moiety is promoted by Na+ binding, which results in an emission ratio response due to internal charge transfer (ICT) from the donor carboxamido anion to the pyrene acceptor. The emission intensity ratio (I459/I387) increases with enhancement of the Na+ concentration. No fluorescent response is induced by the presence of Li+, K+, or Cs+. This high Na+ selectivity is attributed to a preorganized structure of DB16C5 lariat ether binding site in which Na+ binds tightly to the carbonyl oxygen of the side arm to induce selective proton dissociation. Thus a ratiometric emission response with high Na+ selectivity has been obtained for 1 in 4∶1 1,4-dioxane–water (v/v) containing TMAOH.

α-Iodoketones are prepared in high yields from the initial reaction of various ketones with HNIB in CH3CN and subsequent treatment of potassium iodide or samarium(II) iodide.

Treatment of ketones with thallium(III) triflate in amide solvents at 60 °C for 30 min followed by addition of small amounts of H2O cleanly provided the corresponding α-acyloxy ketones.

Treatment of ketones with thallium(III) triflate in amide solvents at 60 °C for 30 min followed by addition of small amounts of H2O cleanly provided the corresponding α-acyloxy ketones.