Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine

A novel, pH-responsive supramolecular graft copolymeric micelle, composed of dextran and poly (oleic acid), has been synthesized through reversible addition fragmentation chain transfer polymerization with controlled M_n and narrow polydispersity. The structural properties of the copolymer have been studied using FTIR and ¹H NMR spectral analyses. Critical micelle concentration (CMC) has been determined fluorometrically and conductometrically. The copolymer shows pH responsive micellar stability, which has been confirmed using DLS study. Dextran-g-OA copolymer demonstrates spherical morphology at CMC, while rod-like assembly has been evidenced beyond CMC that is probably because of the structural alteration of copolymeric chains at higher copolymer concentration. Dextran-g-OA is noncytotoxic toward MG-63 cells. As the self-assemble nature of copolymer micelle promotes the oral administration of hydrophobic drugs, nifedipine (NFD, a hydrophobic drug) has been used as model drug that has been encapsulated substantially into the core of the micelle. The copolymer releases the loaded NFD at a much slower rate in simulated gastric fluid (pH 1.2) and relatively faster in simulated intestinal fluid (pH 7.4) with a cumulative release of ~95% within 24 h, suggesting an ideal candidate as nifedipine carrier. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2354–2363     

Synthesis,Characterization and Properties of Two Novel E - and Z -Stilbenophanes: Their Lithium-selective Complexation and C-H⋯O Short Hydrogen Bonds in the X-ray Structure of the E -Isomer

Stilbenophanes 1c and 2c were synthesized in good yields. Among alkali ions, both isomers only formed 1:1 complexes with lithium selectively. An X-ray structure of 1c shows a statistical disorder which leads to two refined positions for the ethylene moiety. The existence of a weak intramolecular C-H > O hydrogen bond in its structure was confirmed by both X-ray analysis and theoretical calculation.     

A New Route to 3-Phenoxybenzyl cis (±) 2,2-Dimethyl-3-(2-Phenyl-2-Chlorovinyl) Cyclopropanecarboxylate

Synthetic pyrethroids belong to an almost ideal group of modern insecticides due to their high insecticidal activity, low mammalian toxicity and rapid biodegradability.¹ While several pyrethroids with potent insecticidal action have been synthesized, search for analogues with high photostability and other pesticidal activity continues. In this connection some esters of 2,2-dimethyl-3-(2-phenyl-2-chlorovinyl) cyclopropane-carboxylic acid have recently been reported to have good acaricidal activity^2–4 as well. Structure-activity relationship reveals that for the synthetic pyrethroids, esters of cis-substituted cyclopropanecarboxylic acid show far superior activity compared to the corresponding trans-isomer. Most of the methods described in the literature⁵ lead to a mixture of cis and trans-substituted cyclopropanecarboxylic acids.     

Solid State Regeneration of Ketones From Semicarbazones Using Antimony Trichloride Under Microwave Irradiation

Microwave irradiation of ketosemicarbazones with wet antimony trichloride under solvent-free condition provides a fast, efficient and simple method for the regeneration of ketones in good yields.     

A New Novel and Practical One Pot Methodology for Conversion of Alcohols to Amines

A convenient and efficient one pot sequence has been developed for the transformation of alcohols to amines using Sodium azide, triphenylphosphine in CC1₄-DMF.     

Homoleptic Ti[ONO]2 type complexes of amino-acid-tethered phenolato Schiff-base ligands: Synthesis,characterization, time-resolved fluorescence spectroscopy,and cytotoxicity against ovarian and colon cancer cells

Six homoleptic Ti (IV) compounds of dianionic tridentate ONO Schiff base ligands with various substitutions were prepared from chiral amino acids, 2-hydroxybenzaldehyde, which were generated in situ, and Ti (OⁱPr)₄. The compounds were spectroscopically characterized and the molecular geometries of five complexes were established by X-ray crystallography; for two structures, two independent molecules compose the asymmetric units. The di-anionic, tridentate ligands coordinate the titanium centers via the carboxylate-O-, imine-N- and phenoxide-O atoms to form five- and six-membered chelate rings. The molecules are based on a trans-N₂O₄ donor with each carboxylate-O atom trans to a phenoxide-O atom. For the smallest derivative with Me substitution, racemization occurs during repeated recrystallization. Photophysical profiles of the titanium compounds in the solid phase and in solution are discussed. Marked cytotoxicities were recorded toward human ovarian A2780 and colon HT-29 cancer cells with IC₅₀ values ranging between 23 ± 2 and 103 ± 3 μM. Comparative hydrolytic stability of the complexes were studied by NMR in 10% D₂O solutions which provided t_1/2 values of up to 15 ± 2 hr.     

Thermogravimetric,differential scanning calorimetric,and experimental thermal transport study of functionalized nanokaolinite-doped elastomeric nanocomposites

A simple technique to synthesize and functionalize kaolinite nanoparticles having analogous shape and size in single step using layered silicate microclay as starting material is presented. The morphology, composition, and functionalization study of the activated nanokaolinite were determined by scanning electron microscopy/energy-dispersive spectroscopy, atomic-force microscope, and Fourier transform infrared spectroscopy, correspondingly. Various concentrations of activated nanokaolinite were doped in acrylonitrile butadiene rubber (NBR) by conventional industrial elastomeric mixing techniques to fabricate composite specimens. The accumulated data simulated that the thermal conductivity was diminished 92 % by increasing 15 mass% filler loading in the polymer matrix. Thermogravimetric analyzer showed that thermal stability and heat-absorbing capability were remarkably augmented by increasing activated nanokaolinite concentration in the NBR base formulation. Differential scanning calorimetric study revealed that glass transition and crystallization temperatures were reduced, whereas first and second melting phase temperatures were enhanced by increasing filler-to-host matrix ratio. Tensile strength, elongation at break, and elastic modulus at 200 % elongation were remarkably improved to a level of 144, 66, and 90 %, respectively, with increasing filler-to-matrix ratio. Efficient enhancement in elastomeric hardness was also observed.     

QbD‐oriented development and validation of a bioanalytical method for nevirapine with enhanced liquid–liquid extraction and chromatographic separation

The present studies describe the systematic quality by design (QbD)‐oriented development and validation of a simple, rapid, sensitive and cost‐effective reversed‐phase HPLC bioanalytical method for nevirapine in rat plasma. Chromatographic separation was carried out on a C₁₈ column using isocratic 68:9:23% v/v elution of methanol, acetonitrile and water (pH 3, adjusted by orthophosphoric acid) at a flow rate of 1.0 mL/min using UV detection at 230 nm. A Box–Behnken design was applied for chromatographic method optimization taking mobile phase ratio, pH and flow rate as the critical method parameters (CMPs) from screening studies. Peak area, retention time, theoretical plates and peak tailing were measured as the critical analytical attributes (CAAs). Further, the bioanalytical liquid–liquid extraction process was optimized using an optimal design by selecting extraction time, centrifugation speed and temperature as the CMPs for percentage recovery of nevirapine as the CAA. The search for an optimum chromatographic solution was conducted through numerical desirability function. Validation studies performed as per the US Food and Drug Administration requirements revealed results within the acceptance limit. In a nutshell, the studies successfully demonstrate the utility of analytical QbD approach for the rational development of a bioanalytical method with enhanced chromatographic separation and recovery of nevirapine in rat plasma. Copyright © 2015 John Wiley & Sons, Ltd.