Abstract. Curcumin (Cur), one of the most widely used natural active constituents with a great variety of beneficial biological and pharmacological activities, is a practically water-insoluble substance with a short biologic half-life. The aim of this study was to develop a sustained-release solid dispersion by employing water-insoluble carrier cellulose acetate for solubility enhancement, release control, and oral bioavailability improvement of Cur. Solid dispersions were characterized by solubility, in vitro drug release, Fourier transform infrared spectroscopy, X-ray diffractometry, and differential scanning calorimetry studies. The in vivo performance was assessed by a pharmacokinetic study. Solid-state characterization techniques revealed the amorphous nature of Cur in solid dispersions. Solubility/ dissolution of Cur was enhanced in the formulations in comparison with pure drug. Sustained-release profiles of Cur from the solid dispersions were ideally controlled in vitro up to 12 h. The optimized formulation provided an improved pharmacokinetic parameter (C max =187.03 ng/ml, t max =1.95 h) in rats as compared with pure drug (C max =87.06 ng/ml, t max =0.66 h). The information from this study suggests that the developed solid dispersions successfully enhanced the solubility and sustained release of poorly water-soluble drug Cur, thus improving its oral bioavailability effectively.

A variety of 2-aryl-3-arylamino-2-alkenenitriles were converted to N-arylindole-3-carbonitriles in a one-pot manner through NBS- or NCS-mediated halogenation followed by Zn(OAc)(2)-catalyzed intramolecular cyclization. It is postulated that the process involves the formation of arylnitrenium ion intermediates, which undergo the electrophilic aromatic substitution to give the cyclized N-arylindole product.

A variety of functionalized N-amino-3-nitrile-indole derivatives are obtained via an intramolecular hetero-cyclization of 2-aryl-3-substituted hydrazono-alkylnitriles using FeBr(3) as a single electron oxidant. This approach allows the N-moiety on the side-chain to be annulated to the benzene ring during the final synthetic step via direct oxidative aromatic C-N bond formation.

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