Sanjeev Kumar

This research has focused on the incorporation of the thiadiazole moiety into versatile pyridine ring because of their biological properties. In order to explore the possibilities of some altered biological action author envisaged that by designing the Schiff base derivatives of 1, 3, 4-thiadiazole moiety may exhibit anticancer properties. These novel 1,3,4-thiadiazole Schiff base compounds have been synthesized by microwave-assisted synthesis and screened for their cytotoxicity on HeLa, HepG2 and MCF7 cancer cell lines.The key intermediate 2-(4-fluorophenyl)pyridine-3-carboxylic acid was obtained by hydrolysing the ester 3 in presence of KOH and methanol.Thus obtained compound 4 was treated with thiosemicarbazide and phosphorous oxychloride and cyclized in microwave inorder to get the intermediate 5-[2-(4-fluorophenyl) pyridin-3-yl]-1, 3, 4-thiadiazol-2-amine. The amine 5 was reacted with different aldehydes (a-h) in presence of catalytic amount of acetic acid and obtaineda series of novel Schiff base derivatives 6a-6h. These compounds were characterized by MS, 1H-NMR,IR and elemental analysis. Most of the compounds in this series have exhibited moderate cytotoxicity onall the three human cell lines at different concentrations, but two compounds 6f and 6h showed good inhibition towards liver carcinoma cell lines having IC50 of 23.8µMand 13.4µM respectively.

Poor aqueous solubility of drugs is a major limiting factor with many new drugs in their successful launch in market in spite of their potential pharmacokinetic activity. Poorly water soluble drugs are becoming a problem in terms of obtaining satisfactory dissolution within the gastro intestinal tract, which is necessary for good bioavailability. Poorly water-soluble drugs are associated with slow drug dissolution followed by slow absorption leading eventually to inadequate and variable bioavailability. Various approaches to overcome the poor aqueous solubility of drugs have been investigated like solid dispersion, spherical agglomeration, nanoparticles, nanosuspensions, nanomorphs, nanocrystals, micronization, polymorphism, co-solvency, pH adjustment, use of surfactants, microemulsion, complexation. In this article, the basic approaches for enhancement of solubility and dissolution of poorly water-soluble drugs have been reviewed with literature-based examples of the formulation options for poorly water-soluble compounds and their practical applications to the industrial practices.

This study investigated the spherical agglomeration of itraconazole for enhanced drug dissolution rate and bioavailability at various polymers percentage like 0.2%, 0.4%and 0.6% with Soluplus®, HPMC and PEG-4000 by simple stirring at 900 r.p.m. (The spherical agglomerates(SA) were dried powdered and with method followed by characterized by differential scanning calorimetry and X-ray powder diffraction. The SAs of itraconazole were also evaluated by drug content study, solubility study and in-vitro dissolution study. The pharmacokinetic studies of the formulations and pure itraconazole were evaluated i.e. Cmax, Tmax and AUC   in vivo study by pharmacokinetic model on wistar rats.