Preparation and characterization of floating drug delivery system of azithromycin.

The objective of present study was to develop a stomach drug delivery system of azithromycin (AZH) as a model drug for eradication of Helicobacter pyloni (H. pylori). Floating microspheres of AZH were prepared by the solvent evaporation method. The prepared microspheres were subjected to evaluation for particle size, incorporation efficiency, in vitro buoyancy and in vitro drug release characteristics. The formulations were prepared at a variable stirring rate (300 to 500 rpm) and temperature (30-50 degrees C). Surface morphology characteristics were studied using scanning electron microscopy (SEM). The mean particle size of the microspheres significantly increased with increasing polymer concentration and was in the range 252.26 +/- 6.50 to 380.91 +/- 4.59 microm. Angle of repose was between 26.42 to 35.83 degrees. Tapped density ranged between 0.493 to 0.612 g/cm3. The compressibility index of all formulations was found to be in the range of 12.41 to 17.16%, which was < 20 indicating good flow characteristics. The encapsulation efficiency of the prepared microspheres was in the range of 27.8 +/- 4.30 to 66.23 +/- 2.08%. The physical state of the drug, before and after formulation was determined by differential scanning calorimetry (DSC). Percentage buoyancy of the microspheres was in the range 45.52 +/- 0.69 to 68.71 +/- 0.61% for 8 h. In vitro drug release studies were performed in simulated gastrointestinal fluid (SGF), pH 2.0 as dissolution medium (900 mL) for 8 h. Effects of stirring rate during preparation, polymer concentration and temperature on the size of microspheres and drug release were also observed. The results of the present studies indicated that the floating microspheres of AZH were formulated to provide site specific delivery of drug with a view to provide an effective and safe therapy for eradication of H. pylori with a reduced dose and reduced duration of therapy.

Synthesis and antiepileptic activity of some novel semicarbazones containing 1,3,4-thiadiazole and quinazoline ring.

The incomplete seizure control with frequent adverse effects of current anticonvulsant drugs and the importance of semicarbazones, quinazolines and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore prompted us to carry out synthesis of three novel series of semicarbazones containing 1,3,4-thiadiazole and quinazoline ring. The chemical structures of these compounds were elucidated by elemental and spectral (IR, 1H NMR, 13C NMR and MS) analysis. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The rotorod test was conducted to evaluate neurotoxicity. The majority of the compounds were found active in the biological screening. The outcome of the present investigations proved that the four binding sites pharmacophore model is decisive for antiepileptic activity. An attempt has also been performed to establish structure-activity relationships among synthesized compounds.

2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors.

The enzymatic inhibition of histone deacetylase activity has come out as a novel and effectual means for the treatment of cancer. Two novel series of 2-[5-(4-substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino]-pyrimidine-5-carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized as novel hydroxamic acid based histone deacetylase inhibitors. The antiproliferative activities of the compounds were investigated in vitro using histone deacetylase inhibitory assay and MTT assay. The synthesized compounds were also tested for antitumor activity against Ehrlich ascites carcinoma cells in Swiss albino mice. The efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid based histone deacetylase inhibitor.

Appraisal of GABA and PABA as linker: design and synthesis of novel benzamide based histone deacetylase inhibitors.

Histone deacetylase inhibitors have been actively explored as a new generation of chemotherapeutics for cancers, generally known as epigenetic therapeutics. Two novel series of N-(2-amino-phenyl)-4-{[(2/3/4-substituted-phenylcarbamoyl)-methyl]-amino}-butyramide and N-(2-amino-phenyl)-4-{[(2/3/4-substituted-phenylcarbamoyl)-methyl]-amino}benzamide were designed and synthesized as novel histone deacetylase inhibitors. The anticancer potential of the compounds were determined in-vitro using MTT assay against HCT-116 and U251 (glioma) cell lines and histone deacetylase inhibitory assay. The synthesized compounds were investigated for anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. The efforts were also made to ascertain structure-activity relationships among test compounds. The results of the present studying represents appraisal of γ-aminobutyric acid (GABA) and para-aminobenzoic acid (PABA) as linker moiety for development of newer benzamide based histone deacetylase inhibitor.