Posted by admin on Oct 1, 2014 in |
Thromboembolic disorders are the leading cause of human mortality. Therefore, development of effective anticoagulant therapy is critical. Factor XIIIA (FXIIIA) protein is a crucial factor in the blood coagulation cascade, and hence, it is a vital target for the evolution of new antithrombotic agents. Structure-function studies of clotting factor active sites, clot formation, and thrombus structure have gained prominence in the efforts to develop novel anticoagulants. Factor XIIIA was homology modeled with the human transglutaminase-2 crystal structure as a base template for BLAST analysis. Docking and comparative binding site analysis revealed active site residue conservation and inhibitor-protein interactions. Nineteen small molecules possessing suspected anticoagulant properties were successfully docked into the FXIIIA active site following the best CoMFA and CoMSIA prediction values. Dabigatran etexilate was anticipated to be the best FXIIIA inhibitor among the nineteen anticoagulants with the highest binding affinity for the FXIIIA protein, and the highest FlexX docks score of -29.8 KJ/mol. Structural properties of FXIIIA inhibitors with increased antithrombotic activity were predicted by this docking...
Read More
Posted by admin on Oct 1, 2014 in |
The present study was aimed to improve the water solubility and bioavailability of telmisartan by solid dispersion technique. Telmisartan is 4′-[(1,4′-dimethyl-2′-propyl[2,6′-bi-1H-benzimidazol]-1 ‘- yl) methyl]- [1, 1’-biphenyl]- 2- carboxylic acid. Telmisartan is practically insoluble in water. Telmisartan is an angiotensin II receptor antagonist (ARB), used in the management of hypertension. Solid dispersions of telmisartan were prepared by using polyethylene glycol 4000 and mannitol as hydrophilic carriers in different weight ratios by a solvent evaporation method. The drug and the solid dispersions were characterized by saturation solubility studies, in-vitro dissolution study, Fourier-transform infrared spectroscopy, differential scanning calorimetry, drug content estimation, and stability study. Based on physical characters and drug release pattern, formulation F2 (1 g drug, 4 g PEG 4000 and 1 g mannitol) exhibited the best results. The carriers, polyethylene glycol 4000 and mannitol, were found to be effective in increasing the aqueous solubility and dissolution rate of telmisartan in solid dispersions when compared to the pure...
Read More
Posted by admin on Oct 1, 2014 in |
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor, a promising anticancer agent for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), especially in EGFR mutated patients. It acts by interfering with the proliferation and survival of cancer cells and other host-dependent process promoting cancer cell growth by blocking signal transduction pathways. The major advantage of Gefitinib over standard chemotherapy is that it selectively inhibits cellular pathways involved in tumor survival with minimal effect on normal cells. Gefitinib was the first agent to be tested in clinical trials among tyrosine kinase inhibitors class of anticancer drugs. Gefitinib is a very slightly soluble novel anticancer drug whose solubility and dissolution can be improved by its complexation with cyclodextrins. Gefitinib is a generally well-tolerated treatment, with skin rash and diarrhea being the most common treatment adverse effects. Gefitinib has the potential of stimulating cell immunity against malignant cells. Binding of Gefitinib to human plasma protein is extensive. This article reviews the safety and efficacy of Gefitinib...
Read More
Posted by admin on Oct 1, 2014 in |
Chronotherapy involves the release of drug to the systemic circulation based on the circadian rhythm associated with the pathophysiology of a disease. Candesartan Cilexetil, an anti-hypertensive drug, is formulated to contribute to the chronotherapy of hypertension. Solubility study of the drug (BCS Class II) in various media indicated maximum solubility in pH 6.8 sodium phosphate buffer containing 1% SLS. Solid dispersion of Candesartan Cilexetil with PVP K30 was prepared by melt dispersion. Core tablet containing solid dispersion equivalent to 16mg Candesartan Cilexetil was prepared by direct compression. The % dissolution efficiency (DE60) of the pure drug was 31.05% and increased for the solid dispersion to 56%. Compression coating was applied to this core tablet by direct compression using release rate retardants HPMC K15M and Eudragit S100 in various proportions to give timed-release. In-vitro drug release test carried out in 0.1 N HCl for the first 2 h and pH 6.8 buffer containing 1% SLS for next 8 hrs showed formulation F4 containing 75 % of HPMC K15M and 25%...
Read More
Posted by admin on Oct 1, 2014 in |
Cancer is a very complex genetic disorder that is mainly caused by carcinogens. Carcinogens can be present in the air, water, food, chemicals, and sunlight that are exposed to the people. In the case of leukemia, the body produces large numbers of abnormal white blood cells. In the study of blood cancer that is leukemia, blood disorders through visual inspection of microscopic images of blood cells is an important diagnostic tool. From the identification of blood disorders, it can lead to the classification of certain diseases related to blood. Doxorubicin drug most useful for cancer treatment such as Breast cancer, ovarian cancer, Lung cancer, Neuroblastoma cancer, Leukemia, etc. In breast cancer, the efficacy of drug treatment will thus depend on the histology of the tumor tissue. In ovarian cancer, the doxorubicin metabolites accumulated in the ascites and cleared more slowly from the peritoneal compartment than from the serum. Accumulation in the peritoneal cavity with prolonged half-life should be considered when administering medication in patients with ascites. In lungs cancer,...
Read More
