ABSTRACT
The solubility enhancement of poorly soluble compounds is an important task in pharmaceutical technology as it leads to better bioavailability and a more efficient application. Fused dispersions [FDs] of simvastatin [SIM] using PEO-PPO block copolymer were prepared which paved the way for the formation of an amorphous product with enhanced dissolution and bioavailability. The accumulative solubility of simvastatin [SIM] from PEO-PPO block copolymer [Lutrol NF 127 prill surfactant] was found to be superior to the drug alone which may be due to the increased oxyethylene content that played the major role in solubility enhancement. A 3[2] full factorial approach was used for optimization wherein the temperature to which the melt-drug mixture cooled [X[1]] and the drug-to-polymer ratio [X[2]] were selected as the independent variables and the time required for 90% drug dissolution [t[90%]] was selected as the dependent variable. A low level of X[1] and a high level of X[2] were suitable for obtaining higher dissolution of SIM from SIM FDs. On increasing melt to cool drug temperature, t[90%] increased thus improving dissolution rate of FD[2] batch with the maximum drug release [99.63%] in 120 min. The optimized FDs were characterized by saturation solubility study, drug content, in-vitro dissolution, fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, x-ray diffraction, [1]HNMR spectroscopy and pharmacodynamic evaluation. Capsules containing optimized FDs were prepared and compared with marketed brand [SIMVOTIN[registered]]. Finally, it can be concluded that the optimized FDs of SIM ameliorate the solubility and dissolution of drug with improved pharmacodynamic activity
ABSTRACT
Malaria parasites adapt to the oxidative stress during their erythrocytic stages with the help of vital thioredoxin redox system and glutathione redox system. Glutathione reductase and thioredoxin reductase are important enzymes of these redox systems that help parasites to maintain an adequate intracellular redox environment. In the present study, activities of glutathione reductase and thioredoxin reductase were investigated in normal and Plasmodium berghei-infected mice red blood cells and their fractions. Activities of glutathione reductase and thioredoxin reductase in P. berghei-infected host erythrocytes were found to be higher than those in normal host cells. These enzymes were mainly confined to the cytosolic part of cell-free P. berghei. Full characterization and understanding of these enzymes may promise advances in chemotherapy of malaria.