Prediction of in vivo drug performance using in vitro dissolution coupled with STELLA: a study with selected drug products

Prediction of the in vivo performance of the drug product from the in vitro studies is the major challenging job for the pharmaceutical industries. From the current regulatory perspective, biorelevant dissolution media should now be considered as quality control media in order to avoid the risk associated. Physiological based pharmacokinetic models (PBPK) coupled with biorelevant dissolution medium is widely used in simulation and prediction of the plasma drug concentration and in vivo drug performance. The present investigation deals with the evaluation of biorelevant dissolution media as well as in vivo drug performance by PBPK modelling using STELLA® simulation software. The PBPK model was developed using STELLA® using dissolution kinetics, solubility, standard gastrointestinal parameters and post-absorptive disposition parameters. The drug product selected for the present study includes Linezolid film-coated immediate-release tablets (Zyvox), Tacrolimus prolonged-release capsules (Advagraf), Valganciclovir tablets (Valcyte) and Mesalamine controlled-release capsules (Pentasa) each belonging to different biopharmaceutics classification system (BCS). The simulated plasma drug concentration was analyzed and pharmacokinetic parameters were calculated and compared with the reported values. The result from the present investigation indicates that STELLA® when coupled with biorelevant dissolution media can predict the in vivo performance of the drug product with prediction error less than 20% irrespective of the dosage form (immediate release versus modified release) and BCS Classification. Thus, STELLA® can be used for in vivo drug prediction which will be helpful in generic drug development.     

Solar cell array parameters

A generalized method of combining non identical parameters like series and shunt resistance dependent photocurrents under open circuit conditions (I_phoa) and the loaded conditions (I_pha) have been deduced. It is found that in the case of series array, only I_pha is dependent upon shunt resistance, while in the case of parallel array both are dependent upon shunt resistance.     

Chemopreventive Effect of Different Ratios of Fish Oil and Corn Oil in Experimental Colon Carcinogenesis

n-3 Polyunsaturated fatty acids (PUFA) have a chemopreventive effect while n-6 PUFA promote carcinogenesis. The effect of these essential fatty acids may be related to oxidative stress. Therefore, the study was designed to evaluate the effect of different ratios of fish oil (FO) and corn oil (CO) in the prevention of colon cancer. Male Wistar rats were divided into control, dimethylhydrazine dihydrochloride (DMH) treated, FO + CO (1:1) and FO + CO (2.5:1). All the groups, except the control received a weekly injection of DMH for 4 weeks. The animals were sacrificed either 48 h later (initiation phase) or kept for 16 weeks (post initiation phase). DMH treatment in the initiation phase animals showed mild to moderate inflammation, decreased ROS and TrxR activity, increased antioxidants, apoptosis and ACF multiplicity. The post initiation study showed severe inflammation with hyperplasia, increased ACF multiplicity and ROS levels, a decrease in antioxidants and apoptosis. The FO + CO (1:1) treated animals showed severe inflammation, a decrease in ROS, an increase in antioxidants and apoptosis in the initiation phase. FO + CO (1:1) in the post initiation phase and FO + CO (2.5:1) in the initiation showed mild inflammation, increased ROS, apoptosis and decreased antioxidants. There was a decrease in ACF multiplicity and ROS levels, increased antioxidants and apoptosis in the post initiation phase study. The present study suggests that FO has a dose- and time-dependent chemopreventive effect in colon cancer mediated through oxidative stress and apoptosis.     

Cryogenic Yb3+-Doped Solid-State Lasers

Cryogenically cooled solid-state lasers promise a revolution in power scalability while maintaining a good beam quality because of significant improvements in efficiency and thermo-optic properties. This is particularly true for Yb lasers because of their relatively low quantum defect and relatively broadband absorption even at cryogenic temperatures. Thermo-optic properties of host materials, including thermal conductivity, thermal expansion, and refractive index at low temperature, are reviewed and data presented for YAG (ceramic and single crystal), GGG, GdVO₄, and Y₂O₃. Spectroscopic properties of Yb:YAG and Yb:LiYF₄ (YLF) including absorption cross sections, emission cross sections, and fluorescence lifetimes at cryogenic temperatures are characterized. Recent experiments have pushed the power from an end-pumped cryogenically cooled Yb:YAG laser to 455-W continuous-wave output power from 640-W incident pump power at an of M² 1.4.