Effects of carbohydrate polymers in self-microemulsified tablets on the bioavailability of atorvastatin: In vitro-in vivo study.

AIMS: The concentrations of crospovidone (CP), maltodextrin and microcrystalline cellulose (MCC) have been optimized in the development of self-microemulsified tablets (SMET) to improve the oral bioavailability of an anti-hyperlipidemic drug, atorvastatin, and the in-vivo pharmacokinetic parameters of the optimized SMET were compared with those of a commercial tablet in rabbits. MAIN METHODS: Self microemulsified liquids (SELS) were prepared with oleic acid, Span 40 and Tween 80. SELS were converted into SMET by adsorption, followed by compression using factors such as CP, maltodextrin and MCC, which were optimized through a 2(3)-factorial design considering responses such as the disintegration time and, the times for 50% and 80% of the drug to be released. KEY FINDINGS: The results indicated that CP and MCC were inversely related to the responses, while maltodextrin was directly related to the responses. The droplet size of the disintegrated SMET oil globules was within 2.73 to 4.77 µm. The Cmax and AUC0-∞ of the optimized SMET were found to be 32.5% and 38.8% higher, respectively, than those of the commercial tablet. SIGNIFICANCE: The present results indicate that the bioavailability of the SMET of atorvastatin is better than the commercial formulation.

The neuronal apoptotic death in global cerebral ischemia in gerbil: important role for sodium channel modulator.

Global ischemia was induced in gerbil by bilateral occlusion of the common carotid arteries for 5 min. Sodium ionophore monensin or sodium channel blocker tetrodotoxin (TTX) was administered at doses of 10 micorg/kg, i.p., 30 min before ischemia induction; the dose was repeated after 22 hr. Subsequently, brain infarct occurred, determined at 24 hr after occlusion. Large, well-demarcated infarcts were observed in both hemispheres, an important observation because it critically influences the interpretation of the data. Because nitric oxide (NO) production is thought to be related to ischemic neuronal damage, we examined increases in Ca(2+) influx, which lead to the activation of nitric oxide synthase (NOS). Then we evaluated the contributions of neuronal NOS, endothelial NOS, and inducible NOS to NO production in brain cryosections. The cytosolic release of apoptogenic molecules like cytochrome c and p53 were confirmed after 24 hr of reflow. TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) labeling detected the apoptotic cells, which were confirmed in neuron-rich cell populations. After 24 hr, all the ischemic changes were amplified by monensin and significantly attenuated by TTX treatment. Additionally, the nesting behavior and histological outcomes were examined after 7 day of reflow. The neuronal damage in the hippocampal area and significant decrease in nesting scores were observed with monensin treatment and reduced by TTX pretreatment after day 7 of reflow. To our knowledge, this report is the first to highlight the involvement of the voltage-sensitive Na(+) channel in possibly regulating in part NO system and apoptosis in a cytochrome c-dependent manner in global ischemia in the gerbil, and thus warrants further investigation.