Formulation and development of novel control release transdermal patches of carvedilol to improve bioavailability for the treatment of heart failure.

The main aim of this study is to optimize and evaluate transdermal patch of Carvedilol by the use of different polymer and different permeation enhancers which help to release drug in controlled action and thereby increase the bioavailability of the drug. Main objective was to avoid first pass metabolism of Carvedilol. Transdermal patches were developed by solvent evaporation method. The combination of Eudragit RS-100 as rate controlling polymer and Span 80 as a permeation enhancer was found to be ideal formulation (Formulation F7) with maximum drug release i.e. 100.29 ± 0.44 % within 12 h. Formulation F7 showed maximum bioavailability and showed maximum drop of BP at 6 h. From this study the conclusion was, transdermal patch of Carvedilol which contains Eudragit RS-100 polymer and Span 80 as penetration enhancer produced sustained and continued drug release.

[Protective effects of metformin on low-density lipoprotein-induced endothelial dysfunction in rats].

OBJECTIVE: To observe the protective effect of metformin on the endothelial function and the mechanisms in rats with low-density lipoprotein (LDL) injection. METHODS: A single dose (4 mg/kg) of natural LDL was injected through the sublingual vein of rats to induce vascular endothelial dysfunction. Blood samples were then collected from the rats to detect the concentrations of malondialdehyde (MDA) and nitric oxide (NO), activity of superoxide dismutase (SOD) and serum lipid levels. The thoracic aorta of rats was obtained to assay acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelium-independent relaxation. The effects of metformin pretreatment on the endothelial functions in the rats were investigated. RESULTS: A single-dose LDL significantly inhibited ACh-induced EDR without affecting SNP-induced endothelial-independent relaxation. The injection decreased serum NO and elevated serum MDA level, but had no effect on serum lipid level. Metformin markedly attenuated LDL-induced inhibition of EDR, serum MDA elevation, and serum NO reduction without affecting the serum lipid levels. CONCLUSION: Metformin provides protection against vascular endothelial dysfunction induced by LDL in rats, the mechanism of which is probably associated with protection of endothelium-dependent relaxation factor and inhibition of the oxidative stress.