Bosentan loaded Nano structured lipid carriers: A novel formulation and evaluation of their In-vitro, Ex-vivo and In-vivo characteristic using 3² full factorial design.

This study carried out to improve bioavailability and reduce dose frequency of Bosentan, because of drug accumulation due to conventional therapy it cause serious liver toxicity. Bosentan loaded nanostructured lipid carriers (NLCs) prepared by using high-speed homogenization followed by an ultra-sonication. Optimization done by response surface methodology to identify the effect of solid to liquid lipid ratio (X1) and surfactant strength (X2) on the particle size (Y1) and drug loading (Y2). From the Preformulation study Precirol ATO 5, Transcutol HP and Poloxamer 188 selected as a solid lipid, liquid lipid and surfactant, respectively. Optimize formula having solid to liquid lipid ratio (85:15) %w/w and surfactant strength 1% w/v. Final formulation contained particle size 144.5±0.34 nm (n=3), surface charge -36.6 mv and 90.89±0.10 % (n=3) drug entrapment. Characterization performed using DSC, FTIR and TEM analysis. The Haemolytic study carried out to check blood compatibility. In-Vitro and Ex -Vivo drug release study shows 93.36% and 88.87 %, respectively after 24 hours. In-vivo Performance was conducted on wistar Albino rats. As per the result of in-vivo study pharmacokinetic parameters were quite different for Conventional formulation and NLCs. Bosentan NLCs absorb through the lymphatic system containing Peyer's patches. Optimize stable formulation gives the controlled release according to Fick's law. As uptake of Bosentan NLCs through Peyer's patches it may improve the bioavailability of the drug and reduce the liver toxicity. [ABSTRACT FROM AUTHOR]