Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol

ABSTRACT

In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 3² Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as C_max, T_max, Ke, Ka, V_d and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183 ± 2.43 nm with an entrapment efficiency of 81.4 ± 0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in C_max (two fold, p < 0.001) and AUC (four folds, p < 0.001) of carvedilol when compared to carvedilol suspension. Car-NS were found to be stable for a period of 3 months. Thus, a stable, floating, multiparticulate GMO/Eudragit E100 nanostructures having ability to release the drug in sustained manner with enhanced oral bioavailability can prove to be a promising carrier system for poorly water soluble drugs.

Keywords:

• Carvedilol
• Eudragit
• glyceryl monooleate
• oral bioavailability
• sustained drug release