Enhanced Oral Bioavailability of Carvedilol by Supersaturable Self Emulsifying Drug Delivery System

This study focused on the effect of formulation design on physico-chemical properties of self-emulsifying system, drug release, intestinal permeability and bioavailability upon oral delivery. A series of studies were conducted to optimize the suitable type and level of formulation additives which showed a positive impact on drug bioavailability. The optimized self-emulsifying system mainly consisted of mixture of Oleic acid and Labrafil M2125 as an oil-phase, Cremophor RH40 as a surfactant, Polyethylene glycol (PEG) 400 as a co-surfactant, HPMC E5 as a super-saturation promoter. Formulations were characterized for droplet size, polydispersity index, zeta potential, drug release studies in simulated and biorelevant dissolution media. Further, intestinal permeability and bioavailability studies were conducted in male Wistar rats. The optimized formulation quickly dispersed in aqueous phase and formed a clear emulsion having size of 234 nm. Dissolution studies clearly showed a distinct drug release pattern in both the compendial and biorelevant dissolution media. The role of super saturation promoter was observed in in vitro, ex vivo and in vivo studies. The results from in vivo studies depicted that, there was 2.23 folds increase in permeability and 3.2 folds increase in bioavailability in comparison with control.