Nanovesicular systems loaded with a recently approved second generation type-5 phospodiesterase inhibitor (avanafil): I. Plackett-Burman screening and characterization

The aim of this work was to study the effect of different processing and formulation factors on the preparation of nanoethosomes and nanoglycerosomes loaded with the recently approved second generation type-5 phospodiesterase inhibitor (avanafil). Different formulations were proposed utilizing the Plackett-Burman screening design. Phospholipid-to-drug ratio, edge activator type, edge activator concentration, hydration medium temperature, hydration medium pH and sonication time were investigated to study their effect on particle size, zeta potential, drug entrapment efficiency, and diffusion steady-state flux. The results revealed that both the phospholipid- to-drug ratio and sonication time had a pronounced effect on particle size, while the phospholipid-todrug ratio and hydration medium pH, showed a significant effect on drug entrapment efficiency, while edge activator concentration and sonication time showed a significant effect on diffusion steady-state flux. The optimized nanoethosomal formula comprised a 135.6 nm particle size, 65.2% entrapment efficiency, 29.5 mV zeta potential, and 8.2 mu g/cm(2). h steady-state flux. The ex-vivo permeation showed enhancement in permeability by more than five-fold corresponding to drug suspension. Significant variables could be further optimized to produce smaller particle size vesicles that could further increase the extent of drug permeation.