Systematic development of DoE optimized SNEDDS of sirolimus with enhanced intestinal absorption

Abstract

This study aimed on defining the role of formulation components and computational optimization of sirolimus self-nanoemulsifying drug delivery system (SNEDDS). Applicability of components in enhancing intestinal absorption was investigated. Box-Behnken design was run to evaluate the effect of component amounts on transmittance, droplet size, polydispersity index, refractive index, and zeta potential of nanoemulsions. Surface properties of vehicles, SNEDDSs and nanoemulsions were investigated. Dissolution profiles and intestinal permeabilities of Miglyol 812 or Capryol PGMC-based optimized formulations were determined. Nanoemulsions containing more Cremophor RH 40, exhibited the lowest surface tension. Droplet size of optimized Capryol-based SNEDDS was 4538 nm. Applying Capryol PGMC resulted in the highest dissolution and permeability enhancement. Intestinal permeability of Capryol and Migliol-based formulations were 4.15 and 2.73 times higher than that of sirolimus solution. Statistical design allowed us to screen the effect of each component in formation of desired sirolimus nanoemulsions. Capryol-based SNEDDS could promisingly enhance the intestinal permeability of sirolimus.