The reverse dialysis bag method for the assessment of in vitro drug release from parenteral nanoemulsions: A case study of risperidone

The present study describes the release pattern of risperidone, a poorly water-soluble psychopharmacological drug, from two parenteral nanoemulsions containing the mixture of medium-chain triglycerides and soybean oil as an oil phase, sodium oleate solution as an aqueous phase and lecithin alone or in combination with polysorbate 80 as emulsifiers/stabilizers. The nanoemulsions were prepared by hot high-pressure homogenization, and evaluated regarding physicochemical properties - a droplet size, polydispersity index, zeta potential, and viscosity, as well as biopharmaceutical performances - in vitro drug release by employing a reverse dialysis bag technique. Physicochemical characterization revealed a favorable mean droplet size (160-210 nm), narrow size distribution (<0.15), high surface charge (around -50 mV to -60 mV) and low apparent viscosity (4-6 mPa.s) of developed nanoemulsions, thus proving their suitability for parenteral administration of poorly water-soluble actives. The in vitro drug release study showed biphasic release profiles of risperidone, with significant differences between two investigated nanoemulsion formulations (differing only in the presence of polysorbate 80), indicating the influence of nanoemulsion matrix on drug release kinetics. However, the release of risperidone from investigated nanoemulsions was relatively rapid (more than 50% released within the first 5 min), suggesting their promising application in emergency situations. Furthermore, above 95% of the drug was released from both tested nanoemulsions within 180 min, while the kinetic release process could be described by Korsmeyer-Peppas model and supposed to be diffusion-controlled.Overall, it can be concluded that the reverse dialysis bag technique was the appropriate and enough discriminatory method to evaluate the in vitro release of risperidone from presented nanoemulsion systems.