A full factorial design in the formulation of diazepam parenteral nanoemulsions: Physicochemical characterization and stability evaluation

Abstract

Using the experimental design methodology, we have developed and characterized nanoemulsions for a parenteral delivery using diazepam as a model drug. The formulations containing 20 or 30% (w/w) of medium chain triglycerides or the mixture of medium chain triglycerides and soybean oil as the oil phase, soybean lecithin and polysorbate 80 as emulsifiers, and a phosphate buffer solution as the aqueous phase were prepared by cold high pressure homogenization. The obtained nanoemulsions were evaluated in terms of droplet size, size distribution, surface charge, drug-vehicle interactions and physical stability. To evaluate the effects of the oil phase type, oil content and drug presence, as well as their interactions on critical quality attributes of nanoemulsions, a three-factor two-level full factorial design was applied. After the preparation, all nanoemulsions revealed small spherical droplets in the range 170-210 nm, with the narrow droplet size distribution (< 0.15) and the surface charge about -60 mV. The experimental design results indicated that not only factors alone (oil type, oil content, presence of drug), but their interactions also had a significant effect on the nanoemulsion droplet size, polydispersity index, and zeta potential. During two months of storage at 25°C, all nanoemulsions formulated with the medium chain triglycerides-soybean oil mixture (4:1, w/w) remained physically stable, without considerable changes in monitored parameters. Physicochemical characteristics and stability of these nanoemulsions demonstrated their suitability for parenteral drug delivery.