Formulation and In-Vitro Evaluation of a Nanoemulsion-Based System for Transdermal Drug Delivery

Many therapeutic agents have poor aqueous solubility, fast liver metabolism and low bioavailability, which are long-standing challenges for effective oral drug delivery. Transdermal delivery is a promising alternative due to the advantages of avoiding first pass metabolism and enhancing permeation of the drug across the stratum corneum by nanoemulsion based system. In this investigation, a novel nanoemulsion-based transdermal delivery system to deliver benidipine hydrochloride as a model drug was developed and evaluated. Pseudo-ternary phase diagrams were used to determine the best concentration of each component with isopropyl myristate as oil phase, Tween 80 and 20 as surfactant and propylene glycol and glycerol as cosurfactants. The influence of oil phase content and the composition of cosurfactants on droplet size, polydispersity index, zeta potential and drug loading were thoroughly studied. Physicochemical characterization included dynamic light scattering, thermodynamic stability studies by centrifugation and heating-cooling methods and in-vitro drug diffusion studies by dialysis membrane method. Morphology was assessed by transmission electron microscopy (TEM) and the long-term stability was evaluated after 6 months at ambient temperature. The optimized formulation showed average droplet size in the range of 48.3–82.4 nm and PDI value between 0.26 and 0.29 which indicated the homogeneous size distribution appropriate for transdermal penetration. The content of the drug was well maintained at the level of 99.3 to 99.6% throughout the study period. The nanoemulsion system was found to be able to retain the solubility of the drug in physiological pH and was found to possess sustained in-vitro release characteristics. The results indicate that the nanoemulsion based transdermal systems are promising delivery systems for poorly soluble pharmaceutical compounds.