Formulation, Optimization, and In vitro Characterization of Cilnidipine-loaded Self-emulsifying Drug Delivery System

Abstract

The goal of this research was to formulate and optimize a cost-effective self-emulsifying drug delivery system (SEDDS) of cilnidipine to increase its dissolution rate. Cilni-dipine is a BCS class II active pharmaceutical ingredient, which limits its use. Cilnidipine's solubility in various oils, surfactants, and cosurfactants, has been investigat-ed. To determine if there is any interaction between cilnidipine and certain excipients, drug compat-ibility tests were carried out. Based on phase solubility and compatibility studies, two combinations (Canola oil, Tween 80, and PEG 300; Peanut oil, Cremophor EL, and PEG 200) were prepared to create ternary phase diagrams for selecting the best combination with higher microemulsion region and to identify the range of concentration of excipients. Cilnidipine-loaded-SEDDS formulation was prepared by incorporating Canola oil, Tween 80, and PEG 300. For achieving the best formula-tion, D-optimal mixture design was used. The optimized SEDDS formulation was evaluated for globule size, zeta potential, drug release, drug content, self-emulsification time, and stability stud-ies. The zeta potential (Y1) and globule size (Y2) of the optimized SEDDS formulation were found to be -36mV and 124.3nm, respectively. The optimized SEDDS formulation showed more than 98% drug release within 15 min in 10% ethanolic 0.1N HCl media, which was significantly higher than that of the pure drug (7.5%) and marketed tablet (~21%). The optimized formulation's self-emulsification time, drug content, and cloud point were 55s, 99.97 ± 1.57 %, and 75.6℃, re-spectively. After stability studies, there was no evidence of phase separation, colour change, and change in globule size. A significant improvement in in vitro drug release was observed from cilnidipine-loaded-SEDDS.