Optimization of Self-nanoemulsifying Drug Delivery Systems Containing Andrographolide: Design of Experiment Approach

Abstract

The objectives of this study were to optimize an andrographolide-loaded self-nanoemulsifying drug delivery system (SNEDDS) using a design of experiments (DoE) approach. Preformulation studies demonstrated that andrographolide exhibits low solubility and poor dissolution behavior, which may compromise its therapeutic efficacy. In parallel, molecular docking studies were conducted to explore the potential molecular mechanism of andrographolide in RCC. The results suggested that andrographolide is capable of forming favorable interactions within the active sites of VEGFR1 and VEGFR2, providing preliminary insight into its possible involvement in VEGF-related signaling pathways. A central composite design was employed to investigate the effects of formulation variables, including the oil fraction and the surfactant fraction in S_mix. Following optimization, the optimal formulation was obtained at an oil fraction of 0.10 and a surfactant fraction in S_mix of 0.61. The optimized SNEDDS exhibited a mean droplet size of 12.02 ± 0.25 nm, a polydispersity index of 0.113 ± 0.017, and good thermodynamic stability after heating-cooling cycles. The SNEDDS formulation significantly improved the dissolution behavior of andrographolide compared to the raw material, indicating its potential to overcome dissolution-limited absorption. Overall, this study demonstrates that DoE-guided optimization of an andrographolide-loaded SNEDDS, supported by preformulation insights, represents a rational and effective strategy to enhance drug dissolution and improve its pharmaceutical performance.