Development and evaluation of madecassoside-loaded microemulsion for enhanced topical drug delivery

Madecassoside, a major triterpenoid glycoside from Centella asiatica, has potential value for dermatological applications; however, its poor stratum corneum permeability is due to high hydrophilicity and large molecular size. This work focused on designing a microemulsion carrier to enhance the topical delivery of madecassoside. Formulation regions were first screened using pseudo-ternary phase diagrams, followed by preparation of madecassoside-loaded systems with different oil phases, surfactant HLB values, cosurfactant compositions, and drug loadings. The resulting formulations were characterized for droplet size, PDI, viscosity, rat-skin permeation, skin retention, CAM irritation response, and physical stability. All prepared systems were clear and homogeneous, with droplet sizes between 28.00 ± 0.44 and 60.10 ± 0.61 nm and PDI values not exceeding 0.27 ± 0.02. Further optimization identified M10, containing IPM, Brij 30/Brij 35, Transcutol HP, and 2% madecassoside, as the most suitable formulation. M10 produced a high 24 h cumulative permeation amount of 406.28 ± 180.73 μg/cm², corresponding to an approximately 43.2-fold increase compared with the 2% madecassoside control solution (9.41 ± 2.08 μg/cm²). In the HET-CAM assay, M10 showed an irritation score lower than the 1% SLS reference group. The formulation also remained clear after centrifugation, freeze-thaw cycling, and 30 days of storage, with no marked changes in droplet size, PDI, or viscosity. These results suggest that microemulsions are a promising strategy for enhancing topical madecassoside delivery.