D-Optimal Mixture Design Optimization of Curcumin SNEDDS and Its Development into an Antioxidant Gel

Abstract

Curcumin is a natural polyphenol with high antioxidant capacity, but its topical use is restricted by poor aqueous solubility, low stability and limited skin permeability. This study developed a curcumin self-nanoemulsifying drug delivery system (SNEDDS), optimised its composition with a D-optimal mixture design, and incorporated the optimum system into a hydrogel. Isopropyl myristate (IPM, 10–20%), Cremophor RH 40 (40–70%) and Transcutol P (10–40%) served as the oil, surfactant and co-surfactant. Sixteen design runs were characterised for droplet size, emulsification time, transmittance, drug loading, polydispersity index and zeta potential; models were fitted in Design-Expert 13 and the optimum composition was selected using the desirability function. All six response models were significant (p<0.05) with a non-significant lack of fit (p>0.05). The optimum composition was IPM 19.91%, Cremophor RH 40 70.00% and Transcutol P 10.08% (desirability 0.777), giving a droplet size of 44.25 nm, an emulsification time of 32.64 s, a transmittance of 93.20%, a drug loading of 22.84 mg/mL and a zeta potential of −12.66 mV, with no significant difference from the predicted values (p>0.05). The resulting gel was homogeneous, with pH 5.14±0.02, viscosity 26,330±1.54 cP, adhesion 5.95±0.47 s and spreadability 5.66±0.03 cm, and remained stable over six freeze–thaw cycles. DPPH assay gave an IC₅₀ of 8.73±0.004 µg/mL (AAI 4.52) for the SNEDDS gel versus 12.62±0.033 µg/mL (AAI 3.13) for the conventional gel. Franz diffusion showed a 49.1% higher flux and 79.3% higher cumulative diffusion at 120 min for the SNEDDS gel.