Eugenol- and Iodoform-Loaded Lipid Liquid Crystal Dressing for Alveolar Osteitis: Formulation, In Vitro Evaluation, and a Double-Blind Randomized Clinical Trial

This study aimed to formulate and clinically evaluate a novel lipid liquid crystal (LLC) dressing containing eugenol and iodoform, designed for sustained release, antimicrobial activity, and pain relief in alveolar osteitis (AO). Formulations with varying ratios of phosphatidylcholine (PC), sorbitan monooleate (SMO), glyceryl monooleate (GMO), and N-methyl-2-pyrrolidone (NMP) were prepared. The formulation which showed a good physicochemical stability and suitable viscosity was selected for further studies (F17, the optimized formulation). The optimized formulation was characterized for physicochemical properties and in vitro release. In a double-blind, randomized trial with 60 AO patients, the LLC-dressing was compared to Alvogyl® for pain, analgesic use, and dressing applications over seven days. The optimized formulation (F17) contained 35.25% PC, 35.25% SMO, 13.7% eugenol, and 15.8% iodoform, demonstrating an improved sustained drug release profile, appropriate viscosity, effective antibacterial activity, 100% encapsulation efficiency, and drug loading of 13.7% (eugenol) and 15.8% (iodoform). Visual Analog Scale (VAS) pain scores were comparable between LLC-dressing and Alvogyl® at all assessed time points, with no significant differences (0 h: 8.14 ± 1.40 vs. 7.96 ± 1.02; 7 days: 0.70 ± 0.66 vs. 0.78 ± 0.60; p > 0.05). Analgesic use (5.51 ± 3.06 vs. 6.13 ± 2.87, P = 0.401) and dressing applications (2.27 ± 1.12 vs. 2.57 ± 1.20, P = 0.345) showed similar efficiency. The optimized LLC-dressing (F17) exhibits favorable physicochemical and in vitro characteristics and may be considered a potential alternative to Alvogyl® for the management of AO.