Development and in vitro evaluation of self-emulsifying drug delivery systems liquisolid lozenges of ibuprofen via design of experiments for solubility enhancement and oral epithelial cell permeation

Ibuprofen lozenges were developed by converting liquid self-emulsifying drug delivery systems (L-SEDDS) into liquisolid compacts (LSCs) to enhance aqueous solubility, support local anti-inflammatory action in the oral and throat regions, and reduce gastrointestinal irritation. The solubility of ibuprofen in oils and nonionic surfactants was evaluated. Tween 60 showed the highest solubility (285.53 ± 19.31 mg/g), whereas Imwitor® 742 (135.12 ± 0.21 mg/g) provided a suitable oil phase. L-SEDDS composed of ibuprofen, Tween 60, and Imwitor® 742 (9:1, w/w) formed nanoemulsions in simulated salivary fluid (SSF) with droplet sizes of approximately 200 nm. The L-SEDDS was loaded onto polyvinylpyrrolidone, magnesium aluminosilicate, sucrose, or F-Melt® C (FMC) to obtain LSC lozenges. A three-factor Box–Behnken design was employed to investigate the effects of L-SEDDS level, PVP content, and diluent type on tablet hardness and mean dissolution time (MDT). Suitable sucrose-LSC (Run7) and FMC-LSC (Run13) formulations showed rapid dissolution in SSF, with MDT values of 6.59 ± 0.15 and 5.91 ± 0.13 min, respectively, compared with 45.34 ± 1.11 min for ibuprofen powder. In a KON cell monolayer model, L-SEDDS and FMC-LSC (Run13) increased the apparent permeability coefficient of ibuprofen by approximately 3.6- and 3.5-fold, respectively, compared with ibuprofen powder. Both formulations maintained ibuprofen content, droplet size, dissolution behavior, and mechanical strength after 6 months of storage under both ambient and accelerated conditions. These results indicate that L-SEDDS-based LSC lozenges, particularly the FMC formulation, provide a stable dosage form that improves dissolution and mucosal permeation of poorly water-soluble ibuprofen.