OBJECTIVE To prepare ferulic acid microemulsion-thermosensitive gel and evaluate its in vitro physicochemical properties, transdermal ability and skin retention.

METHODS Thermosensitive gel was prepared by using poloxamer 188 and poloxamer 407 as gel matrix based on ferulic acid microemulsion, then its appearance, microscopic morphology, particle size, pH value, viscosity, gel temperature, gelling time and stability were all evaluated. Using the dorsal skin of male rats as a permeation barrier, the Franz diffusion cell method was employed to investigate the skin permeability and skin retention of three different formulations and drug loads of ferulic acid.

RESULTS The formulation composition of ferulic acid microemulsion-thermosensitive gel was poloxamer 188∶poloxamer 407∶water∶ferulic acid pre-microemulsion=0.4∶5.0∶24.5∶1.5. This microemulsion-thermosensitive gel would present a colorless, clear and flowable liquid at room temperature, then transform into semisolid at skin temperature. At the same time, the gel exhibited spherical microemulsion droplets, its average particle size was (13.74±3.89)nm, polydispersion coefficient was (0.263±0.071), pH value was (6.05±0.21), viscosity was (179.76±15.34)mPa·s, gelation temperature was (31.91±0.14)℃, gelation time was less than 1 min, and it had good stability within 30 d. In suspension, microemulsion and microemulsion-thermosensitive gel, the penetration rate constant of ferulic acid was 4.560 2, 12.339 0, 7.255 4 μg·cm⁻²·h⁻¹, the cumulative penetration rate within 12 h was (39.10±3.54), (99.27±9.06), (71.94±6.58)μg·cm⁻², and the skin retention was (42.97±4.91), (47.07±7.45), (44.97±5.96)μg·cm⁻², respectively. In microemulsion-thermosensitive gel with low, medium and high drug loading, the penetration rate constant of ferulic acid was 1.024 9, 3.998 5, 7.255 4 μg·cm⁻²·h⁻¹, the cumulative penetration rate within 12 h was (14.03±1.07), (37.21±4.88), (71.94±6.58)μg·cm⁻², and the skin retention was (15.35±3.03), (32.04±6.47), (44.97±5.96)μg·cm⁻², separately.

CONCLUSION Ferulic acid microemulsion-thermosensitive gel has favorable temperature sensitivity, transdermal permeability and skin retention effect, which is expected to be a novel vehicle for the topical use of ferulic acid.