Preparation of Sinomenine Microemulsion by D-Optimal Mixture Design and Evaluation of Its Pharmacodynamics

  OBJECTIVE  To optimize the preparation process of sinomenine microemulsion and evaluate its pharmacodynamics.

  METHODS  HPLC method for sinomenine content determination was established, and sinomenine microemulsion prescription was initially screened by solubility test and pseudo-ternary phase diagram. D-optimal mixing experimental design method was used to optimize sinomenine microemulsion prescription with particle size and drug load as investigation indexes, and its particle size, drug load and stability were evaluated. Transdermal absorption was investigated by transdermal test in vitro, and the anti-inflammatory effect was evaluated by ear swelling test.

  RESULTS  With methanol:0.1% phosphoric acid (40∶60) as the mobile phase, the detection wavelength was 262 nm, and the method was suitable for the determination of sinomenine. The optimal formula of microemulsion was obtained as castor oil (7.0%), PEG40 hydrogenated castor oil/anhydrous ethanol (69.0%), the optimal Km value was 3∶1, and distilled water (24.0%). The average particle size of the microemulsion was 18.76 nm, the PDI was 0.072 and the drug loading was 5.225%. The cumulative permeability of 1.0% sinomenine microemulsion at 12 h was 1.223 4 μg·cm^-2, and the steady permeability rate was 0.0649 μg·cm^-2·h^-1, which was better than sinomenine solution. The inhibitory rate of sinomenine microemulsion was 65.07%, which was similar to dexamethasone.

  CONCLUSION  The preparation of sinomenine microemulsion has the advantages of stable process, high drug loading, good transdermal absorption and anti-inflammatory effect, which can provide reference for the development of sinomenine transdermal drug delivery preparation.