OBJECTIVE To screen the optimal formulations of luteolin solid dispersion(LU-SD) and luteolin self-microemulsion(LU-SME), and evaluate the in vivo pharmacokinetics(PK) and bioavailability of the two preparations.

METHODS LU-SD was prepared by spray drying method. The appropriate carrier and ratio were selected according to the solubility and dissolution, and the crystal stability was characterized by X-ray powder diffraction. Different oil phases, emulsifiers, co-emulsifiers and their ratios were selected to prepare LU-SME. The optimal formulation was screened based on dispersion/storage stability, solubility and dissolution as evaluation indices. LU injection, LU suspension, LU-SD and LU-SME were administered to rats via tail vein injection and oral gavage, and the in vivo PK and bioavailability of different formulations were compared.

RESULTS LU-SD prepared with the formulation of 25% LU and 75% PVP VA 64 exhibited approximately a 60-fold improvement in solubility compared with pure LU. Its cumulative dissolution reached 94.3% at 120 min, and it possessed favorable crystalline stability within 120 min in fasted-state simulated gastric fluid. The optimized LU-SME was fabricated using 30% phosphatidylcholine as the oil phase, 30% caprylocaproyl polyoxyl-8 glycerides as the surfactant, and 40% polyoxyl castor oil as the cosurfactant. This formulation achieved around a 68-fold increase in solubility relative to pure LU, with the maximum dissolution up to 95.2% within 15 min, accompanied by satisfactory dispersion and storage stability. In vivo PK studies demonstrated that LU-SME afforded higher oral bioavailability than LU-SD, and LU-SME showed a shorter time to peak concentration than LU-SD.

CONCLUSION Both LU-SD and LU-SME can significantly improve the solubility and dissolution of LU. Based on the results of this study, LU-SME has a greater advantage in improving bioavailability than LU-SD.