Objective: Glaucocalyxin A (GLA) suffers from low oral bioavailability and rapid in vivo metabolism. Therefore, the purpose of this study was to develop a new formulation to enhance the oral bioavailability simultaneously sustained release of GLA.

Material and methods: GLA-phospholipid complex was firstly formulated by solvent-evaporation method to improve the solubility of GLA. Differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, and solubility study were used to characterize the GLA-phospholipid complex. And then, the optimized GLA-phospholipid complex was selected to prepare GLA-phospholipid complex sustained release pellets by extrusion-spheronization and fluidized bed coating technology. The prepared pellets were studied by in vitro drug release study and administered to beagle dogs to evaluate the oral bioavailability of GLA-phospholipid complex and GLA-phospholipid complex sustained release pellets.

Results: The results illustrated that GLA in GLA-phospholipid complex was either molecularly dispersed or in an amorphous form with 13.8-fold water solubility than the free GLA. The pharmacokinetic studies in beagle dogs demonstrated that GLA-phospholipid complex and GLAphospholipid complex sustained-release pellets showed 2.19-fold and 2.07-fold improvement than the free GLA by oral dosage, respectively. Further, steady plasma concentration, and prolonger T_max were simultaneously obtained from GLA-phospholipid complex sustained release pellet.

Conclusion: These outcomes suggested that the combination of phospholipid complex and sustained release pellets could enhance the oral bioavailability and prolong the action time in vivo which provided a promising delivery system for GLA.