Abstract: Objectives: To investigate optimal conditions for inclusion complex formation between sinomenine and cylcodextrins and determine the inclusion constants and release in vitro of inclusion complexes prepared with different cyclodextrins. Methods: One-factor-at-a-time and orthogonal array design methods were employed for the optimization of inclusion complex formation conditions. The inclusion constants of sinomenine complexes with β-cylcodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and γ-cyclodextrin (γ-CD) formed under optimal conditions were determined by the phase solubility method. Moreover, their release in vitro was tested. Results: The optimal conditions for forming sinomenine-cylcodextrins inclusion complexes were 1:1 of sinomenine-to-cylcodextrin molar ratio, 50 ℃ of temperature, and 3 h of reaction duration at pH 7. The inclusion constants of sinomenine-β-CD, sinomenine-HP-β-CD and sinomenine-γ-CD formed under these conditions were calculated as 501.1, 150.0, 600.3 L/mol, respectively. Conclusion: sinomenine and cylcodextrins can form stable inclusion complexes at a molar ratio of 1:1. Various inclusion complexes show remarkable sustained release effect on sinomenine.

Key words: sinomenine, cylcodextrins, inclusion constant, orthogonal array design, process optimization