Alpha-Asarone incorporated in mixed micelles suitable for intravenous administration: formulation, in-vivo distribution and anaphylaxis study

作者：Ren, Chunjuan^*; Gong, Tao; Sun, Xun; Zhang, Zhirong; Zhang, Yan

来源：Pharmazie, 2011, 66(11): 875-880.

DOI：10.1691/ph.2011.1035

• ACTIVE SYSTEMIC-ANAPHYLAXIS
• BILE-SALTS
• DRUG SOLUBILITY
• PHOSPHATIDYLCHOLINE
• STABILITY
• POLYSORBATE-80
• SENSITIZATION
• MEMBRANE
• CELLS
• DPPC

Alpha-Asarone is clinically used as a commercial intravenous formulation (CA-AREs). However, Polysorbate 80, a solubilizing agent contained in the formulation has been reported to be toxic. To enhance the aqueous solubility of ARE and to reduce the toxicity of CA-AREs caused by solubilizing agents, ARE loaded soybean phosphatidylcholine-deoxysodium cholate-mixed micelles (ARE-SPC-DC-MMs) were prepared and characterized in this study. Furthermore, pharmacokinetics and tissue distributions of ARE-SPC-DC-MMs and CA-AREs were also investigated. Additionally, the anaphylaxis of both of the two formulations was evaluated. The mean size of mixed micelles (ARE-SPC-DC-MMs) was 24.74 +/- 1.14 nm and the ARE solubility within the mixed micelles was approximately 30-fold greater than that of free drug in water. ARE-SPC-DC-MMs showed pharmacokinetic parameters similar to CA-AREs. AUC ((0 -> t)) (mg/L.min) of ARE-SPC-DC-MMs was lower in spleen than that of CA-AREs (p<0.05) while it was greater in the lung (p<0.05). There was no significant difference in other organs. These findings demonstrated that in comparison with CA-AREs, ARE-SPC-DC-MMs had similar properties in vivo, but led to higher accumulation of ARE in lungs. Meanwhile there was nearly no anaphylactic reaction caused by ARE-SPC-DC-MMs, but reactions could be observed in the CA-AREs group with significantly higher histamine release. In conclusion, ARE-SPC-DC-MMs could be an excellent substitute for commercially available CA-AREs for intravenous administration.

• 出版日期2011-11
• 单位四川大学