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Alpha-Asarone incorporated in mixed micelles suitable for intravenous administration: formulation, in-vivo
Chunjuan Ren1, Tao Gong, Xun Sun
1Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, P. R. China.
Abstract:
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 x 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.
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