College of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, PR China.
Shineway Pharmaceutical Co. Ltd., 682 Yingbin Road, Sanhe, Hebei 065201, PR China.
Eur J Pharm Sci. 2017 Jun 15;104:13-22. doi: 10.1016/j.ejps.2017.03.017. Epub 2017 Mar 14.
Andrographolide (Andro) is an excellent anti-inflammatory bicyclic diterpene γ-lactone. However, the poor solubility limits its application as injection for the treatment of acute inflammation. To meet the clinical needs for emergency, the Andro nanosuspensions injection was first prepared by the wet milling technique. The Andro nanosuspensions were composed of 3% Andro, 5% poloxamer 188 as the non-ionic stabilizer, 0.05% sodium deoxycholate or 0.1% sodium tauroursodeoxy cholate as the ionic stabilizer, and prepared by 350rpm speed and 12cycles of grinding with 0.4mm zirconium oxide pearls. The nanosuspensions showed hexagonal morphology with particle size of 300nm, and no change in crystalline state of Andro after milling. The nanosuspensions had a significant increase in saturation solubility, and could completely release within 0.25h (bulk Andro within 24h). The lyophilized product of Andro nanosuspensions with mannitol (5%) as lyoprotectant had good physical and chemical stability during the 6-month storage period. The pharmacokinetic and tissue distribution results showed that it was rapidly eliminated from the blood and largely distributed in the liver. Overall, the Andro nanosuspensions may be used as a potential formulation for the treatment of liver infections owing to its passive liver targeting function.
穿心莲内酯（Andro）是一种出色的抗炎双环二萜γ-内酯。然而，其较差的溶解度限制了其作为注射剂用于治疗急性炎症的应用。为满足临床对急症的需求，首次采用湿磨技术制备了穿心莲内酯纳米混悬注射液。穿心莲内酯纳米混悬剂由 3%的穿心莲内酯、5%的泊洛沙姆 188 作为非离子稳定剂、0.05%脱氧胆酸钠或 0.1%牛磺胆酸钠作为离子稳定剂组成，采用 350rpm 转速和 0.4mm 氧化锆珠 12 次研磨制备。纳米混悬剂呈六方形态，粒径为 300nm，研磨后穿心莲内酯的晶体状态没有变化。纳米混悬剂的饱和溶解度显著增加，可在 0.25h 内完全释放（普通穿心莲内酯 24h 内）。以甘露醇（5%）作为冻干保护剂的穿心莲内酯纳米混悬剂冻干产品在 6 个月的储存期内具有良好的物理化学稳定性。药代动力学和组织分布结果表明，它在血液中迅速消除，并主要分布在肝脏中。总的来说，由于其被动肝靶向功能，穿心莲内酯纳米混悬剂可能被用作治疗肝脏感染的潜在制剂。
