目的 制备干扰素 α-2b （ IFNα-2b ）干粉吸入剂，并评价其体外性质以及大鼠体内的药动学性质。 方法 冷冻干燥并研磨后制备 IFNα-2b 干粉吸入剂，同时考察了 IFNα-2b 干粉吸入剂的形态、粒径、吸湿性、排空率及雾粒分布，并以细胞病变抑制法（ CPE 法）测定了干粉吸入剂中 IFNα-2b 的效价及活性保持率。此外，还以皮下注射 IFNα-2b 溶液为对照，考察了 IFNα-2b 干粉吸入剂在大鼠体内的药动学性质。 结果 IFNα-2b 干粉吸入剂形态为近圆形，粒径为 6.78 μm ，敲击密度为 0.35 g ·mL-1 ，排空率为 95.16% ，吸湿率为 5.80% ，雾粒分布实验中一级和二级瓶中的分布总量为 58.32 ％，干粉吸入剂中 IFNα-2b 的活性保持率为 99.58% ； IFNα-2b 干粉吸入剂在大鼠体内 <> c max 有所降低， <> t max 有所减小，相对生物利用度为 46.76% ； 结论 本实验所制备的 IFNα-2b 干粉吸入剂体外各项指标均符合要求， IFNα-2b 的活性损失小，而且体内生物利用度高。
Abstract
OBJECTIVE To prepare and characterize IFNα-2b dry powder inhalers (DPIs). METHODS IFNα-2b solution containing excipients was freeze-dried and grinded to obtain IFNα-2b DPIs. The appearance, particle size, hydroscopicity, emptying rate, tapped density, particle distribution and activity of IFNα-2b were investigated. The activity of IFNα-2b was determined by CPE. In addition, the pharmacokinetics of IFNα-2b DPIs in rats were also investigated with IFNα-2b subcutaneous injections as control. RESULTS The particles of IFNα-2b DPIs were almost round. The average diameter was 6.78 μm. The hydroscopicity at RH75% for 24 h was 5.80%. The emptying rate was 95.16%. The total amount of first and second distribution in particle distribution test was 58.23%. 99.58% IFNα-2b was active. cmax of IFNα-2b DPIs in rats was lower and tmax was shorter than those of IFNα-2b solution. The relative bioavailability for IFNα-2b DPIs in rats was 46.76%. CONCLUSIONS The activity of INFα-2b is maintained, and the bioavailability of IFNα-2b is high. All of the results suggest that IFNα-2b DPIs is helpful for the delivery of IFNα-2b into lung.
关键词
干扰素 α-2b /
干粉吸入剂 /
药动学
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Key words
IFNα-2b /
dry powder inhalers /
pharmacokinetic
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参考文献
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（ 收稿日期 ： 2009-06-11 ）
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