Protein deposition from dry powder inhalers: Fine particle multiplets as performance modifiers
Protein deposition from dry powder inhalers: Fine particle multiplets as performance modifiers
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DOI：
10.1023/a:1011977826711
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发表时间：
1998-04-01
影响因子：
3.7
通讯作者：
Staniforth, JN
中科院分区：
文献类型：
--
作者：
Lucas, P;Anderson, K;Staniforth, JN
目的.评估基于载体的干粉气雾剂用于蛋白质的吸入递送的用途，并检查细颗粒赋形剂作为潜在的制剂性能改进剂的效果。采用喷雾干燥法将牛血清白蛋白（BSA）与麦芽糊精共处理，制备模型蛋白颗粒。通过翻滚混合蛋白质粉末与α-乳糖一水合物（63-90 μ m）或含有2.5 - 10%w/w细颗粒乳糖（FPL）或微粉化聚乙二醇6000的改性乳糖来制备气雾剂制剂。粉末共混物的特征在于粒度分布，形态和粉末流动。使用双级撞击采样器以60 l min（-1）的工作速率研究了Dahaler（R）和Rotahaler（R）装置中的制剂性能。通过添加FPL和微粉化PEG 6000，使用BSA-麦芽糖糊精和乳糖（63-90 μ m）制备的二元有序混合物的吸入性能得到改善。对于加入5%w/w FPL，使用Escherhaler（R）的蛋白质细颗粒部分（0.5-6.4 μ m）从31.7 +/-2.4%增加到47.4 +/-2.2%。包含FPL和微粉化PEG 6000改变了吸入粉末的整体性质，并降低了粉末流量，但不影响装置排空。出乎意料的是，发现性能的改善与将FPL添加到三元粉末制剂中的顺序无关。SEM研究表明，这可能是混合过程中蛋白质颗粒在粗载体乳糖组分和添加的FPL之间重新分布的结果。细颗粒赋形剂可用于改善基于载体的蛋白质干粉气雾剂的性能。从机理上讲，提出性能的增强是由于蛋白质颗粒从粗载体颗粒重新分布到三元混合物中的细颗粒组分。
Purpose. To evaluate the use of carrier-based dry powder aerosols for inhalation delivery of proteins and examine the effect of fine particle excipients as potential formulation performance modifiers.Methods. Bovine serum albumin (BSA) was co-processed with maltodextrin by spray-drying to produce model protein particles. Aerosol formulations were prepared by tumble mixing protein powders with alpha-lactose monohydrate (63-90 mu m) or modified lactoses containing between 2.5 and 10% w/w fine particle lactose (FPL) or micronised polyethylene glycol 6000. Powder blends were characterised in terms of particle size distribution, morphology and powder flow. Formulation performance in Diskhaler(R) and Rotahaler(R) devices was investigated using a twin stage impinger operating at 60 l min(-1).Results. Inhalation performance of binary ordered mixes prepared using BSA-maltodextrin and lactose (63-90 mu m) was improved by addition of FPL and micronised PEG 6000. For the addition of 5% w/w FPL the protein fine particle fraction (0.5-6.4 mu m) using the Diskhaler(R) was increased from 31.7 +/- 2.4% to 47.4 +/- 2.2%. Inclusion of FPL and micronised PEG 6000 changed the bulk properties of inhalation powders and reduced powder flow but did not affect device emptying. Unexpectedly, Improvements in performance were found to be independent of the order of addition of FPL to the ternary powder formulations. SEM studies revealed that this was probably the result of a redistribution of protein particles between the coarse carrier lactose component and added FPL during mixing.Conclusions. Fine particle excipients can be used to improve the performance of carrier-based protein dry powder aerosols. Mechanistically, enhancement of performance is proposed to result from a redistribution of protein particles from coarse carrier particles to the fine particle component in the ternary mix.