Young Paul M, Chan Hak-Kim, Chiou Herbert, Edge Stephen, Tee Terence H S, Traini Daniela
Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
J Pharm Sci. 2007 May;96(5):1331-41. doi: 10.1002/jps.20933.
The influence of processing on the performance of carrier material used in dry powder inhalers was investigated. alpha-Lactose monohydrate crystals were processed by ball milling for cumulative time durations and their properties evaluated. As expected, milling reduced the median particle diameter while increasing fine particulate (<10 microm) and amorphous levels. Recrystallization of these partially amorphous samples resulted in a reduction in fines, elimination of amorphous material with little change in median diameter. To study the effects of processing on aerosolization performance, blends of lactose monohydrate with a model drug (nedocromil sodium trihydrate), were evaluated using an in vitro multistage liquid impinger (MSLI) model. In general, milling and storage of the carriers at high humidity (prior to blending) had a significant (ANOVA, p < 0.05) effect on the fine particle fractions (FPF; <6.8 microm). These effects were attributed predominantly to the fines content, showing a strong correlation between increased fines and FPF (R(2) = 0.974 and 0.982 for milled and recrystallized samples, respectively). However, this relationship only existed up to 15% fines concentration, after which agglomerate-carrier segregation was observed and FPF decreased significantly. These results suggest that, after processing, high-dose drug formulation performance is dominated by the presence of fines.
研究了加工过程对干粉吸入器中所用载体材料性能的影响。对α-乳糖一水合物晶体进行了不同累积时长的球磨处理，并对其性能进行了评估。正如预期的那样，球磨减小了中位粒径，同时增加了细颗粒（<10微米）和无定形物的含量。这些部分无定形样品的重结晶导致细粉减少，无定形物质消除，而中位直径变化不大。为了研究加工过程对雾化性能的影响，使用体外多级液体撞击器（MSLI）模型对乳糖一水合物与一种模型药物（三水合奈多罗米钠）的混合物进行了评估。一般来说，载体在高湿度下（混合前）进行球磨和储存对细颗粒分数（FPF；<6.8微米）有显著影响（方差分析，p<0.05）。这些影响主要归因于细粉含量，细粉增加与FPF之间存在很强的相关性（研磨和重结晶样品的R²分别为0.974和0.982）。然而，这种关系仅在细粉浓度达到15%之前存在，之后观察到团聚体与载体分离，FPF显著下降。这些结果表明，加工后，高剂量药物制剂的性能主要受细粉存在的影响。
