Martin Gary P, Marriott Christopher, Zeng Xian-Ming
Pharmaceutical Science Research Division, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
Pharm Res. 2007 Feb;24(2):361-9. doi: 10.1007/s11095-006-9156-5. Epub 2006 Dec 20.
The purpose of the study was to determine how air flow profiles affect fine particle fractions (FPF) (<5 microm) from dry powder aerosol formulations and whether laser diffraction (LD) could be used to measure FPF of aerosols generated by variable flows.
Carrier-based formulations containing 1.5% w/w micronized salbutamol base blended with the 63-90 microm fraction of alpha-lactose monohydrate or sorbitol or maltose were aerosolised from a model glass device using either a constant flow rate or a predetermined flow profile. The FPFs of the same aerosolised particles were first measured by LD and then by a liquid impinger. Volunteer inhalation airflow profiles and 3-phase (acceleration, constant flow rate and deceleration) square wave airflow profiles were generated using the Electronic Lung and an Inhalation Profile Recorder. Similar experiments were conducted for a carrier-free formulation from the Bricanyl Turbohaler.
Salbutamol FPFs of all carrier-based formulations were found to increase by increasing the initial flow increase rate (FIR) from 200 to 600 l min(-1) s(-1) although they could be placed in an increasing order of maltose blend < sorbitol blend < lactose blend. A significant linear correlation was found between FPFs measured by LD and by inertial impaction (R (2) = 0.95, p < 0.01, ANOVA). For the Bricanyl Turbohaler, increasing FIR from 120 to 600 l min(-1) s(-1) for a constant peak flow rate (PFR) of 60 l min(-1) increased the mean Terbutaline FPF from 18.2% to 45.5%. For the volunteer inhalation profiles, a higher FIR tended to be associated with higher PFR, leading to a marked increase in drug FPF due to the combined effect of FIR and PFR.
Drug FPF from either carrier-free or carrier-based formulations is determined by both FIR and PFR. LD is a viable technique to measure the performance of dry powder aerosol formulations at realistic inspiratory flow profiles.
本研究旨在确定气流分布如何影响干粉气雾剂制剂中的细颗粒部分（FPF，<5微米），以及激光衍射（LD）是否可用于测量可变气流产生的气雾剂的FPF。
将含有1.5%w/w微粉化沙丁胺醇碱与63 - 90微米部分的一水合α-乳糖或山梨醇或麦芽糖混合的载体基制剂，使用恒流速率或预定气流分布从模型玻璃装置中雾化。相同雾化颗粒的FPF首先通过LD测量，然后通过液体冲击器测量。使用电子肺和吸入分布记录器生成志愿者吸入气流分布和三相（加速、恒流速率和减速）方波气流分布。对布地奈德都保的无载体制剂进行了类似实验。
发现所有载体基制剂的沙丁胺醇FPF随着初始流速增加率（FIR）从200增加到600升/分钟·秒⁻¹而增加，尽管它们可以按麦芽糖混合物<山梨醇混合物<乳糖混合物的递增顺序排列。通过LD测量的FPF与通过惯性冲击测量的FPF之间发现了显著的线性相关性（R² = 0.95，p < 0.01，方差分析）。对于布地奈德都保，在60升/分钟的恒定峰值流速（PFR）下，将FIR从120增加到600升/分钟·秒⁻¹，使平均特布他林FPF从18.2%增加到45.5%。对于志愿者吸入分布，较高的FIR往往与较高的PFR相关，由于FIR和PFR的联合作用，导致药物FPF显著增加。
无载体或载体基制剂的药物FPF由FIR和PFR共同决定。LD是一种可行的技术，可用于在实际吸气气流分布下测量干粉气雾剂制剂的性能。
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