Richardson Catherine H, de Matas Marcel, Hosker Harold, Mukherjee Rahul, Wong Ian, Chrystyn Henry
Institute of Pharmaceutical Innovation, University of Bradford, Bradford, BD7 1DP, UK.
Pharm Res. 2007 Nov;24(11):2008-17. doi: 10.1007/s11095-007-9328-y. Epub 2007 May 18.
The relative lung bioavailability of salbutamol sulfate particles produced using supercritical fluids (SEDS) and delivered by dry powder inhaler (DPI) was compared with the performance of a conventional micronized drug DPI using the same device design (Clickhaler, Innovata Biomed).
Twelve healthy volunteers and 11 mild asthmatic patients completed separate four-way randomised cross-over studies, assessing the relative bioavailability of salbutamol sulfate (urinary excretion method), formulated as SEDS particles (three batches) and micronized particles (Asmasal inhaler, UCB Pharma Ltd). Post-treatment improvements in patient lung function were assessed by measuring FEV(1). Physicochemical evaluation of the three SEDS batches revealed inter-batch differences in particle size and shape.
There was no significant difference in the relative lung bioavailability of salbutamol and its bronchodilator response between the best performing SEDS formulation and the Asmasal inhaler in volunteers and patients, respectively. SEDS salbutamol sulfate showing wafer like morphology gave greater fine particle dose, relative lung bioavailability and enhanced bronchodilation compared to other SEDS batches containing elongated particles.
Active Pharmaceutical Ingredient (API) manufactured using supercritical fluids and delivered by DPI can provide similar lung bioavailability and clinical effect to the conventional micronized commercial product. Product performance is however notably influenced by inter-batch differences in particle characteristics.
将使用超临界流体（SEDS）制备并通过干粉吸入器（DPI）递送的硫酸沙丁胺醇颗粒的相对肺生物利用度，与使用相同装置设计（Clickhaler，Innovata Biomed）的传统微粉化药物DPI的性能进行比较。
12名健康志愿者和11名轻度哮喘患者完成了单独的四向随机交叉研究，评估硫酸沙丁胺醇（尿排泄法）的相对生物利用度，该药物制成SEDS颗粒（三批）和微粉化颗粒（Asmasal吸入器，UCB制药有限公司）。通过测量第一秒用力呼气容积（FEV₁）评估治疗后患者肺功能的改善情况。对三批SEDS颗粒的物理化学评估显示批次间粒径和形状存在差异。
在志愿者和患者中，表现最佳的SEDS制剂与Asmasal吸入器相比，沙丁胺醇的相对肺生物利用度及其支气管扩张反应分别无显著差异。与其他含有细长颗粒的SEDS批次相比，呈薄片状形态的SEDS硫酸沙丁胺醇具有更高的细颗粒剂量、相对肺生物利用度和更强的支气管扩张作用。
使用超临界流体制造并通过DPI递送的活性药物成分（API）可提供与传统微粉化商业产品相似的肺生物利用度和临床效果。然而，产品性能受颗粒特性批次间差异的显著影响。
