PDF(Pubmed)
Abstract：
Purpose: An efficient, cost-effective and non-invasive test is required to overcome the challenges faced in the process of bioequivalence (BE) studies of various orally inhaled drug formulations. Two different types of pressurized meter dose inhalers (MDI-1 and MDI-2) were used in this study to test the practical applicability of a previously proposed hypothesis on the BE of inhaled salbutamol formulations. Methods: Salbutamol concentration profiles of the exhaled breath condensate (EBC) samples collected from volunteers receiving two inhaled formulations were compared employing BE criteria. In addition, the aerodynamic particle size distribution of the inhalers was determined by employing next generation impactor. Salbutamol concentrations in the samples were determined using liquid and gas chromatographic methods. Results: The MDI-1 inhaler induced slightly higher EBC concentrations of salbutamol when compared with MDI-2. The geometric MDI-2/MDI-1 mean ratios (confidence intervals) were 0.937 (0.721-1.22) for maximum concentration and 0.841 (0.592-1.20) for area under the EBC-time profile, indicating a lack of BE between the two formulations. In agreement with the in vivo data, the in vitro data indicated that the fine particle dose (FPD) of MDI-1 was slightly higher than that for the MDI-2 formulation. However, the FPD differences between the two formulations were not statistically significant. Conclusion: EBC data of the present work may be considered as a reliable source for assessment of the BE studies of orally inhaled drug formulations. However, more detailed investigations employing larger sample sizes and more formulations are required to provide more evidence for the proposed method of BE assay.
摘要：
目的：高效，为了克服各种口服吸入药物制剂的生物等效性（BE）研究过程中面临的挑战，需要具有成本效益和非侵入性的测试。在这项研究中使用了两种不同类型的加压仪表剂量吸入器（MDI-1和MDI-2），以测试先前提出的关于吸入沙丁胺醇制剂BE的假设的实际适用性。方法：使用BE标准比较从接受两种吸入制剂的志愿者收集的呼出气冷凝液（EBC）样品的沙丁胺醇浓度曲线。此外,吸入器的空气动力学粒度分布是通过使用下一代冲击器确定的。使用液相和气相色谱法测定样品中的沙丁胺醇浓度。结果：与MDI-2相比，MDI-1吸入器诱导的沙丁胺醇EBC浓度略高。最大浓度的几何MDI-2/MDI-1平均比（置信区间）为0.937（0.721-1.22），EBC时间曲线下面积为0.841（0.592-1.20），表明两种配方之间缺乏BE。与体内数据一致，体外数据表明MDI-1的细颗粒剂量(FPD)略高于MDI-2制剂。然而,两种制剂之间的FPD差异无统计学意义.结论：本工作的EBC数据可被认为是评估口服吸入药物制剂的BE研究的可靠来源。然而,需要采用更大样本量和更多配方的更详细的调查,以便为拟议的BE测定方法提供更多证据.
