Department of Pharmacy and Pharmaceutical Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom.
Inhalation Consultancy Ltd., Tarn House, 77 High St., Yeadon, Leeds LS19 7SP, United Kingdom.
Eur J Pharm Sci. 2019 Nov 1;139:105059. doi: 10.1016/j.ejps.2019.105059. Epub 2019 Aug 28.
Dry powder inhalers (DPIs) are passive devices used to administer inhaled medication for the management of asthma and chronic obstructive pulmonary disease (COPD). DPIs require patients to generate a sufficient internal turbulent airflow force during each inhalation to deaggregate the powdered drug formulation into an emitted dose containing particles with the greatest likelihood of lung deposition. This internal force is generated by the interaction between the user's inhalation flow and the resistance of the DPI. Traditional compendial in vitro methods of measuring dose emission use a vacuum pump to simulate inhalation. We have adapted this in vitro method by replacing the square wave inhalation profile generated by a vacuum pump with the inhalation profiles of patients using an empty DPI. This method enables accurate assessment of the actual dose they would have inhaled. In the present study, real-life inhalation profiles were selected from 15 patients with COPD who inhaled through an empty placebo Spiromax® DPI. Ex vivo dose emissions were measured for the medium (emitted dose of 160 μg/4.5 μg) and high-strength (320 μg/9 μg) budesonide/formoterol formulations from the Spiromax DPI. These profiles were used to investigate the effect of the primary inhalation parameter-peak inhalation flow (PIF). Some profiles were modified to isolate other inhalation parameters (namely, inhaled volume [V] and acceleration rate of the inhalation maneuver [ACIM]). Both the medium-strength and high-strength DuoResp Spiromax displayed flow-dependent dose emission. When the PIF of a patient's inhalation maneuver increased from 26.8 L/min to 69.7 L/min, there was a significant (p < 0.05) effect on the dose-emission characteristics of the medium-strength and high-strength DuoResp Spiromax. At each PIF, an increase in V from approximately 500 mL to 2000 mL had no effect on the dose-emission characteristics of either strength. However, at each V there was a significant (p < 0.05) effect on the dose-emission characteristics as PIF increased. The effect of ACIM on the dose-emission characteristics was small. The ex vivo methodology used in this study provides a practical approach to identify the actual dose a patient might inhale during routine real-life use of the DuoResp Spiromax.
干粉吸入器（DPIs）是一种被动设备，用于管理哮喘和慢性阻塞性肺疾病（COPD）的吸入药物。DPIs 要求患者在每次吸入时产生足够的内部湍流气流力，以使粉末药物制剂解聚成含有最有可能肺部沉积的颗粒的发射剂量。这种内力是通过用户吸入气流与 DPI 阻力之间的相互作用产生的。传统的药典体外测量剂量释放的方法使用真空泵来模拟吸入。我们通过用患者的吸入轮廓代替真空泵产生的方波吸入轮廓来适应这种体外方法，使用空的 DPI。这种方法可以准确评估他们实际吸入的剂量。在本研究中，从 15 名使用空的安慰剂 Spiromax®DPI 吸入的 COPD 患者中选择真实生活中的吸入轮廓。对来自 Spiromax DPI 的中强度（发射剂量 160μg/4.5μg）和高强度（320μg/9μg）布地奈德/福莫特罗制剂进行体外剂量排放测量。这些轮廓用于研究主要吸入参数-峰值吸入流量（PIF）的影响。一些轮廓被修改以分离其他吸入参数（即吸入量[V]和吸入动作的加速度率[ACIM]）。中强度和高强度 DuoResp Spiromax 均显示出流量依赖性剂量释放。当患者吸入动作的 PIF 从 26.8 L/min 增加到 69.7 L/min 时，中强度和高强度 DuoResp Spiromax 的剂量释放特性有显著（p<0.05）影响。在每个 PIF 下，从大约 500mL 增加到 2000mL 对任何强度的剂量释放特性都没有影响。然而，在每个 V 下，随着 PIF 的增加，剂量释放特性有显著（p<0.05）影响。ACIM 对剂量释放特性的影响很小。本研究中使用的体外方法提供了一种实用方法，可以识别患者在常规真实生活中使用 DuoResp Spiromax 时可能吸入的实际剂量。
