Wiegandt Felix C, Froriep Ulrich P, Müller Fabian, Doll Theodor, Dietzel Andreas, Pohlmann Gerhard
Division of Translational Biomedical Engineering, Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, 30625 Hannover, Germany.
Department of Otorhinolaryngology, Hannover Medical School, 30625 Hannover, Germany.
Pharmaceutics. 2021 May 4;13(5):657. doi: 10.3390/pharmaceutics13050657.
A major disadvantage of inhalation therapy with continuous drug delivery is the loss of medication during expiration. Developing a breath-triggered drug release system can highly decrease this loss. However, there is currently no breath-triggered drug release directly inside the patient interface (nasal prong) for preterm neonates available due to their high breathing frequency, short inspiration time and low tidal volume. Therefore, a nasal prong with an integrated valve releasing aerosol directly inside the patient interface increasing inhaled aerosol efficiency is desirable. We integrated a miniaturized aerosol valve into a nasal prong, controlled by a double-stroke cylinder. Breathing was simulated using a test lung for preterm neonates on CPAP respiratory support. The inhalation flow served as a trigger signal for the valve, releasing humidified surfactant. Particle detection was performed gravimetrically (filter) and optically (light extinction). The integrated miniaturized aerosol valve enabled breath-triggered drug release inside the patient interface with an aerosol valve response time of <25 ms. By breath-triggered release of the pharmaceutical aerosol as a bolus during inhalation, the inhaled aerosol efficiency was increased by a factor of >4 compared to non-triggered release. This novel nasal prong with integrated valve allows breath-triggered drug release directly inside the nasal prong with short response time.
持续给药的吸入疗法的一个主要缺点是呼气时药物损失。开发一种呼吸触发式药物释放系统可以大幅减少这种损失。然而，由于早产儿呼吸频率高、吸气时间短和潮气量低，目前尚无直接在患者接口（鼻叉）内实现呼吸触发式药物释放的产品。因此，需要一种在患者接口内直接释放气溶胶的集成阀门的鼻叉，以提高吸入气溶胶的效率。我们将一个小型化的气溶胶阀集成到一个鼻叉中，由一个双冲程气缸控制。使用用于接受持续气道正压通气（CPAP）呼吸支持的早产儿的测试肺模拟呼吸。吸入气流用作阀门的触发信号，释放加湿的表面活性剂。通过重量法（过滤器）和光学法（光消光）进行颗粒检测。集成的小型化气溶胶阀能够在患者接口内实现呼吸触发式药物释放，气溶胶阀响应时间<25毫秒。通过在吸气期间以团注形式呼吸触发式释放药物气溶胶，与非触发式释放相比，吸入气溶胶效率提高了>4倍。这种带有集成阀门的新型鼻叉允许在鼻叉内直接进行呼吸触发式药物释放，响应时间短。
