Cui Yingtong, Huang Ying, Zhang Xuejuan, Lu Xiangyun, Xue Jun, Wang Guanlin, Hu Ping, Yue Xiao, Zhao Ziyu, Pan Xin, Wu Chuanbin
School of Pharmaceutical Science, Jinan University, Guangzhou 510006, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Acta Pharm Sin B. 2022 Jan;12(1):437-450. doi: 10.1016/j.apsb.2021.06.011. Epub 2021 Jun 21.
Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.
干粉吸入器(DPIs)由于能够直接将药物输送至肺部、药物稳定性良好且患者依从性令人满意,已在肺部疾病治疗中得到广泛应用。然而,对肺部给药过程(PDPs)的认识不够清晰阻碍了干粉吸入器的发展。当前大多数评估方法采用过度简化的模型来探究肺部给药过程,导致对整个或部分肺部给药过程的研究并不完整。在本研究中,一个创新的模块化过程分析平台(MPAP)被用于研究不同载体粒径(CPS)的干粉吸入器各肺部给药过程的详细机制。该MPAP由激光粒度分析仪、吸入器装置、人工喉和预分离器组成,用于研究干粉吸入器的流化与分散、输送、分离和沉积过程。实时监测药物释放曲线、药物聚集情况和载体情况。探究了载体粒径对肺部给药过程的影响及其相应机制。通过光学轮廓仪和弗里曼技术四轴粉末流变仪研究了载体的粉末特性。采用下一代撞击器探究干粉吸入器的雾化性能。新型MPAP成功应用于探究肺部给药过程的综合机制,在干粉吸入器的研究与开发方面具有巨大的应用潜力。