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 deliv...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.展开更多
The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmona...The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmonary drug delivery with references to fluidization research, in particular, studies on Geldart group C powders. Dry powder inhaler device-formulation combination has been shown to be an effective method for delivering drugs to the lung for treatment of asthma, chronic obstructive pulmonary disease and cystic fibrosis. Even with advanced designs, however, delivery efficiency is still poor mainly due to powder dispersion problems which cause poor lung deposition and high dose variability. Drug particles used in current inhalers must be 1–5 μm in diameter for effective deposition in small-diameter airways and alveoli. These powders are very cohesive, have poor flowability, and are difficult to disperse into aerosol due to cohesion arising from van der Waals attraction. These problems are well known in fluidization research, much of which is highly relevant to pulmonary drug delivery.展开更多
基金funded by the Fundamental Research Funds for the Central Universities(Nos.21620434 and 2162014,China)the National Natural Science Foundation of China(Nos.81673375 and 81703431)+1 种基金the Science and Technology Foundation Guangzhou(No.201509030006,China)the National Students Innovation Training Program of China(No.201901390,China)。
文摘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.
文摘The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmonary drug delivery with references to fluidization research, in particular, studies on Geldart group C powders. Dry powder inhaler device-formulation combination has been shown to be an effective method for delivering drugs to the lung for treatment of asthma, chronic obstructive pulmonary disease and cystic fibrosis. Even with advanced designs, however, delivery efficiency is still poor mainly due to powder dispersion problems which cause poor lung deposition and high dose variability. Drug particles used in current inhalers must be 1–5 μm in diameter for effective deposition in small-diameter airways and alveoli. These powders are very cohesive, have poor flowability, and are difficult to disperse into aerosol due to cohesion arising from van der Waals attraction. These problems are well known in fluidization research, much of which is highly relevant to pulmonary drug delivery.
