技術(shù)cfd通過模擬實(shí)現(xiàn)干粉吸入器的性能優(yōu)化

1、CFD simulations help optimise the performance of a dry powder inhalerBy A.H. de Boer and P. Hagedoorn of the Department of Pharmaceutical Technology and Biopharmacy of the University of Groningen (The Netherlands), and R. Woolhouse and J. Tibbatts, ANSYS Fluent Europe .In recent years the as been a

2、significant and growing interest in dry powder inhalers (DPIs). The clinical applications for DPIs now extend well beyond the treatment of lung diseases such as asthma, COPD and cystic fibrosis. Recently significant media coverage has been given to the introduction of inhaled diabetic insulin, and s

3、ignificant research is currently being carried out to develop methods for the delivery of biotics and vaccines as dry powders. In order to develop a drug for delivery as a dry powder two significant hurdles need to be overcome:1. The drug must be stabilised in a dry state and as particles with an ae

4、rodynamic diameter in the range 1 to 5 microns2. A suitable dry powder inhaler (DPI) must be developed which will deliver the primary drug particles to the inhaled airAs a result of their research in this area the University of Groningen have developed a disposable DPI for the delivery of high drug

5、doses, the TwincerTM. Tests have shown that the TwincerTM is capable of delivering 60 mg doses of pure micronised colistin sulfomethate (drug) in a single inhalation.The TwincerTM, shown in Figure 1, consists primarily of two parallel classifiers and a bypass flow channel. Each classifier has three

6、tangential ports which generate a swirling flow within the classifier; one port delivers air from the classifier inflow, a second delivers air and entrained drug particles from the drug inflow, and a third port delivers air from the bypass channel. Air and particles leave the classifiers through a s

7、mall opening in the base of the classifier where they join the bypass air and continue into the mouthpiece.The drug particles entrained into the airflow from the blister will not at this stage be individual particles. Particles of this scale are likely to join together into cohesive particle agglome

8、rates. The aim of the classifiers in the TwincerTM is to subject the particle agglomerates to inertial and shear forces in order to break-up the particle agglomerates. The aim of the bypass channel is to reduce the pressure loss of the device and therefore to control the inspiratory effort required

9、from the patient. The performance of the inhaler is assessed in three ways, the delivered fine particle fraction (FPF) of the device, the particle retention within the device, and the pressure drop characteristics of the device.Experimental observations of the TwincerTM have shown that minute change

10、s in geometric s can have a significnfluence on the inhaler performance. To further understand the behaviour of the device and the reasons for these sensitivities a number of CFD studies werecarried out using FLUENT.The CFD results for pressure loss were comparedexperiment measurements tovalidate th

11、e m. The results of both the CFD and experimental work are shown in Figure 2 and show good agreement. The predicted particle trajectories shown in Figure 3 also agreewell with experimental observations. Experimental observations have shown that the classifier cut-point is typically between 5 and 7 m

12、icrons, depending on the drug properties. The particle trajectories of Figure 3 show that 10 micron particles are predicted to be retained within theclassifiers whereas 1 micron particles transit out of the classifiers and into the mouthpiece. In addition the image of Figure 4 shows that larger swee

13、per particles (approximately 60 microns) are retained within the classifiers during experimental testing.Since the design aim of the TwincerTM device is tiver high drug doses, the flow splitwithin the device is of key importance. Theum dose that can be delivered by thedevice is related to the percen

14、tage of the total flow rate that passes through the drug inflow, and the patients lung capacity, which may potentially be impairedThe CFD results showed that only 16% of the total airflow passed through the drug inflow, and that 60% of the airflow by-passed the classifiers completely. These flow spl

15、its remained roughly constant over the expected operating range of the device. To try to improve the flow split a further CFD simulation was carried out where a blockage was introduced into the bypass channel, initially using a porous media approach. Partially blocking the bypass channel was found t

16、o reduce the total airflow without affecting the mass flow available to mobilise the drug and to generate swirl within the two classifiers. It is inferred from this that such a design change is unlikely to affect the rate of entrainment from the blister, or the rate of agglomerate break-up in the cl

17、assifier. However such a change may alter the deposition in the peripheral lung.The CFD study also showed that the inlet port to the classifier from the bypass channel did not carry any flow. This can be seen in the vector plot of in Figure 5 where the relev nlet is marked as “dead flow channel”. Pr

18、eviously unexplained experimental observations had shown that an accumulation of particles often occurred in these flow channels. A further CFD simulation was carried out with these flow channels removed. As expected the results of the simulation showed that the removal of these flow channels had no

19、 signific mpact on the behaviour of the device.The use of CFD in the development of the TwincerTM DPI has alloweded assessment ofthe flow behaviour within the inhaler. The results from the CFD showed good agreement with experimental results and observations, and the information gained from the CFD has guided design modifications to both the classifier inlet channels and the bypass