Jalili, Vahid (2004) Application of CFD in designing a drug delivery mixing chamber: an experimental and computational study. PhD thesis, University of Greenwich.

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Abstract

The purpose of this novel research was to understand the flow behaviour and improve the efficiency of the Volumatic™ spacer, using a combination of engineering tools such as CFD, Laser Doppler Anemometry (LDA) and Row visualization techniques. The lack of information on the Volumatic /A/ spacer meant that, initial understanding had to be gained into the flow behaviour within the spacer. This was initially performed by injecting air carrying a tracer concentration to represent t li<^drug portion of the medicine. The efficiency (volume of drug collected at the mouth piece) was found to be about 6.5% which was in the same order as the figure quoted in the literature Chuffart A series of parametric studies were carried out to discover the effects of various parameters on The overall efficiency of the spacer. In the initial part a series of jet profiles were studied at the inlet, these were in the shape of straight, cone shape and spray jet profiles. It was concluded that the jet with a cone angle of 5° increased the efficiency of the spacer from G.5% to 9.4%.

The next stage of parametric study involved reducing the length of the spacer from 0.24 m to 0.12 m and varying the inlet velocity from 40 m/s down to 10 m/s. The findings concluded that t in1 efficiency of the spacer could be increased to 23%, using a velocity of 40 m/s at inlet. The length was reduced from 0.12 m to 0.06 m and a similar study as described above was carried out. This time it was concluded that reducing the velocity to 30 m/s increased the efficiency to 30%. The other interesting feature to come out of this study was that the whole of tIk1 spacer volume was used, hence the drug was mixing better than in the original Volumatic /A/ spacer, where about one third of the spacer volume remained completely empty of the drug.

The studies carried out so far had shown that the additional increase in drug delivery efficiency in the case of the Volumatic 7 A/ spacer, was not substantial enough to justify the considerable manufacturing costs which have to be met, if the Volumatic 7 A/ spacer was to be remanufactured in its improved design. The way forward seemed to be in the development of a new design. The new design had to be small enough, so that it could be carried around easily by patients, who do not use1 the current spacer due to its size. The new design had to be economical in terms of manufacture, simple to use and easy to clean. The reasons mentioned above and the current trend towards the tube type spacer designs, implied the logical approach would be to base the design on a similar geometry. A tube type spacer was modelled with two holes drilled directly opposite each other, a distance of 10 mm away from the pMDI's nozzle. The holes introduced a pressure difference, hence directing the drug towards the patient's airway system. The new spacer had a length of 0.1 m. The computational results showed that the efficiency had increased to 71% for this particular design.

The CFD results obtained from the initial study on the Volumatic 7 M spacer were validated using LDA measurements. The velocities along four different locations were measured. At each location the velocities were measured at increments of 5 mm for a distance of 50 mm inside the spacer. The LDA results showed very good agreements with those obtained from CFD. The volume of data sampled experimentally at each point was 25,000 data points. This large volume of data eliminated any random sources of error, and as the CF D simulations were carried out some six months prior to LDA results, it was safe to assume that the drug had been modelled accurately. The same experimental set up was used to measure velocity values for the tube spacer, but in this instance, velocity measurements were made only along two planes, due to limited time and availability of the drug source.

Finally laser light sheeting was used to illuminate the Volumatic T spacer and a high speed KODAK camera capable of capturing 4500 frames per second was used. The visualization study proved that there was a portion of the Volumatie /A/ spacer which at times was free of any drug.

The originality of the work has been described in the following paragraph: Prior to this research there was no comprehensive study available combining engineering tools such as Computational Fluid Dynamics (CFD), Laser Doppler Anemoinetry (LDA) and High Speed Photography to study the (low pattern within the current Volumatic /A/ spacer design and hence analysing its efficiency. The studies carried out were of the impaction type. The results of this study have confirmed that there are several parameters contributing to the efficiency of the Volumatic' A/ spacer. This knowledge was not available in the open literature previously.

The initial part of this study has provided a scientific approach to analysing the flow patterns, hence obtaining an accurate value for the efficiency of the current device. This part of the study alone is a valuable tool for industry, because it has given industry data which has not been previously available. The results from this study have indicated that, the Aero Chamber Spacer type design has an efficiency of 71% compared to the current 10% efficiency of the Volumatic 7 A/ spacer. The efficiencies discussed are measured in terms of the percentage of the drug delivered to the mouth piece. The benefit to industry would be saving at a conservative estimate in terms of millions of Pounds annually. This can be calculated from industry's own figures that, 1 out of every 5 new born baby suffers from asthma in various degrees. The drug is the most expensive component of the device, hence a more efficient device would use a lesser quantity of the drug.

Finally the combination of techniques used, and the number of data samples taken for example in the case of LDA measurements some 25000 data samples were taken and averaged at each point, has ensured a high degree of accuracy and confidence in the results presented.

Item Type:	Thesis (PhD)
Additional Information:	uk.bl.ethos.401594 This research programme was carried out in collaboration with Astra Zeneca Pharmaceutical Company.
Uncontrolled Keywords:	computational fluid dynamics, CFD, drug delivery, numerical analysis, Laser Doppler Anemometry, LDA, velocity
Subjects:	Q Science > QC Physics R Medicine > RS Pharmacy and materia medica T Technology > TA Engineering (General). Civil engineering (General)
Pre-2014 Departments:	School of Computing & Mathematical Sciences School of Computing & Mathematical Sciences > Centre for Numerical Modelling & Process Analysis
Last Modified:	29 Aug 2018 13:41
URI:	http://gala.gre.ac.uk/id/eprint/6196

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