Seeing is believing: using optical diagnostics to investigate MDI sprays and DPI fluidization

Inhaler device modifications directly influence aerosol generation mechanisms, so the development of inhalation products could be advanced effectively if the relevant processes can be studied in situ. However, the ability to visualize, in real time, atomization in a metered dose inhaler (MDI) or fluidization in a dry powder inhaler (DPI) remains challenging. This article reviews high-speed imaging, fluorescence imaging, particle image velocimetry (PIV) and phase-doppler anemometry (PDA) and demonstrates how these techniques can be used to characterize aerosol clouds whilst they are being generated and reveal the nature of aerosol production processes as they unfold inside inhaler devices. The different optical diagnostics generate complementary data including aerosol droplet size, velocity and overall aerosol/spray attributes. Understanding the details of transient events during metering of a drug dose into the inhaled airflow at the appropriate temporal and spatial resolution creates opportunities for targeted interventions to solve problems e.g. excessive device deposition. Moreover, the images generated by optical techniques represent a readily accessible form of information which supports multi-disciplinary collaboration, so, when using optical diagnostics, we can legitimately claim that “Seeing is Believing”

A study of factors affecting nucleation and bubble growth in pressurised metered dose inhalers

Various hypotheses have been introduced to explain disintegration of the continuous liquid phase into individual droplets leading to spray formation in pressurised metered dose inhalers (pMDIs). In a practicable system, the liquid formulation to be discharged from the pressurised container needs to be nucleated to ensure spray generation. Nucleation can be described as the generation of a nucleus of the vapour phase within the bulk liquid. As a stable nucleus is formed, it grows significantly and then detaches from its nucleation site to move upwards in the liquid phase. In our research, the effects of various parameters on the nucleation of HFA227 was analysed with the aim of gaining a better understanding of bubble formation and the nucleation process in HFA propellants, including the surface geometrical properties, actuator orifice size and the mass flow rate through the orifice. Other important factors influencing the nucleation process that were considered comprised the viscosity and surface tension of the formulation, thermodynamic state variables including temperature, pressure and degree of superheat. The results highlighted the effect of surface imperfections on the rate of nucleation and bubble growth. A comparison of two different orifice sizes was made and a significant change in the shape and motion of the bubbles was observed. An intense nucleation was also observed at higher mass flow rate of HFA227 through the valve. It is anticipated that recognising the factors affecting nucleation and bubble growth of HFA227 may lead to potential routes of influencing the medical aerosol generation mechanism inside the pMDI and control the fine particle size distribution

Effect of geometry on the performance of intermingling nozzles

This study investigates the effect of nozzle geometry on the intermingling process. The dimensions of intermingling nozzles with single air inlets extended across the width of a rectangular yam channel are systematically varied. Nozzles with this cross-sectional shape prove to be easy to manufacture and efficient at intermingling. The performance is evaluated by visually inspecting the intermingled yarns and by measuring the nip fre quency. We have found that the performance of nozzles with large inlet widths is weakly dependent on yam channel geometry. The performance of nozzles with the smallest air inlet widths, on the other hand, is sensitive to yarn channel geometry. The smallest and largest yam channels we have considered give poor intermingling results. Control of the yam path is beneficial for the success and consistency of the intermingling process. Using yam guides to create a diagonal yarn path across the nozzle has the additional advantage of decreasing noise production. Our extended air inlet slot ensures continuous exposure of the yarn to the supply air stream across the entire width of the yarn channel in this arrangement. We also compare our designs with four industrial nozzles under identical process conditions. This study reveals similar trends for nip frequency and power consumption. The results agree with the broad trend established in the geometry study that the shape of the yam channel is not critical, provided the air inlet is large enough

Effects of geometry on the flow characteristics and texturing performance of air-jet texturing nozzles

Air-jet texturing is a versatile process for producing a range of synthetic yarns with a spun-like appearance, which are widely used for apparel and furnishing fabrics and industrial textiles.There is no universal nozzle capable of processing any supply yam of any linear density.The role played by nozzle geometry is still not fully understood.The experimental study presented here seeks to compare air flow characteristics and texturing data for nine nozzles under realistic texturing conditions as a basis for an improved understanding of the effect of nozzle geometry.Compressed air consumption results show that the nozzle flow is choked at air inlets; thus the nozzles behave as converging-diverging passages.The exit flow distribution is approximately axisym metric in all cases.Nozzle exit flow characteristics are typical of underexpanded jets with a ratio of jet exit plane static pressure to ambient pressure smaller than or equal to approximately 2.Textured yams with varying visual appearance were produced by different nozzles under identical processing conditions.Nevertheless, the strength properties of the yams were broadly the same, as was their increase in linear density.Of all test variables, the tension in the stabilizing zone was the only quantity to show some promise as a correlating parameter with texturing quality.Neither the presence of shock waves in the exit region nor the magnitude of the exit zone velocity correlated with texturing effectiveness.The texturing results of these trials highlight the fact that the current descriptions of air-jet texturing are not fully capable of explaining the subtle effects due to nozzle geometry and can at best be described as incomplete

Application of filtration blocking models to describe fouling and transmission of large plasmids DNA in sterile filtration

Sterile filtration is considered as a final step in processing pharmaceutical grade plasmid DNA. During the development of the filtration process, fundamental understanding on the mechanism of fouling is critical to improve filtration operations. The mechanism of fouling of pQR150 (20 kb) and pGEc47 (56 kb) plasmids DNA during constant pressure filtration inside 0.22 μm PVDF membrane is experimentally investigated. The decline of filtrate flux as a function of time is analysed using the framework of classical and combined blocking models. The results for both plasmids indicate a transition between fouling mechanisms. Initially, during the early part of the filtration, the intermediate blocking model provided the best fit of the experimental results suggesting that fouling of the membrane was mainly caused by deposition of particles onto its surface. Afterwards, the result trends were best captured by the standard blocking model indicating that internal fouling of the membrane was the dominant fouling mechanism. A study of the transmission of both plasmids shows a significant reduction of plasmid transmission which coincides with the transition of the fouling mechanism from intermediate to standard blocking. The study highlights how the fouling behaviour of large plasmid DNA during sterile filtration is determined by the complex interplay between the flexibility of the molecules and the internal structure of the membrane

Effect of nozzle geometry on air-jet texturing performance

This paper systematically investigates the effect of a number of geometric parameters on the texturing performance of air-jet texturing nozzles. In order to facilitate the research, an air-jet texturing nozzle with a rectangular cross section has been developed. The texturing performance of the nozzles is assessed by means of process observations and on-line measurement of stabilizing zone tension, and also by measuring the in creased linear density of the yams on textured yarn samples. Furthermore, instability, elongation at break, and tenacity are measured, and texturing quality is judged by visual inspections and examination of scanning electron microscopy images of the textured yarns. Tension in the stabilizing zone, increase in linear density, and to a somewhat lesser extent instability are reliable measures of texturing quality. The best texturing comes from nozzles with a slightly diverging main channel and a single air inlet hole located far from the nozzle exit. A curved diverging exit profile is essential for successful texturing. The results of the tests to determine the effect of air inlet angk are inconclusive and require further investigation

Outcome of a questionnaire within European pharmaceutical aerosol group (EPAG) companies concerning the implementation of the abbreviated impactor measurement (AIM) concept for the assessment of orally inhaled product (OIP) aerosol aerodynamic particle size properties

The AIM Concept as an augmentation of full resolution cascade impactor (CI) measurements of the aerodynamic properties of aerosols emitted by OIPs has been in existence for about ten years. A previous EPAG-based survey undertaken five years ago indicated significant interest in the approach, particularly for the screening of candidate products in early stage product development. We report the outcome of a further questionnaire with the goals of establishing: (a) the types of AIM-based equipment currently in use; and (b) insight into perceived hurdles towards full implementation within the product lifecycle. Responses were received in October 2016 from 17 out of 22 organizations from people involved directly with the in vitro testing of pressurized metered dose inhaler (pMDI) and dry powder inhaler (DPI) products. The survey has shown that the AIM concept has sufficient popularity within the EPAG respondent organizations to be considered a viable augmentation to existing full resolution CI methodology. The main conclusions are: (1) The Fast Screening Andersen (FSA), reduced Next Generation Impactor (rNGI) and Fast Screening Impactor (FSI) are all used as AIM-based impactor configurations for both dry powder inhaler (DPI) and pressurized metered dose inhaler (pMDI) applications; (2) AIM-based methods are used almost entirely for the early development phase of the OIP life cycle; (3) Organizations in general do not have confidence to use the AIM concept more widely in the product life cycle whilst no compendial/regulatory guidance is available to provide standard procedures and precautions/regulatory acceptance respectively

A study of factors affecting nucleation and bubble growth in pressurised metered dose inhalers [Abstract]

A study of factors affecting nucleation and bubble growth in pressurised metered dose inhalers [Abstract

Calculation of radiative heat transfer in combustion systems

Most practical combustion systems involve complex geometry configurations and CFD techniques used for the calculation of flow and combustion in such geometries use body-fitted non-orthogonal mesh systems. This paper reviews some of the currently available radiative heat transfer calculation techniques suitable for such CFD applications. The Monte Carlo method, the discrete transfer method, the YIX method, the discrete ordinates method and the finite volume method are discussed and some notable applications related to combustion problems are reviewed. Comparative results using all the methods outlined are presented for bench mark problems and their applicability to complex geometry situations are discussed. Radiative heat flux predictions for an S.I. engine simulation are presented to demonstrate the capability of the discrete transfer method in a pent-roof complex geometry combustion chamber. The paper also describes a ray based technique for the handling of turbulence-radiation interactions in combustion and its application is demonstrated in the prediction of a methane diffusion flame

Development of a theoretical model to predict pMDI spray force, using alternative propellant systems

Continued success in the treatment of asthma and COPD requires new pMDI propellants for delivering aerosols with good patient comfort and acceptable levels of oral cavity deposition. The purpose of this work is to develop a theoretical model capable of predicting pMDI spray force as a function of metering valve geometric parameters and different propellant systems: HFA134a, HFA227ea and HFA152a. Such theoretical tool can be used in combination with lab-based measurements for device characterisation and potentially to reduce the number of experimental trials. The outcome of the model is compared against measurements of plume force with Copley Scientific Spray Force Tester SFT 1000. Results suggest that the size of the spray orifice has a significant direct effect on the spray force. We have also observed HFA134a and HFA152a generates similar magnitude of spray force and velocity where HFA227ea generates the lowest velocity and force values. These findings could potentially mean HFA152a sprays are expected to show similar levels of mouth-throat deposition to HFA134a sprays rather than HFA227ea sprays