Professor Hak-Kim Chan
Bench to market
Mannitol aerosols for more precise asthma diagnosis. Professor Chan played a pivotal role in the development of dry powder mannitol aerosols for the diagnosis and delivery of drugs for asthma, and the delivery of drugs for impaired mucociliary clearance in diseases such as cystic fibrosis, bronchiectasis and chronic bronchitis [5,7]. The product (Aridol(TM), Pharmaxis Ltd) for asthma diagnosis has recently been approved for sale in Australia, Sweden, Denmark and the Netherlands, with approval imminent in the UK, and has MRC approval in the EU. Working with the Australian lung physiologist, Dr Sandra Anderson, He developed the first successful bench-to-market inhalation aerosol product, wholly within Australia. The inhaled mannitol aerosol provides an important disease management to millions of asthma sufferers, and is particularly valuable as an objective assessment test for the early detection of asthma in young children. Click here for more details of Aridol Mannitol aerosols
Fundamental advances
Particle engineering for aerosol delivery. Professor Chan first developed particle engineering techniques to produce elongated particles to improve the aerodynamic behaviour of anti-asthmatic aerosol powders in collaboration with his doctoral supervisor, Dr I Gonda (now CEO of Aradigm Inc.) [10]. This work was awarded the Sigma Drug Delivery Prize in 1989. He has since reconceived those methods to produce corrugated particles for the same purpose, by substituting conventional crystallisation with precisely controlled techniques of spray drying. This resulted in opportunities for further improving the aerodynamic behaviour of other major drugs, in particular, protein-based compounds. He announced this innovation in a plenary lecture on the role of particle morphology in powder inhalers at the prestigious Respiratory Drug Delivery Conference in April 2007 in Paris.
Inhalers. Computational fluid dynamics (CFD) has been used widely by industry engineers in the modelling of fluid systems. Professor Chan's group uniquely applied CFD to develop a deep understanding of inhaler design and performance - previously understood only rudimentarily in terms of air turbulence and particle collisions. The work generated new information about air flow patterns inside an inhaler, data that were previously difficult to obtain experimentally [2]. It accurately delineated the role of a grid as an air flow retifier, which has expanded common definitions of it as simply a retainer of capsule fragments. It was shown that increasing turbulence by reducing the inhaler air-inlet dimension must coincide with teh release of powder into the air stream to enhance the inhaler performance. These concepts, developed over the past five years, have produced significant interest from the mjor pharmaceutical companies in the field.
Characterisation of the electrostatic properties of inhalation aerosols. Professor Chan’s group was the first to establish the use of an electrical low-pressure impactor (ELPI) for the simultaneous measurement of both the charge and aerodynamic size distributions of aerosol particles [1]. This technique is far superior to the conventional Faraday pail, which is limited to measuring only net charge measurement rather than the charge distribution in particle-size fractions. Using an ELPI, we revealed significant disparities between the charge profiles of commercial metered dose inhalers (MDIs). These findings have practical ramifications for the lung deposition of MDI aerosols, with potential benefits to the community through improved health outcomes and the more closely targeted regulation of generic aerosol products. The MDI paper [1] was quoted in the US publication Pharmacy Choice [http://www.pharmacychoice.com/News/article.cfm?Article_ID= 21392] to guide correct professional decision-making.
In-vivo characterisation of aerosol deposition in the lungs. In collaboration with the Australian nuclear physicist, Dr S Eberl, Professor Chan developed the single-photon emission computed tomography (SPECT) into a rapid, dynamic technique to investigate the 3D distribution of aerosol inhaled to the lungs [4]. His one-minute protocol eliminates the problem of aerosol clearance encountered in conventional SPECT, which previously required up to 30 minutes of imaging (thus delivering images of low accuracy). It has provided the first clear evidence of the differences in lung deposition from the hygroscopic growth of aerosols during transit in the airways. Professor Chan presented an invited plenary lecture on this work at the International Society of Aerosol in Medicine Conference 1999 and again in 2005 with new applications in dry powder aerosols. The rapid technique and the high-resolution 3D images that it produces, have streamlined research design in aerosol drug testing. Applying this innovative technique in a recent study, he has provided evidence on the precise effect of particle size on the lung deposition of polydisperse dry powder aerosols.
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Staff Profile
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