ARLA

the Aerosol Research Lab of Alberta

Past Research

Much of the research performed to date by the Aerosol Research Laboratory of Alberta (ARLA) is presented in publications available in the archival literature. A brief summary of some of this research is given below.

Part of the work done at ARLA has focused on developing ways to control and predict how much drug deposits in the different parts of the respiratory tract with inhaled pharmaceutical aerosols (IPAs), much of which is incorporated in our Deposition Calculator that allows on-line calculation of respiratory deposition for a variety of relevant parameter values. Recent work by ARLA using many replicas of the mouth, throat and nose airways in subjects across the age spectrum has provided a detailed fundamental understanding of mouth-throat deposition with inhalers, allowing improvements in our ability to precisely deliver drugs to the lungs in infants, children and adults. Such methods are useful in helping design and evaluate IPA devices. Indeed, the "Alberta Idealized Throat" geometry developed by us is used worldwide to evaluate mouth-throat deposition of IPAs. Its companion idealized child mouth-throat geometry and idealized infant nasal geometry allow benchtop measurements of aerosol delivery over the complete range of ages from infant to adult. Recent models developed at ARLA also allow prediction of drug concentrations in the airway surface fluid, now routinely used at ARLA to aid in developing formulations and delivery systems for drugs intended for local activity in the airways (such as antimicrobials and mucolytics, an example of which is shown in Figure 1).

ASL concentration predictions
Figure 1. Model predictions of the concentration in the airway surface liquid (ASL) of different lung generations for a novel liposomal cationic peptide (CM3) after aerosol delivery by nebulization are shown for adult, 8 yr. old and 4 yr. old child model lungs. ©ARLA

ARLA has been instrumental in the development of models that allow prediction of evaporation and condensation of IPAs in the moist environment of the lung in which the presence of the particles affects the humidity in the lung and vice versa (so-called two-way coupled hygroscopic models, an example of which is shown in Figure 2).

Eulerian simulation
Figure 2. The number of droplets of different diameter (in micrometers) is shown as an evaporating aerosol travels a distance x (in cm) in a simulation of two-way coupled hygroscopic behaviour. ©ARLA

An important part of this work involves validating these models by performing studies to compare to experimental measurements of IPA deposition in human subjects. A three-dimensional radionucleotide image of the lungs of a patient from one such study at ARLA is shown in Figure 3.

3D radionucleotide image
Figure 3. 3D radionucleotide image. ©ARLA

Another part of the research done at ARLA has focused on developing and evaluating delivery systems for various new and existing drugs (an example of one such formulation is shown in Figure 4 below).

Much of this work is proprietary, since it involves new technology and formulations that remain undisclosed. However, ARLA has been instrumental in developing various novel experimental methods that allow more realistic characterization of IPAs during simulated human breathing, allowing exploration and understanding of several factors not previously understood, such as the negative effect of humidity on spacers used with ventilated patients, and the effect of nebulizer cooling on droplet undersizing in cascade impactors.

SEM formulation
Figure 4. A scanning electron microscope of the particles in a novel interactive liposome powder developed at ARLA. ©ARLA
These novel methods have been used at ARLA for inertial sizing during realistic breath simulation to explore the effect of breath simulation on measurements of aerosols from dry powder inhalers, add-on devices with pressurized metered dose inhalers, as well as nebulizers. In addition, by combining such measurements with our models of aerosol behaviour in the respiratory tract, we are able to optimize and evaluate drug formulations and delivery systems prior to beginning human or animal studies. Indeed, we have collaborated with many companies and agencies, using our methods to help optimize IPA systems prior to in vivo studies. This work includes extension of these methods to consider aerosols consisting of suspensions (rather than solutions), including liposomes and their associated tendency for disruption. In addition, we have used this approach to allow comparison of many different delivery devices already on the market.

Despite the continuing efforts of ARLA and many other laboratories around the world, much about IPAs remains poorly understood, partly due to the complexity of their behaviour. ARLA is part of a strong worldwide community of researchers dedicated to improving our understanding and ability to predict the behaviour of inhaled pharmaceutical aerosols.