10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Directly Measuring the Rapid Evaporation/Growth of Metered Dose Inhaler/Dry Powder Inhaler/Nebulizer Formulations
ALLEN E. HADDRELL, David Lewis, Tanya Church, Jonathan P. Reid, University of Bristol
Abstract Number: 366 Working Group: Aerosols in Medicine
Abstract Targeted delivery of pharmaceuticals in the lung could result in less required total dose, lowering exposure time, prevalence of side effects and overall cost. A consensus forum of industrial, academic and regulatory experts identified a poor understanding of the relationships between physicochemical characteristics of drug formulations and performance in the humid environment of the respiratory tract as one key barrier to progress in inhalation therapeutics (a). Thus, quantifying the properties of pharmaceutical aerosol that govern hygroscopic growth will yield the potential for the rational design of new formulations for drug delivery to the lung. The ability to control the hygroscopic growth of inhaled pharmaceutical aerosol to improve drug efficacy through targeted dosing has received renewed interest in recent years.
Broadly speaking, the delivery of an active pharmaceutical ingredient (API) from a starting formulation to the deep lung involves three phases: aerosol generation, transport from the aerosolization device to the mouth, and concludes with inhalation/deposition. The deposition rate in the lung is controlled by the aerodynamic diameter of the droplet at the time of deposition. Thus, the size of the droplet at the point of generation, the reduction in droplet size resulting from the net loss of volatile mass (if present) during transfer from the device to the mouth, and any hygroscopic growth on inhalation will have a dramatic effect on total and regional dose. The interplay between these complex processes are explored here.
The novel aerosol analysis technique for measuring the hygroscopic properties of surrogates of ambient aerosol, the comparative kinetic electrodynamic balance (CK-EDB) was used in this study. Capabilities that are unique/advantageous to the CK-EDB include:
(1) Use of a water droplet to probe the RH of the airflow that the sample droplet is subsequently studied in with accuracy of ±0.1%, an order of magnitude better than conventional RH probes.
(2) Direct measurement of the dynamic behaviour of a droplet of known composition in a static and/or variable environment (resolutions of 50 nm and <100 milliseconds).
(3) Accurate determinations of the radial growth factor, a measure of the equilibrium hygroscopic growth of the aerosol as a function of gas phase RH across a range of RH from dry to >99%, and with temperature ranging from <50C to <-30C. samples.
To be presented are the kinetic and thermodynamic hygroscopic properties of commercially available nebulizer, DPI, and MDI formulations as measured by the CK-EDB.
(a) Forbes, B. et al., Adv. Drug Del. Rev. 2010, 63, 69–87.