Optimization of Coventional pMDIs for a Better Salutamol Delivery System
Luu, Ha (Natalie); Lin, Kimberly; Contreras, Danya; Curley, Stephanie
The most commonly prescribed method of treatment for asthma today is the pressurized metered dose inhaler (pMDI). However, many patients fail to use it correctly, resulting in the inefficient administration of the drug. There are two main methods to maximize the efficacy of an inhaler: 1) increasing the concentration of the drug per dose; and 2) optimizing drug particle deposition in the lungs by minimizing deposition in the upper airway. Previous studies have shown that doubling the inhaled dose is minimally effective, and it also increases the risk of experiencing side effects. Thus, minimizing particle deposition in the upper airway is the more viable approach. Computational fluid dynamics (CFD) modeling is necessary for determining the ideal parameters that will minimize the drug loss during species transfer and maximize the drug’s effectiveness. The goal of this study is to develop a model that simulates the particle trajectory and deposition of salbutamol, an anti-asthma drug (Drug Information Online, 2013), through the oral cavity and laryngeal-trachea regions of the upper respiratory tract. Besides modeling the system, topics of optimal flow rate, initial velocity of drug particles at the mouth inlet, and aerosol drug size are also discussed. The COMSOL Multiphysics 4.3 simulation software was used to solve the governing equations employed in our simulation. Turbulent fluid flow from inhalation was modeled with 2-dimensional Navier Stokes fluid flow equations, and the Lagrangian Particle Tracking method was used to describe the distribution of the drug. Fraction of particle deposition in the upper airway tract was determined for a range of breathing flow rates, inlet particle velocities, insertion angles, and particle sizes to find optimal values. Deposition of salbutamol at different inhaler insertion angles was also measured. Results showed that particle deposition is minimized with particle diameters of 1-10µm and flow rates of 30-60 L/min. A subtle dependence on particle velocity was noted for particles of 10-20µm in size; there was a small increase in deposition as particle velocity increased for a given flow rate and particle size. For a particle diameter of 30µm, as much as 100% of all particles deposited in the upper airway tract for the higher flow rates of 50, 60, and 75 L/min. For particles that were <10µm, the percentage of particles that deposited in the respiratory tract did not change appreciably with changing particle inlet velocity across all flow rates tested, consistently showing ~3.5% particle deposition. For medium-sized particles that were between 10µm and 30µm in diameter, the amount of drug reaching the lungs can be maximized by choosing a lower flow rate, <50 L/min, and lower spray velocity, <7.3 m/s. For salbutamol in particular, the amount of deposition at different spray cone angles did not show a significant trend. The implications of our findings will lead future designs of pMDI to focus on obtaining the optimal combination of parameters for drug size, breathing flow rate, and particle inlet velocity. Our observations on the dependence of particle deposition on drug size will allow extending the application of our model to other drugs of different sizes and potentially lead to modifying inhalers accordingly. For future studies, our analysis can be extended to consider the deposition location for the same range of flow rates, spray velocities, and drug sizes, and spray cone angle. In addition, the effect of different mouth geometries on deposition location can be explored.
inhaler; salbutamol; pMDI; particle deposition; asthma