Drug inhalation is quickly emerging in the field of drug delivery techniques, providing localized treatment for various types of lung disorders. To expand oral drug delivery, this project will focus on inhaled insulin therapy to provide a systemic treatment that will reduce the detrimental effects of diabetes. Previous research has shown that inhaled insulin is more efficient and preferable to patients compared to the commonly used insulin injection therapy. However, there are several problems associated with drug inhalation techniques, including the impaction of drug against the natural right angle geometry of the pharynx, which results in decreased deposition in the lungs. The goals of this project include the optimization of insulin drug particle diameter size, the optimization of particle density, and optimization of the peak inhalation rate of drug to reduce impaction against the pharynx and to maximize deposition in the lungs.
Optimization of the aerosol insulin was done using a laminar flow COMSOL model. To simplify the model, a two dimensional, cross-section of the mouth and trachea was used as the biological system to measure the effectiveness of the delivery scheme. This model was used to test particles with density values ranging from 10 g/m3 to 800 g/m3, as well as particles with diameters ranging from 1 μm to 17.5 μm. In addition, particles were tested with peak inhalation rates ranging from 15 L/min to 90 L/min and inhaler insertion angles ranging from -10° to 10°. Using every permutation of particle density, particle diameter, peak inhalation rate, and insertion angle we sought to find the most optimal delivery system for deposition at the bottom of the trachea. Particle deposition was further analyzed by varying inhalation rate and particle parameters in a 2D turbulent flow model and a 3D laminar flow model. For the 2D laminar flow model, particle deposition was found to be the most sensitive to inhalation rate compared to the other experimental parameters. Results indicated that high inhalation rates (45-60 L/min), particles with low density (100-400 kg/m3) and low diameter (1-7.5 μm) resulted in increased particle deposition, which agrees with literature. For the velocity profile we obtained, the peak normalized velocity values of 1.53 for the 15 L/min inhalation rate, 1.37 for the 30 L/min inhalation rate, and 1.27 for the 90 L/min inhalation rate agree with the values recorded in literature. For the 2D turbulent flow model, varying inhalation rate, particle density and diameter appeared to have no significant effect on particle deposition. The turbulent model displayed particle depositions that were an order of magnitude lower than those of the 2D laminar model, which we believe to be due to turbulent dispersion effects. For the 3D laminar flow model, flow velocity did not vary in the z direction, which implies that the 2D laminar model is an appropriate representation of flow velocity Our model demonstrates the effects of changing various drug particle parameters on particle deposition. We recommend the use of particles with low density and low diameter along with high inhalation rates in order to reduce impaction in the oral cavity and increase deposition in the lungs. Since particle deposition was most sensitive to inhalation rate, when formulating oral drug treatment particles, the specific inhalation rate that is used should be carefully considered.