Mechanisms of Pharmaceutical Aerosol Deposition in the Respiratory Tract

Abstract

Abstract. Aerosol delivery is noninvasive and is effective in much lower doses than required for oral administration. Currently, there are several types of therapeutic aerosol delivery systems, including the pressurized metered-dose inhaler, the dry powder inhaler, the medical nebulizer, the solution mist inhaler, and the nasal sprays. Both oral and nasal inhalation routes are used for the delivery of therapeutic aerosols. Following inhalation therapy, only a fraction of the dose reaches the expected target area. Knowledge of the amount of drug actually deposited is essential in designing the delivery system or devices to optimize the delivery efficiency to the targeted region of the respiratory tract. Aerosol deposition mechanisms in the human respiratory tract have been well studied. Prediction of pharmaceutical aerosol deposition using established lung deposition models has limited success primarily because they underestimated oropharyngeal deposition. Recent studies of oropharyngeal deposition of several drug delivery systems identify other factors associated with the delivery system that dominates the transport and deposition of the oropharyngeal region. Computational fluid dynamic simulation of the aerosol transport and deposition in the respiratory tract has provided important insight into these processes. Investigation of nasal spray deposition mechanisms is also discussed.

Delivery of ALX-0171 by inhalation greatly reduces respiratory syncytial virus disease in newborn lambs

“…Such deposition is strongly affected by: 1) breathing patterns (respiratory frequency and breathing volume), which is dependent on body size; 2) airway anatomy/geometry as function of gender, age and disease status; and 3) by the aerosol aerodynamic diameter, which is dependent on the administration device characteristics. 20-22 For small animal species such as rodents, direct instillation of drug to the lungs is the principal lung-dosing method, which offers the advantage of enabling accurate dosing. However, this method can result in substantial variations in lung-regional deposition as well as variations in systemic drug profiles 28 .…”

“…Other important parameters that affect drug deposition is the breathing maneuver and the aerosol aerodynamic diameter. 20-22 Lambs breath through the nasal meatus, although oral inhalation is possible when the nasal airways are obstructed, which is also the case for human infants 23 . For the reasons stated above, the neonatal lamb model was selected for the evaluation of ALX-0171 efficacy and safety in a neonatal setting.…”

Comparison of Aerosol Delivery by Face Mask and Tracheostomy Collar

“…Airway models have been developed as a surrogate for studying aerosol deposition in the human airway. 5,6 Breathing pattern is known to have a significant effect on aerosol deposition. In a combined human/laboratory model, Brand et al 7 reported that subjects breathing via a mouthpiece at a very slow flow had significantly greater deposition than at higher flows, although inter-and intra-subject flows varied by as much as 22%.…”

Engineered Aerosol Medicine and Drug Delivery Methods for Optimal Respiratory Therapy

“…[3][4][5][6][7][8][9] In silico study results using these modeling tools agreed with in vitro study results as well. 10,11 In the field of aerosol medicine, there have been several methods invented and marketed to improve pharmacokinetic efficacy and effectiveness in respiratory drug delivery, and to minimize losses in the delivery devices. Examples are: nanoparticle therapeutics for reduced side effects and more targeted deposition, salt-based formulations optimized for inhalation to create a robust and flexible platform that can accommodate low or high drug loads of a range of molecule types, sustainable long pulmonary absorption achieved through tissue binding and cellular uptake in the airways, moderately lipophilic compounds with positive electrostatic charge under physiological conditions to bind preferentially lung tissues, liposomal encapsulation in controlled-release particles, and increasing the molecular mass of the drug by conjugation with a water-soluble inert ligand or another protein.…”