Mechanisms of pharmaceutical aerosol deposition in the respiratory tract

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.

Fig. 1

A schematic diagram of the human respiratory tract

Fig. 2

Distribution of particle deposition for different regions of the respiratory tract system for 100% nasal breathing. The data were calculated using the LUDEP software (NRPB, Oxon, UK) based on the ICRP model (6)

Fig. 3

Distribution of particle deposition for different regions of the respiratory tract system for 100% mouth breathing. The data were calculated using the LUDEP software (NRPB, Oxon, UK) based on the ICRP model (6)

Fig. 4

Correlation of lung deposition with the fine particle fraction (32). MDI = metered-dose inhaler; DPI = dry powder inhaler; SMI = soft mist inhaler

Fig. 5

Oral deposition efficiency in a human airway replica as a function of the impaction parameter and flow rate (20). The solid curve is the best-fitted curve

Fig. 6

Comparison of oral deposition in the replica with reported in vivo deposition data. The solid curve is the best-fitted curve for the in vivo data, and the dashed curves are fitted curves with ±SD (with permission from Cheng et al. 20)

Fig. 7

Velocity profiles in the oral airway model at Q = 15 L min⁻¹. The left panel exhibits midplane (y = 0 plane) velocity contours with uniform velocity vectors. The right panel shows the axial velocity contours (magnitudes in centimeters per second) and secondary velocity vectors at different cross sections (with permission from Kleinstreuer and Zhang (51)

Fig. 8

Midplane flow field results for inlet diameter, Din = 3.0 mm, and inhalation flow rate, Q = 32.2 L min⁻¹, of dry powder aerosol delivery in an oral airway (with permission from Matida et al. (56)

Fig. 9

Schematic of a human adult nasal airway

Fig. 10

The human multi-sectional nasal airway model

Fig. 11

Deposition pattern in the anterior, turbinate, and posterior regions of the nasal airway (with permission from Cheng et al. (64))

Fig. 12

Composite plot of turbinate deposition versus plume angle with different administration angles. Curves are provided for visualization only. No functional dependence is implied (with permission from Foo et al. (65))