AEROSOL DEPOSITION AND CLEARANCE

Aerosol Deposition and Clearance from the Human Nasal Passage



Aerosol Deposition and Clearance from the Human Nasal Passage

Introduction

The Task Group of Cornrmttee 2 of the International Commission on Radiological Protection (ICRP) that developed the Human Respiratory Tract Model for Radiological Protection (HRTM) noted that data on the clearance of inhaled particles from the human nasal passage was limited and that further knowledge was desirable (ICRP, 1994). Therefore, nasal deposition and clearance by particle transport in human subjects has been studied to improve knowledge of these processes. Experiments for a range of particle sizes and work rates have measured nasal clearance over a much longer period than previous studies. The principal objective is to improve the accuracy and reliability of dose assessments of intakes by nasal inhalation (Suzuki Y, Makino Y, 1999).

In the HRTM the extra-thoracic compartment (ET) is divided into two sub-compartments, ET1 and ET2, which receive approximately equal deposits of inhaled aerosols. ET1 represents the skin-lined front of the nasal passage and has lower radiosensitivity than the rest of ET (ET2). The HRTM models all clearance from ET1 as nose blowing. The ciliated posterior nasal passage is part of ET2, from which clearance is modelled as mucociliary action to the gastrointestinal (GI) tract, except for 0.05°% that is sequestrated into airway walls and slowly clears to the ET lymph nodes (LNET). The ET1 and ET2 clearance rates are 1 and 100 per day, respectively. Nasal clearance in the HRTM is deliberately simplified by not including clearance from ET1 to ET2, but the ET1 and ET2 deposition fractions have been adjusted to compensate for this simplification.

The findings of the study were used to construct the Smith Etherington ET (S-E ET) clearance model, which aims to represent nasal clearance more realistically. This model has been used to assess doses received from ET deposition after nasal inhalation for comparison with HRTM predictions (Van de Donk HJM, Muller Plantema IP, Zuidema J, Merkus FWHM. 1980).

Literature Review

The nose is a complex organ from a kinetic point of view because three different processes: deposition, clearance or translocation and absorption of drugs take place inside the nose. For effective administration of therapeutic drugs through the nasal route, its anatomy and related physiological features must be taken into consideration. The nasal septum divides the nasal cavity into two unequal cavities. The septum consists mostly of cartilage and skin, and therefore, the penetration of drugs is low. The most efficient area for drug absorption is the highly vascularized lateral wall of the nasal cavity: the mucosa lined over the turbinates or conchae (Suzuki Y, Makino Y, 1999).

Effect of Deposition on Absorption

Deposition of the formulation in the anterior portion of the nose provides a longer nasal residence time. However, the anterior portion of the nose is an area of low permeability. On the other hand, depositing a drug in the posterior portion of the nose, where the drug permeability is generally higher, provides shorter residence time. The method of administration and properties of the formulation ...