A Human Oral-throat Cast Integrated with a Twin-stage Impinger for Evaluation of Dry Powder Inhalers

Abstract

The aim of this study was to investigate the applicability of replacing the glass throat from a twin-stage impinger (TSI) with a human oral-throat cast. Monodisperse aerosols were used to calibrate the human oral cast-TSI at 60 L min(-1) and cut-off in particle size was compared with that of the TSI described in the British Pharmacopoeia which employs a glass throat. The amount of salbutamol sulphate (and lactose) delivered by the Cyclohaler depositing on various elements of the in-vitro model were determined. The calibration of the model containing a human oral-throat cast at 60 L min(-1) gave a particle size cut-off of 5.2 microm which was less than that of the TSI (6.3 microm). The oral-throat cast trapped more drug than the glass throat model with a formulation that employed the larger carrier (63-90 microm; P<0.05) while it trapped a lesser amount of drug with those filled with the lower size carrier (Lactochem, micronised lactose). The greater amount of lactose in the formulation that employed the larger-sized carrier (63-90 microm) was deposited closer to the inlet of the oral-throat cast than to the inlet of the glass throat model. Replacement of the glass throat in the TSI by the human oral-throat cast, leads to a change in deposition efficiency, with the cast having a higher filter efficiency and hence more aerosol particles being captured before their entry into the TSI. This should be investigated further to determine whether such a model might provide a more realistic assessment of the in-vivo characteristics of an aerosol in comparison with the TSI currently being employed, which utilises the glass throat as the portal of entry.

Development of the Premature Infant Nose Throat-Model (PrINT-Model)—An Upper Airway Replica of a Premature Neonate for the Study of Aerosol Delivery

“…Several human upper airway casts have been developed to study aerosol deposition (7,8) from infancy to adulthood. Both mathematical and anatomical models have been developed for adults (9 -12).…”

Aerosol Drug Delivery to the Lungs

“…Of these, the USP -1, USP -2, and twin impinger inlet have been the most popular [87] . Unfortunately, these inlets do not accurately represent the complex geometry of the mouth and throat, and are known to underpredict mouth -throat deposition [88,89] . Replicas based on casts or images of individual mouth -throat geometries are more realistic, but their lack of generality, especially considering the large intersubject variability in mouth -throat deposition, is problematic.…”

Inhaled Pulmonary Drug Delivery Platform Using Surface Acoustic Wave Atomization

“…As shown in Fig. 2, "A" and "B" represent the oral area and trachea respectively, while the bottom glass, "C" (from "C1" to "C2"), is the area that simulates the targeted lung [27][28][29]. As albuterol and octanol are immiscible with water, 7 ml and 30 ml of ethanol, instead of water being proposed in [27], were placed in "B" and "C" respectively to model the lung humidity.…”