, Volume 27, Issue 5, pp 786-795
Date: 13 Mar 2010

In Vitro Aqueous Fluid-Capacity-Limited Dissolution Testing of Respirable Aerosol Drug Particles Generated from Inhaler Products

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Abstract

Purpose

To develop a unique in vitro aqueous fluid-capacity-limited dissolution system for the kinetic assessment of respirable aerosol drug particles from inhaler products.

Methods

Aerosol particles of 5 inhaled corticosteroids (ICSs) from 7 inhaler products were collected in the aerodynamic 2.1–3.3 or 4.7–5.8 μm on the filter membranes using the Andersen cascade impactor. Each filter membrane was then placed onto the donor compartment of the Transwell® system, where addition of 0.04ml aqueous fluid initiated aerosol ICS dissolution and permeation across its supporting membrane at 37°C and ∼100% humidity.

Results

The % profiles of dissolution and permeation were apparent first-order or pseudo-zero-order, reaching varying 1.9–95.0% by 5 h. Their kinetics overall conformed to the ICS aqueous solubility. With increasing aerosol mass, however, the profiles decelerated, attributed to undissolved ICSs left by the limited dissolution fluid capacity. The profiles could be also product-specific, as beclomethasone dipropionate aerosols from QVAR® dissolved faster than those from VANCERIL®, whereas fluticasone propionate aerosols from two different inhaler products exhibited comparable profiles. The 2.1–3.3 μm aerosols dissolved faster than the 4.7–5.8 μm aerosols.

Conclusions

Aerosol ICS dissolution into the limited aqueous fluid volume differed kinetically due to ICS solubility and aerosol mass, size, formulation and/or generation.