An In Vitro Dissolution Method for Inhaled Drugs Depositing in the Tracheobronchial Lung Region.

Abstract

Purpose: To evaluate and develop a novel dissolution test method using tracheobronchial (TB) mimic filters for assessing the dissolution behavior of inhaled drugs targeting the tracheobronchial lung region.

Methods: Fluticasone propionate (FP), a poorly soluble corticosteroid, was selected as the test drug. A novel filter-based apparatus (FBA) fractionated the inhaled dose into extrathoracic, tracheobronchial, and alveolar fractions. FP was delivered via dry powder inhaler (DPI) (Flovent Diskus, 250 µg) and pressurized metered-dose inhaler (pMDI) (Flovent HFA, 250 µg). Regional deposition estimates were compared between inhalers. Dissolution tests were performed on the captured TB dose using phosphate-buffered saline + 0.5% sodium dodecyl sulfate at 37 °C. First-order dissolution rate constants ( $k_1$ ), difference ( $f_1$ ), and similarity ( $f_2$ ) factors were calculated. Particle distribution and loading effects on the TB filter were assessed using scanning electron microscopy (SEM).

Results: The TB filter demonstrated consistent performance, with no drug loading effects observed for up to the highest drug loading tested, which was 7 actuations of the DPI (~ 110 µg FP collected on the TB filter), or 5 actuations of the pMDI (~ 170 µg). Dissolution profiles revealed no significant differences across DPI doses, and slower dissolution rates for the pMDI compared to the DPI, with $k_1$ values indicating significant differences (p < 0.05). SEM showed no particle aggregation or filter clogging. Similarity and difference factors supported these findings.

Conclusions: The dissolution method discriminated between the two inhalers and is a promising new tool for use in the dissolution testing of orally inhaled drug products.