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

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.