Comparison of TSI/Transwell® and NGI/Rotating Paddle as dissolution methods for orally inhaled products
Mireille Hassoun1, Mark Copley2, Paul G. Royall1, Mark Parry3, Ben Forbes1
1Institute of Pharmaceutical Science, King’s College London, SE1 9NH, UK
2Copley Scientific Limited, Colwick, Nottingham, NG4 2JY, UK
3Intertek-Melbourn Scientific Limited, Saxon Way, Melbourn, SG8 6DN, UK
The study compared prototype dissolution systems for inhaled products by investigating the dissolution of FP, delivered by 10 actuations of Flixotide® 50 µg Evohaler. Using a Transwell system, the inhaler was actuated into a Twin Stage Impinger (TSI), airflow 60 L/min, and the aerosol collected on an original Transwell insert (0.45 µm pore polyester membrane) or a Transwell in which the membrane was replaced by a GF/A glass microfibre filter. Using a rotating paddle system, the inhaler was actuated at air flow 48 L/min into a Next Generation Impactor (NGI) with a ‘Flow Access’ lid and the aerosol was collected on a glass microfibre filter paper after stage 2. Dissolution was evaluated using medium composed of 25-90% v/v methanol: water or 0.5% SDS in water. Greater aerosol mass was deposited in the NGI, 190-230 µg, compared to the TSI, 3-10 µg. The Transwell systems both showed slow and incomplete dissolution of FP in the medium over 60 min, whereas the rotating paddle method allowed more complete dissolution, approaching 100% of the deposited mass, and distinctly different dissolution profiles in the different media. As expected, the dissolution rate of FP increased as the proportion of methanol increased in the medium, in accordance with the solubilising capacity of methanol for the hydrophobic drug; the surfactant affected the dissolution of FP similarly. Further work is required to compare the advantages and limitations of these methodologies for measuring the effect of formulation factors on aerosol dissolution.