Deposition and Pharmacokinetics of an HFA Formulation of Triamcinolone Acetonide Delivered by Pressurized Metered Dose Inhaler

Novel formulations of asthma drugs contained in pressurized metered dose inhalers (pMDIs) are being developed containing hydrofluoroalkane (HFA) propellants. The objectives of this study were to assess the deposition in the lungs and oropharynx of triamcinolone acetonide (TAA; Azmacort^®, Aventis Pharma, Collegeville, PA) delivered by pMDI formulated with HFA-134a, together with the pharmacokinetic profile of TAA, and to determine the extent to which the Azmacort^® spacer improves targeting of TAA to the lungs. The deposition of TAA, labelled with ^99mTc, was assessed by gamma scintigraphy in 10 patients with mild to moderate asthma (mean forced expiratory volume in one second [FEV1] 76% predicted), who received in randomized order three delivered (ex-device) doses of 75 μg TAA via pMDI coupled to an Azmacort^® spacer (TAA - spacer), and three delivered doses of 230 μg TAA via the same device, but with the spacer removed (TAA - no spacer). Mean lung deposition expressed as mass of drug was similar for each regimen (TAA - no spacer 175 μg; TAA - spacer 188 μg), but when expressed as percentage delivered dose, lung deposition was higher for TAA - spacer (53.8%) versus TAA - no spacer (26.0%), indicating superior drug targeting for TAA - spacer. The spacer reduced oropharyngeal deposition. The pharmacokinetic data showed higher plasma levels of drug for TAA - no spacer, resulting from higher oropharyngeal deposition. "Pharmacoscintigraphic" data showed proof of concept for a novel HFA delivery system for an inhaled corticosteroid based on pulmonary targeting of drug.