In vitro and in vivo techniques used in drug development for evaluation ofdose delivery of inhaled corticosteroids

Oral inhaled corticosteroids are important in the treatment of asthma since their delivery is targeted directly to the lung, which is the site of acti on. Triamcinolone acetonide (TAA) is an effective and safe corticosteroid t hat is marketed as a metered-dose inhaler (MDI) with an integrated spacer ( Azmacort(R)) for the treatment of asthma. Due to the phasing out of chlorof luorocarbon (CFC) propellants, Azmacort(R) has been reformulated with a non -CFC propellant. Due to the complexities of oral inhaled formulations and t he topical nature of drug delivery to the lung for efficacy, the reformulat ion of oral inhaled MDIs requires careful consideration and support through out their development using a combination of in vitro and in vivo studies t o ensure clinical comparability for both efficacy and safety. This paper de scribes a chronological series of studies designed to support the reformula tion of Azmacort(R). These included in vitro studies to estimate respirable fraction, in vivo pulmonary deposition studies, in vivo pharmacokinetic-ph armacodynamic studies to estimate the systemic effects of each formulation, and final clinical studies in adult and pediatric patients to confirm the clinical comparability of the new formulation of Azmacort(R). The results o f these studies, performed at various stages during the development of new formulations, were critical in guiding the reformulation efforts for Azmaco rt(R). Journal of Clinical Pharmacology, 2001;42:7-18 (C) 2001 the American College of Clinical Pharmacology.