The Demonstration of Bronchodilator Effects of Salbutamol Formulated in Chlorofluorocarbon and Hydrofluoroalkane-134a Metered Dose Inhalation Devices on Leukotriene D₄-Induced Pulmonary Responses in the Guinea Pig

Abstract

The demonstration of bronchodilator effects of ß2-adrenergic agonists delivered by metered dose inhalation (MDI) devices can be useful in the development of new therapies for asthma or assessing the effects of a formulation. MDI formulations of hydroiluoroalkanc (HFA)-134a (a chlorofluorocarbon [CFC]-free propellant), salbutamol in the HFA-134a propellant, CFC-P11/P12 propellant, and salbutamol and formoterol in the CFC propellant were evaluated for their ability to reduce leukotriene D4 (LTD4)-induced bronchoconstriction in guinea pigs using the Konzett-Rossler method. LTD4 challenges were made at various times up to 6 hours after MDI treatment. Neither the placebo vehicle propellants nor the drug formulations affected basal airflow. Only the salbutamol/CFC, formoterol/CFC, and salbutamol/HFA MDI formulations inhibited LTD4-induced bronchoconstriction. One actuation of the MDI device containing salbutamol or formoterol in the CFC propellant produced -100% inhibition of LTD4-induced effects following a 5-minute pretreatment period at doses greater than or equal to 10 pg per actuation. A single actuation of salbutamol (100 fig per actuation) was required to show significant inhibition 30 minutes after aerosol drug delivery (-50% inhibition) and was inactive 1 hour after drug delivery. Inhibition with formoterol was observed at 30 minutes after aerosol delivery at 25 fig per actuation and for up to 6 hours at 100 fig per actuation. Results 41 HAMMERBECK ET AL.of this study indicate that the bronchodilator activity of MDI-delivered /^-adrenergic agonists could be demonstrated using either CFC or HFA propellants in a standard preclinical animal model.

Inhalation System for Pulmonary Aerosol Drug Delivery in Rodents Using Large Porous Particles

“…Although local treatment of the respiratory airways with drug aerosols has been known since the end of the last century, it has only been in recent years that pulmonary drug delivery for systemic therapy has become especially attractive as demonstrate d by the recent rise in the number of recent investi-( gations Patton and Platz 1992;Niven 1993; ) Wall 1995;Hammerbeck et al 1997 . The tremendous scienti® c and biomedical interest in inhalation therapies is justi® ed by the number of advantage s that the pulmonary route offers for both the local and systemic delivery of therapeutics.…”