Large porous particles for sustained protection from carbachol-induced bronchoconstriction in guinea pigs

Purpose. To determine whether a new formulated albuterol aerosol could sust ain inhibition to bronchoconstriction for approximately one day in guinea p igs challenged with carbachol. Methods. Large and porous particles, comprising a combination of endogenous or FDA-approved excipients and albuterol sulfate, were prepared by spray d rying using a NIRO portable spray drier. The anesthetized animals inhaled 5 mg of large porous or small nonporous particles by forced ventilation via cannulae inserted in the lumen of their exposed tracheae. At regular interv als over a period of 36 hours after drug delivery, airway resistance was de termined in response to carbachol challenge dose. Results. Whereas inhalation of small nonporous albuterol particles protecte d from the carbachol-induced bronchoconstriction for up to 5 hours, inhalat ion of large porous albuterol particles produced a significant inhibition o f carbachol-induced bronchoconstriction for at least 16 hours. Conclusions. The absence of substantial side effects, verified over a perio d of 24 hours by evaluating cardio-respiratory parameters as well as pulmon ary inflammation, supports the utility of large porous albuterol particles for sustained therapies in asthma and other types of lung disease.