The output of budesonide from spacer devices assessed under simulated breathing conditions.
BACKGROUND: Spacer devices are increasingly used to aid inhalational therapy, and many different devices are available. Patient and spacer size and spacer static charge may affect drug delivery, but the optimum spacer size and method of reducing static charge is not certain. OBJECTIVE: We sought to determine the output of budesonide from 3 different spacer devices when assessed by using simulated breathing at different tidal volumes and to assess the effect of washing and handling the spacer on drug output. METHODS: Three spacer types were assessed: 2 polycarbonate spacers, the Aerochamber and the Nebuhaler, and the metal Nebuchamber or Non-Electrostatic-Spacer. Breathing was simulated by using a sinus flow pump. Metered-dose inhalers of budesonide 200 microg were actuated into the spacer, which was attached to the breathing simulator for 5 simulated breathing cycles. Budesonide was collected on a filter placed between the spacer and breathing simulator and was assayed by HPLC. Spacers were assessed after they had been washed briefly in water, after they had been washed briefly in cetrimide solution in an attempt to reduce their static charge, and after they had been handled to simulate normal use. In separate experiments budesonide particle size from the spacers was measured by using a multistage liquid impinger. RESULTS: Drug output from the Nebuchamber was greater than that from the other 2 spacers, especially at lower tidal volumes. With 150 mL of tidal volume, the Nebuchamber delivered 36% of the nominal dose to the filter versus 13% from the Nebuhaler and 7% from the Aerochamber. The output from the Aerochamber and Nebuhaler increased linearly with tidal volume, but this was not the case with the Nebuchamber, in which output was constant at tidal volumes of 150 mL and above. Compared with washing in tap water, neither washing the spacers in 0.1% cetrimide solution nor vigorous wiping with a paper towel changed their output. Thirty-eight percent of the drug from the Nebuchamber was contained in particles smaller than 4.7 microm in diameter compared with 47% from the Nebuhaler and 53% from the Aerochamber. CONCLUSIONS: The Nebuchamber increases in vitro budesonide delivery compared with the polycarbonate spacers tested but delivers a greater percentage of the drug in large particles. No increase in delivery with tidal volume was seen with the Nebuchamber, which would deliver a higher dose of drug per kilogram of body weight to smaller patients. Briefly washing the polycarbonate spacers in water or in a weak detergent solution, simulating household washing, did not make them as effective as the metal spacer. Further research is needed to determine a practical washing and handling method to reduce static charge on polycarbonate spacers.