We wanted to evaluate whether lung deposition of budesonide and terbutaline sulphate differs, and to determine lung deposition of budesonide inhaled at different peak inspiratory flows, through Turbuhaler. Lung deposition of budesonide, a lipophilic substance, and of terbutaline sulphate, a hydrophilic substance, was therefore compared, after administration via an inspiratory flow-driven, multi-dose, powder inhaler (Turbuhaler, Astra Draco AB) to 10 healthy volunteers. The radionuclide 99mTc was used to label drug particles, and radioactivity, indicating drug deposition, was measured using a gamma camera. Budesonide was inhaled at a normal flow of 58 l.min-1 and at a slow flow of 36 l-min-1. At the faster flow, a mean +/- SD 27.7 +/- 9.5% of the metered dose was deposited in the lung and at the slower flow 14.8 +/- 3.3% was deposited (p < 0.001). Mean lung deposition of terbutaline sulphate inhaled at 57 l.min-1 was 27.0 +/- 7.7%. We conclude that inspiratory flow has an important effect on lung deposition, but water solubility appears to have no effect.

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Methodological aspects of planar gamma scintigraphy used to quantify pulmonary aerosol deposition were investigated using an experimental dry powder formulation. Particles of micronized salbutamol sulphate were labelled with technetium-99m and admixed to an ordered mixture of unlabelled micronized salbutamol sulphate and larger carrier particles of lactose. The radioaerosol was administered to 24 healthy subjects, 12 in each of two consecutive, similarly designed studies. Pulmonary deposition was determined using two methods: repeated planar imaging, and pharmacokinetic assessments following charcoal co-administration to prevent gastrointestinal salbutamol absorption. After due consideration had been taken to ensure appropriate radiolabelling, image acquisition and processing procedures, a scintigraphic estimate of 26.2% (with 95% confidence interval of 24.2-28.4%) was obtained, which did not significantly differ from the pharmacokinetic estimate of 26.4% (24.4-28.7%). In summary, pre-study validation of the radiolabelling technique, quality control of radioaerosols produced during the study, correction for re-distribution of radiolabel from the lungs, selection of regions of interest, assessment of lung contours, correction for tissue attenuation of gamma rays and establishment of the actual recovery of radioactivity in the scintigraphic measurements could potentially affect the accuracy of the scintigraphic estimate of pulmonary deposition and, thus, should be carefully considered in the design or evaluation of any such study.