Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects.

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.

Nasal distribution of budesonide inhaled via a powder inhaler.

The distribution pattern of budesonide in the nasal passages and lungs was investigated in 10 healthy subjects after nasal inhalation. The subjects inhaled drug powder, radiolabelled with 99mTc, at maximum flow rate (46.3 +/- 6.8 l/min) and at 29.9 +/- 2.5 l/min via Turbuhaler. At both flows, the majority of the dose was deposited in the anterior part of the nasal cavity on a single, rather localized area, but some particles also penetrated more posteriorly into the main nasal passages and to the lungs. At maximum flow rate the nasal deposition was 65.2% (range 39.5-84.1%) and the lung deposition 4.7% (range 1.4-9.3%) of the metered dose, and at 30 l/min, the nasal deposition was 67.6% (range 49.7-81.6%) and the lung deposition was 4.2% (range 1.7-7.9%). A large fraction of the metered dose was deposited in the nasal adaptor of the inhaler during the administration (mean values 29 and 28%, for the two inhalation flows). Of the dose actually reaching the subject, 91 and 93% (mean values) was deposited in the nose. There were no statistically significant differences in distribution pattern between the two inhalation flows.

Deposition and clinical efficacy of terbutaline sulphate from Turbuhaler, a new multi-dose powder inhaler.

A radioaerosol technique has been developed in order to assess deposition patterns from a new metered dose powder inhaler (Turbuhaler, Astra Pharmaceuticals). The radionuclide Tc99m dissolved in chloroform was added to a spheronised formulation of micronised terbutaline sulphate and the chloroform was allowed to evaporate. Turbuhaler subsequently delivered 0.5 mg of treated drug per metered dose. In vitro tests with a multistage liquid impinger showed that the fractionation of the drug dose between different particle size bands was similar to the fractionation of radioactivity. In a group of ten asthmatic patients, a mean 14.2% (SEM 2.1) of the drug dose was deposited in the lungs, with 71.6% (3.0) of the dose in the oropharynx. Of the remainder, 13.7% (2.1) was deposited on the mouthpiece, and 0.5% (0.2) recovered from exhaled air. The radiolabel was present in both central and peripheral zones of the lungs. All patients bronchodilated; forced expiratory volume in one second (FEV1) increased from 1.40 (0.24) l to 1.77 (0.24) l (p less than 0.01) 20 min after inhalation. These results suggest that both the distribution of drug and the clinical effect of terbutaline sulphate delivered from Turbuhaler are similar to those from a pressurised metered dose inhaler (MDI).