The inhalation rate is important when patients use an inhaler. Dry powder inhalers (DPIs) require an inhalation rate >30 L min(-1) whereas metered dose inhalers (MDIs) should be used at <90 L min(-1). Within the setting of a routine clinic, we have measured peak inhalation flows (PIF) of COPD patients when they used a Diskus (SDSK), Turbuhaler (STBH), Handihaler (SHAND) and MDI. Subjects were then randomised into trained (VT) and non-trained (NT) groups. One hundred and sixty-three patients with a mean (S.D.) age and % predicted FEV(1) of 72.5 (9.9) years and 47.8 (22.2)% completed the study. Of the patients, 4.9%, 14.2% and 57.0% inhaled <30 L min(-1) through SDSK, STHB and SHAND, respectively and 59.5% inhaled >90 L min(-1) with the MDI. Generally, the more severe the COPD, the slower was their PIF with all inhalers. The MDI PIF values in the VT group (n=84) post-training were significantly (p<0.001) slower but there was no change for the DPIs. Of the 55 VT patients inhaling >90 L min(-1) through the MDI only 7 (p<0.001) inhaled too fast post-training. Pre-training 3, 15 and 46 VT subjects inhaled <30 L min(-1) through the SDSK, STBH and SHAND and after training none, 5 and 26 did not inhale faster than this minimum required rate. Some COPD patients have problems achieving required PIFs through DPIs but training is useful to help some exceed the minimum required rate despite only small improvements. The patients found it easier to slow their PIF through the MDI.

Previously, dose emission below 30 L min(-1) through DPI has not been routinely determined. However, during routine use some patients do not achieve 30 L min(-1) inhalation flows. Hence, the aim of the present study was to determine dose emission characteristics for low inhalation flows from terbutaline sulphate Turbuhaler. Total emitted dose (TED), fine particle dose (FPD) and mass median aerodynamic diameter (MMAD) of terbutaline sulphate Turbuhaler were determined using inhalation flows of 10-60 L min(-1) and inhaled volume of 4 L. TED and FPD increase significantly with the increase of inhalation flows (p <0.05). Flows had more pronounced effect on FPD than TED, thus, faster inhalation increases respirable amount more than it increases emitted dose. MMAD increases with decrease of inhalation flow until flow of 20L min(-1) then it decreases. In vitro flow dependent dose emission has been demonstrated previously for Turbuhaler for flow rates above 30 L min(-1) but is more pronounced below this flow. Minimal FPD below 30 L min(-1) suggests that during routine use at this flow rate most of emitted dose will impact in mouth. Flow dependent dose emission results suggest that Pharmacopoeias should consider the use variety of inhalation flows rather than one that is equivalent to pressure drop of 4 KPa.

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The relative bioavailability of salbutamol to the lung and body following inhalation can be identified by a urinary pharmacokinetic method. WHAT THIS STUDY ADDS• The amount of terbutaline excreted in the urine during the first 30 min and over the 24 h period post inhalation represents the relative bioavailability of terbutaline to the lung and the body following an inhalation.• Terbutaline study doses can replace a routine salbutamol dose during studies in patients when comparing different inhalation methods. AIMSThe aim of the study was to determine the relative lung and systemic bioavailability of terbutaline. METHODSOn separate days healthy volunteers received 500 mg terbutaline study doses either inhaled from a metered dose inhaler or swallowed as a solution with and without oral charcoal. Urine samples were provided at timed intervals post dosing. RESULTSMean (SD) urinary terbutaline 0.5 h post inhalation, in 12 volunteers, with (IC) and without (I) oral charcoal and oral (O) dosing was 7.4 (2.2), 6.5 (2.1) and 0.2 (0.2) mg. I and IC were similar and both significantly greater than O (P < 0.001). Urinary 24 h terbutaline post I was similar to IC + O. The method was linear and reproducible, similar to that of the urinary salbutamol method. CONCLUSIONSThe urinary salbutamol pharmacokinetic method post inhalation applies to terbutaline. Terbutaline study doses can replace routine salbutamol during these studies when patients are studied.

Some dry powder inhalers have profound inhalation flow rate-dependent dosage emission, and it has been suggested that there are links between the in vitro emitted dose, total lung deposition, and subsequent clinical response. We have measured the in vitro dosage delivery for a combination of budesonide and eformoterol in a new version of the Turbuhaler. At inhalation flow rates of 30, 60, and 90 Lmin(-1), the total dose emission for 10 separate inhalations from each of six inhalers was determined. The aerodynamic characteristics of the emitted dose using inhalation flow rates of 28.3 and 60 Lmin(-1) were measured using the Andersen Cascade Impactor. The mean (SD) emitted dose for budesonide, at 30, 60, and 90 Lmin(-1), was 37.5%(18.2%), 64.4%(16.6%), and 107.4%(36.0%) (of the nominal emitted dose), respectively, and for eformoterol were 38.0%(20.3%), 65.0%(16.8%), and 104.9%(36.2%) (of the nominal emitted dose), respectively. Variability of dose emission characteristics from each inhaler and between inhalers at each flow rate was found. The aerodynamic particle size characterization of the emitted dose at flow rates of 28.3 and 60 Lmin(-1) revealed a mean fine particle dose for budesonide of 11.9% and 28.6% of the nominal emitted dose, respectively, and similarly 10.0% and 26.3% for eformoterol. At 28.3 Lmin(-1), the majority of the emitted dose (54.8% for budesonide and 64.5% for eformoterol) was deposited in the throat and preseparator of the Andersen Cascade Impactor. The mass median aerodynamic diameters for budesonide and eformoterol at 28.3 Lmin(-1) were 3.2 and 3.6 microm, respectively, and similarly at 60 Lmin(-1) were 2.4 and 2.5 microm. The modified Turbuhaler containing a budesonide and eformoterol combined formulation shows intra- and inter-inhaler flow-dependent dosage emission. The clinical significance of the in vitro dose-dependent properties should be investigated.