Scintigraphic comparison of budesonide deposition from two dry powder inhalers

Abstract

Chlorofluorocarbons (CFCs), used in metered dose inhalers (MDIs), have been identified as being deleterious to the environment leading to a ban on their production. Dry powder inhalers (DPIs) are a widely used alternative to MDIs. One disadvantage of DPIs is that in vivo lung deposition can be influenced by the patient's inspiratory flow rate. The ASTA Medica multi-dose dry powder inhaler (AM-MDPI) has been designed to offer low resistance on inhalation, so that asthmatic patients can achieve inhaled flow rates of~90 L . min -1 . The aim of the study was to evaluate the in vivo deposition of budesonide from the AM-MDPI at different flow rates and to compare this with delivery from a Turbuhaler DPI at a high flow rate. The study was a scintigraphic, randomized, crossover study in which 13 healthy volunteers inhaled a single 200 mg dose of radiolabelled budesonide on four separate occasions with a minimum 44-h washout period between dosings.At the lowest flow rate of 54 L . min -1 , comparable to that for the Turbuhaler (58 L . min ) the AM-MDPI delivered significantly more drug to the lung (median 32.1% of metered dose) than at 65 L . min -1 or 54 L . min -1 (median 25.0% and 19.9% of metered dose, respectively), thus demonstrating flow rate dependence. The pattern of regional lung deposition from the AM-MDPI was similar for all three inhalation manoeuvres.It was concluded that the ASTA Medica multi-dose dry powder inhaler achieves at least as much deposition of budesonide in the lungs as a Turbuhaler when used at similar inspiratory flow rates. Eur Respir J 2000; 16: 178±183.

Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates

“…(67,68) In the previous validation study of Tian et al, (61) acceptable agreement was found between the in vivo results of Newman et al (62) and CFD computed airway predictions transferred to 2D planar images for the Novolizer inhaler, which was considered only at the PIFR of 99 LPM (fast inhalation), as well as a softmist inhaler also considered at a single flow rate. The methods established in the previous study of Tian et al (61) are repeated in the current study to evaluate the more challenging scenario of a single DPI evaluated at multiple flow rates generating different aerosol size distributions and tested in two separate airway geometries.…”

“…Regional lung deposition was determined by dividing the 2D planar image into boxes representing the central, intermediate, and peripheral lung. The imaging template used in the study of Newman et al (62) was previously defined with an image provided in the study of Newman et al (65) and compared to an anatomical drawing in Newman et al (66) The regional deposition data reported by Newman et al (62) are percentages of the metered dose (powder loaded in the inhaler) and therefore include the effect of drug retained in the inhaler and not aerosolized. This fraction of the dose was not simulated during the CFD studies.…”

“…(1) To validate CFD model predictions throughout the airways, an in vivo case study was sought that considered use of a DPI expected to be flow rate dependent across multiple inhalation waveforms. The in vivo case study selected was that of Newman et al (62) who considered 14 healthy subjects using a budesonide Novolizer DPI (200 lg; Meda, Pharmaceuticals, Somerset, NJ) with controlled and measured breathing conditions. Three separate experiments were conducted in which each of the 14 subjects used the Novolizer and targeted either slow, intermediate, or fast inhalation waveforms resulting in measured peak inspiratory flow rates (PIFR) of 99, 65, and 54 L/min (LPM), respectively.…”

“…As described, subjects in the in vivo study of Newman et al (62) were trained to inhale through the DPI at three different flow rates, resulting in measured mean PIFRs of 99, 65, and 54 LPM. For each of the three inhalation waveforms, spirometry recorded an inhalation volume of approximately 3 L. Following inhalation, subjects were instructed to perform a 10 s breath hold, which was verified by the spirometric data.…”

“…CFD predictions are compared with the 2D gamma scintigraphy in vivo study of Newman et al (62) employing the Novolizer DPI. As with previous studies, in vitro experiments are first used to characterize the initial aerosol size distribution at multiple inhalation flow rates.…”