Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma

Abstract

aaDry powder inhalers (DPI) are increasingly used for aerosol delivery to the airways for the reasons that they are easy-to-use with no requirements of co-ordination, they are convenient and are without propellants or irritants. In addition, an ideal device should provide a high and predictable airway dose and a low pharyngeal dose. In all DPIs the inspiratory airflow of a patient provides the energy source to disperse the agglomerates of micronized powder and to move the respirable particles from the body of the inhaler to the lung. The drug is drawn from a holding bin of pure drug, or is available as drug particles mixed in a bulking agent such as lactose, which helps dispersion and improves the dose-to-dose reproducibility. It is a fundamental prerequisite for use that the patient can generate enough airflow energy through the device to achieve sufficient dispersion of the drug agglomerates. This interaction between the inhalation effort provided and the aerosolizing property is unique to the different designs of DPIs. The present study was undertaken to examine the likely lung dose, its reproducibility, and the effort dependency in children using two common DPIs: 1) the Turbuhaler is a widely used DPI which is easy-to-use and provides a high lung dose [1,2], yet apparently with flow dependent drug delivery [3][4][5]; and 2) the Diskus inhaler is the most recent addition to the range of multidose powder inhalers available for the delivery of β 2 -agonists or corticosteroids. It contains 60 factory-dispensed drug doses in a lactose carrier. The Diskus was designed as a low resistance device similar in aerosolizing property to the Diskhaler [6].We have studied the amount of aerosol obtained from the Diskus and Turbuhaler in asthmatic children of 4 and 8 yrs. The Turbuhaler is in most countries approved for use in children of >5 yrs, while the Diskus is approved for use down to 3 yrs of age. We therefore chose to consider children of 4 yrs as the lower limit for comparison, as this 1 yr difference to the recommended lower age is unlikely to affect the expected flow performance of the children. Our approach has been to record inhalation profiles from asthmatic children. We have used these profiles in an inhalation simulator [7] ( fig. 1) to draw doses from both the Diskus and Turbuhaler inhalers and subsequently to assess the particle size distribution of the drug using a cascade impactor. This method has enabled us to measure the emitted dose and the fractions of coarse and fine particles of drug that each child would be capable of drawing from these devices. Methods PatientsTwenty children aged 4 yrs and 18 children aged 8 yrs with asymptomatic asthma were recruited to the study. Informed consent was obtained from parents or guardians Full profiles of inhalation pressure versus time were recorded in 18 4 yr old and 18 8 yr old asthmatic children through Diskus and Turbuhaler inhalers. These data were used in an inhalation profile simulator to assess drug delivery from both a Diskus inhaler and a Turbuhaler inha...

Inspiratory flow rates at different levels of resistance in elderly COPD patients

“…The present data demonstrate that 30% of the elderly population were not able to reach the arbitrary cut-off flow of 45 L?min -1 when using a Turbuhaler1, while only 20 and 12.5% of the population had similar problems with the Diskus1 and Aeroliser1, respectively. Turbuhaler1 and Aeroliser1 are less effective at a PIF ,60 L?min -1 , whereas the Diskus1 seems to have an equal effect at a PIF 30-60 L?min -1 [6,[22][23][24][25][26][27][28][29][30]. This could mean that, in contrast to the Diskus1, the number of patients with subtherapeutic flows over the Aeroliser1 or Turbuhaler1 is even underestimated.…”

“…PIFs .60 L?min -1 are generally believed to be the optimal flows for most of the devices, while PIFs ,30 L?min -1 are accepted to be insufficient for generating any effect [6,[22][23][24][25][26][27][28][29][30]. As there is still discussion about the effectiveness of PIFs ranging 30-60 L?min -1 [14,31,32], an arbitrary cut-off at a PIF of 45 L?min -1 was made in order to distinguish therapeutic flows from subtherapeutic levels.…”

Peak inspiratory flow rate and slope of the inhalation profiles in dry powder inhalers

“…However, it is not the only characteristic parameter. Since the PIFR is mostly achieved after the release of the powder, the slope of the pressure profile (in kPa?s -1 ) has also been described as an important determinant [6,9,10]. The present investigation was undertaken to assess whether the PIFR through a Diskus1 and a Turbuhaler1 inhaler could be used to predict the slope of the inhalation pressure profile.…”

“…In vitro device evaluations showed that the emitted dose and fine particle mass of the Turbuhaler1 (higher resistivity) increase at higher peak inspiratory flow rates (PIFRs) [5,6], whereas the Diskus1 (lower resistivity) provided a more consistent dose delivery, relatively independent of different airflows [6,7]. However, there was therapeutic equivalence of salbutamol given via these devices [8].…”

Micronized Drug Adhesion and Detachment from Surfaces: Effect of Loading Conditions

“…The FPF is a maximum at 1 min at 70.07 ± 4.71%. Comparing this to the commercial budesonide turbuhaler DPI, the FPF is reported to be 44% (Ball et al 2002;Bisgaard et al 1998;Thorsson et al 1994;Borgstrom et al 1994). While FPF is almost similar at 10 and 30 min drug loading, at 55.91 ± 6.81% and 55.97 ± 5.97%, respectively.…”