Similar but low deposition in the small conducting airways was observed with each DPI. Subsequent systemic exposure was estimated using a pharmacokinetic model that incorporated Nernst-Brunner dissolution in the conducting airways to predict the net influence of dissolution, mucociliary clearance, and absorption.ĭPIs demonstrated significant in vitro differences in deposition, resulting in large differences in simulated regional deposition in the central conducting airways and the alveolar region. Particle size distributions from three budesonide DPIs, measured with a Next Generation Impactor and Alberta Idealized Throat, were input into a lung deposition model to predict regional deposition. High humidity may cause a reduction in total in vitro lung doses for some pMDI aerosols.Ī combined in vitro - in silico methodology was designed to estimate pharmacokinetics of budesonide delivered via dry powder inhaler. When oriented toward the back of the oral cavity, the filter dose decreased from 46.5% to 36.9% for Ventolin Evohaler (p = 0.005) and from 56.7% to 44.2% for Flovent HFA (p < 0.001) at high humidity relative to low.
Humidity influenced deposition from Ventolin Evohaler and Flovent HFA. Sensitivity to insertion angle and increases in total lung dose variability may be reduced in future products using larger diameter mouthpieces and smaller particles for DPIs and lower-momentum sprays for pMDIs. When directed toward the tongue versus the back of the mouth, the filter dose decreased from 21.9% to 15.6% (percent delivered dose) for Easyhaler Budesonide (p < 0.001), from 46.5% to 26.0% for Ventolin Evohaler (p < 0.001), and from 56.7% to 35.7% for Flovent HFA (p < 0.001) for tests at ambient laboratory humidity. Three of six inhalers showed sensitivity to insertion angle. Deposited drug masses in an Alberta Idealized Throat and downstream filter were quantified through ultraviolet spectroscopy. Three pressurized metered-dose inhalers (pMDIs QVAR®, Ventolin® Evohaler®, and Flovent® HFA) were examined considering the joint effects of insertion angle (as above) and relative humidity at low (15%-25%) and high (>95%) conditions.
Three dry-powder inhalers (DPIs Pulmicort® Turbuhaler®, Budelin® Novolizer®, and Easyhaler® Budesonide) were examined at two insertion angles, one with the inhaler directed toward the back of the oral cavity, the other with the inhaler directed toward the tongue. In this study, we examine the effects of inhaler insertion angle and humidity on deposition from a number of marketed inhalers. The development of accurate in vitro-in vivo correlations requires the consideration of a number of factors in vitro, including the emulation of upper airway geometry, inhalation maneuver, inhaler orientation, and environmental conditions.
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