The interaction between the oropharyngeal geometry and aerosols via pressurised metered dose inhalers.

PURPOSE: This study investigated the effect of oropharyngeal geometry on inhaled aerosol characteristics via pressurised metered dose inhalers (pMDIs), both with or without spacers. METHODS: Seven adult oropharyngeal models with different centreline lengths, total volumes, and degrees of constriction were employed as induction ports for a laser diffraction particle size analyser and cascade impactor. Particle size change over time, mass median aerodynamic diameter (MMAD), average median volume diameter (D(V)50), inhaled doses, and oropharyngeal depositions (percentage of the nominal dose) for aerosols via suspension and ultrafine pMDIs with or without spacers at 30 l/min airflow were determined. RESULTS: Variations in oropharyngeal geometry caused significant variations in inhaled particle size distributions, doses, oropharyngeal drug depositions, and particle size change over time when pMDIs were used without spacers. However, inhaled aerosol characteristics had marginal variations for the ultrafine pMDI plus large volume spacer (MMAD range: 0.69-0.78 microm, D(V)50 range: 1.27-1.36 microm, inhaled dose range: 46.46-52.92%). It was found that the amounts of inhaled aerosol particles with aerodynamic size of less than 0.83 microm via pMDIs plus large volume spacer were slightly affected by the oropharyngeal geometry. CONCLUSION: Inhaling ultrafine aerosols via spacers may reduce the effect of oropharyngeal geometry on inhaled aerosol properties.

Investigating improving powder deagglomeration via dry powder inhalers at a low inspiratory flow rate by employing add-on spacers.

The aim of this study was to investigate whether small add-on spacers alone or equipped with a passive deagglomerating component would improve aerosol performances of passive low airflow resistance dry powder inhalers (DPIs) at a low inhalation flow rate. Depositions of beclometasone dipropionate (BDP) and salbutamol sulphate (SS) via the Asmabec Clickhaler and Asmasal Clickhaler at 30 L/min airflow rate in an oropharyngeal model and attached filter were determined. Three add-on spacers, one with 5.0 cm length, and the other with the same features but incorporating a fine mesh, and the third one with the length of 8.5 cm (long add-on spacer) were used. Incorporating mesh did not improve the filter dose for SS, and significantly reduced this dose for BDP. The long add-on spacer was the most efficient spacer as it had minimal effects on the filter doses, also significantly reduced drug depositions in the model. In conclusion, an optimum length of an add-on spacer is required to minimise oropharyngeal drug deposition via a low airflow resistance DPI at a low inspiratory flow rate without considerable reduction of the respirable dose. Incorporating sieves within add-on spacers may diminish aerosol performances of the DPIs at low airflow rates.

Effect of oropharyngeal length in drug lung delivery via suspension pressurized metered dose inhalers.

PURPOSE: To determine the effect of the oropharyngeal length in adults on the lung dose of a suspension pressurized metered dose inhaler, and whether employing small volume spacers can alter this role. METHODS: Depositions of Ventolin Evohaler (100) microg in the oropharyngeal models of two healthy adult subjects with 17.1 cm (short cast) and 19.9 cm (long cast) centerline lengths via three small volume spacers [two spacers with 3 cm effective length but one with 6.5 cm2 (L3) and the other with 24.6 cm2 (L3W) cross sections, and the Optimiser] were studied. RESULTS: Without using spacers, lung dose of the long cast (19.52 +/- 2.32 microg, mean +/- standard deviation) was significantly larger than that for the short cast (8.08 +/- 1.01 microg, p < 0.006). However, using the L3 spacer with the short cast made the lung dose (18.59 +/- 3.33 microg) similar to that for the long cast alone. Lung doses of the short cast (20.43 +/- 1.42 microg) and the long cast (30.81 +/- 1.84 microg) with the L3W spacer were similar to those with the L3 spacer. However, using the Optimiser spacer increased the lung dose for the short cast (22.27 +/- 6.03 microg) and significantly for the long cast (35.61 +/- 2.19 microg, p < 0.006) compared to those for the L3 spacer. Using spacers increased drug deposition in the oropharynx part of the short cast, and this reduced the lung dose compared to that for the long cast. CONCLUSION: The oropharyngeal length in adults may affect the lung dose via the pMDIs, which may not be eliminated by using small volume spacers.

Suitability of the upper airway models obtained from MRI studies in simulating drug lung deposition from inhalers.

PURPOSE: In this study, the suitability of the upper airway models, obtained by applying a magnetic resonance imaging method, in simulating in vivo aerosol deposition data is determined. METHODS: Depositions of salbutamol sulfate from two nebulizers in two models, one with constriction at the oropharynx (the constricted cast) and another model without that constriction (the wide cast), were determined. RESULTS: For the Sidestream and Ventstream nebulizer, 76 +/- 3% (mean +/- standard deviation) and 81 +/- 2% of the emitted dose deposited in the constricted cast, whereas 51 +/- 2% and 49 +/- 3% of the emitted dose deposited in the wide cast, respectively. These values were in good agreement with in vivo data. Mostly, increasing nebulizer charge volume (by normal saline) from 2.5 ml to 5 ml increased significantly the lung dose. However, the lung doses from the Sidestream and Ventstream nebulizer with 2.5 ml charge volume via the wide cast were (1.37 +/- 0.06 and 1.38 +/- 0.05 mg) significantly larger than those for the constricted cast with 5 ml charge volume (0.87 +/- 0.15 and 0.86 +/- 0.21 mg, respectively) (p = 0.005). CONCLUSIONS: The upper airway models closely simulated the in vivo deposition data. Optimizing the upper airway posture during inhalation via the nebulizers would be more efficient in increasing drug lung delivery than diluting their contents.