Influence of single versus multiple actuations on the particle size distribution of beclometasone dipropionate metered-dose inhalers.

The particle size distributions of beclometasone dipropionate delivered from Becotide and Respocort inhalers after single and multiple actuations were investigated using the Andersen Mark II Cascade impactor and the drug was quantified using high performance liquid chromatography. The fine particle mass and the mass median aerodynamic diameter were calculated. An apparent increase in mass median aerodynamic diameter was observed when the number of actuations increased. In addition, the fine particle mass decreased as the number of actuations increased. When performing and analysing cascade impaction study data differences between single versus multiple actuations must be considered. Regulatory guidelines should be amended to stipulate the number of actuations to be loaded into devices used to evaluate the particle size distribution of inhaled aerosol products.

Influence of respiratory spacer devices on aerodynamic particle size distribution and fine particle mass of beclomethasone from metered-dose inhalers.

Respiratory spacer devices are used mainly with pressurized metered dose inhalers, especially those containing corticosteroids, to assist with patient coordination and reduce oropharyngeal side effects. This investigation examines the influence of different spacer devices on the delivered fine particle mass (aerodynamic diameter of <3.3 microm and <4.7 microm) of the corticosteroid beclomethasone dipropionate, which approximates the respirable dose. The Anderson Mark II Cascade Impactor was used to characterise the deposition of single doses of beclomethasone dipropionate from several metered-dose inhalers. Following actuation of one single dose the amount of beclomethasone dipropionate deposited on each stage of the impactor was quantified using reverse phase high-performance liquid chromatography and ultraviolet detection. The fine particle mass smaller than 4.7 microm for Respocort delivered by the Sanner and Fisonair spacer devices was 77.7% and 41.3% higher (p < 0.04), respectively, than the metered-dose inhaler alone, while the Breathatech spacer delivered 21.4% lower (p < 0.01). The fine particle mass of Becotide delivered by the Sanner, Fisonair, Nebuhaler, and Volumatic spacer devices were 81%, 42.4%, 46.9%, and 32.8% higher (p < 0.008), respectively, than be metered dose inhaler alone. The fine particle mass for Becloforte delivered by the Sanner, Fisonair, and Volumatic spacer devices was 82.8%, 36.9%, and 48.0% higher (p < 0.009) than that delivered by metered dose inhaler alone. This study suggests that there are significant differences in the fine particle mass of beclomethasone dipropionate delivered by respiratory spacer devices when used in conjunction with commercially available metered dose inhalers of this drug.

In-vitro characterisation of metered dose inhaler versus dry powder inhaler glucocorticoid products: influence of inspiratory flow rates.

PURPOSE: To study the influence of inspiratory flow rate on the fine particle mass and the particle size distribution for metered dose inhaler (MDI) and dry powder inhaler (DPI) glucocorticoid products, in vitro. To compare the performance of MDI and DPI inhalers containing the same drug and strength at an impaction flow rate of 60 L/min. METHODS: The Marple Miller cascade impactor model 150 and 160 were used to characterise several glucocorticoid MDI and DPI products at different simulated inspiratory flow rates (30 L/min, 60 L/min and 90 L/min). Following the actuation of one single inhaler puff the amount of drug deposited in each stage of the impactor was quantified using high performance liquid chromatography with UV detection at 242 nm. The size distribution of the primary particles of DPI products was measured by laser diffraction. RESULTS: DPIs were significantly more dependent on impaction flow rate than MDIs. Except for Pulmicort(R), the fine particle mass FPM delivered from the MDI products was significantly higher than that delivered from the DPI aerosols. CONCLUSIONS: Although the metered dose inhaler is the older technology it exhibits greater respirable dose in vitro than newer dry powder inhaler devices. Care should be taken when shifting from one inhaler dosage form to another because this may affect the actual dose delivered to the lung. Further in vivo studies may be warranted in light of these findings.