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Table 1.

Hypotheses concerning the working mechanism of added lactose fines.

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Table 2.

Particle size distributions of the mixture components (average (SD); n = 3).

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Table 3.

Formulations studied and their total carrier surface coverage (CC) by fine components.

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Figure 1.

Representative SEM images of the pure mixture components.

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Figure 2.

Representative SEM images of mixtures.

Top: mixtures containing 4% budesonide and 4% fine lactose fines. Bottom: mixtures containing 4% budesonide and 4% coarse lactose fines. Images on the right hand side are a magnification of images on the left hand side.

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Figure 3.

The effects of added lactose fines on drug detachment over a range of flow rates.

A) effects of 4% fine lactose fines (FLF) or 4% coarse lactose fines (CLF) on drug detachment of 0.4% budesonide mixtures and B) for 4% budesonide mixtures. Error bars represent maximum and minimum values measured (n = 5).

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Figure 4.

Drug detachment of 4% budesonide mixtures at 30 L/min as a function of added fines content.

FLF = fine lactose fines; CLF = coarse lactose fines. Error bars represent maximum and minimum values measured (n = 5).

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Figure 5.

The influence of mixing order on the effects of added fines on drug detachment.

A) mixtures containing 0.4% budesonide and 4% fine lactose fines (FLF); B) mixtures containing 0.4% budesonide and 4% coarse lactose fines (CLF); C) mixtures containing 4% budesonide and 4% CLF. Drug detachment versus flow rate profiles of mixtures containing only 0.4% or 4% of budesonide (mixed for 5 or 10 minutes) are shown as a reference. Fine components were mixed separately by mixing one component with the carrier for 5 minutes, after which the second component was added and mixing was continued for another 5 minutes. Simult. = drug and fines mixed simultaneously with the carrier material for 5 or 10 minutes. Error bars represent maximum and minimum values measured (n = 5).

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