Alexander K. Iula, Cynthia L. Flynn, and Frank Deluccia
Rhone-Poulenc Rorer Pharmaceuticals Inc., Collegeville, Pennsylvania
Abstract
This in vitro study compared the dose delivery and particle size distribution performance of triamcinolone acetonide from an Azmacort® metered-dose inhaler (MDI) in combination with four different spacer devices. The four spacer devices studied were the Azmacort® integrated spacer, the AeroChamber®, the InspirEase®, and the Microspacer®. For each MDI/spacer combination, at least two units from each of three lots of Azmacort were used for the determination of dose delivery and particle size distribution. The total delivery of triamcinolone acetonide was assessed using the recently proposed United States Pharmacopeia dosage unit sampling apparatus for MDIs at a flow rate of 60 L/min. Particle size distribution and respirable dose were assessed using the Andersen 1 ACFM Non-viable Ambient Particle Sizing Sampler (Model 20-800). The relative delivery of triamcinolone acetonide from the Azmacort integrated spacer, AeroChamber, InspirEase, and Microspacer, without a delay, was 100%, 72.9%, 16.7%, and 96.6%, respectively. Similarly, dose delivery with a 1-second delay between actuation and sample collection was 33.6%, 12.2%, 20.1%, and 22.9% of the original result, respectively. All the spacers studied changed the particle size distribution of the dose. Each spacer reduced, although not to the same degree, the deposition of triamcinolone acetonide in the throat induction port of the cascade impactor. The highest respirable dose (<5.8 μm) of triamcinolone acetonide was delivered by the Azmacort integrated spacer (68.8%), followed by the Microspacer (51.0%), AeroChamber (50.2%), and InspirEase (11.9%). Thus the Azmacort integrated spacer when used in combination with the Azmacort MDI delivered the highest total dose and greatest respirable dose of triamcinolone acetonide. The differences demonstrated in the performance (dose and particle size) among spacer devices (dose and particle size) in this in vitro study underscore the importance of evaluating drug delivery of all MDI/spacer combinations intended for drug administration. Clinical trials are needed to test the implication of the results that different MDI/spacer combinations may produce variable clinical responses in vivo.
Discussion & Conclusions
MicroSpacer® outperformed both Aerochamber and InspirEase regarding delivery of total and respirable dose delivered to the lungs (see page 552). This was a published study.