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Using a proprietary technology known as the X-ACT system--Active-metering, Cyclone-separator Technology, a novel multi-dose inhaler (Airmax) was developed to provide accurate and consistent dosing and a high-fine particle fraction ofthe drug. Formoterol, present as a blend with lactose monohydrate was delivered from Airmax to obtain a nominal formoterol dose of 6 or 12 microg. The devices were tested using a five-stage liquid impinger and a unit dose sampling apparatus, operated under conditions specified in European Pharmacopoeia (2000). Fine-particle dose (FPD) was defined as the dose of the aerosolized drug particles with an aerodynamic diameter < 5 microm and fine particle fraction (FPF) was the ratio of FPD to the total recovered dose. Dose per actuation was found to be 97.0+/-11.5% label claim (LC) or 5.8+/-0.7 microg (n = 140), and 100+/-9.4% LC or 12+/-1.1 microg (n=440), for the 6 and 12 microg strengths, respectively. The mass median aerodynamic diameter was 2.4+/-0.1 microm (n = 14), the geometric standard deviation 2.1+/-0.1 (n = 14), and FPF 44.4+/-24% (n= 14) for both strengths. Thus, the combination of active metering and cyclone separator produces highly consistent doses of formoterol that have a large respirable fraction.

A novel multi-dose inhaler has been developed to closely approach the characteristics of an "ideal" inhaler. The new device, Airmax, uses proprietary technologies known as the X-ACT system to provide accurate and consistent dosing and excellent lung deposition--even at low inspiratory flow rates--combined with ease of use by the patient. Dose delivery was close to label claim, with relative standard deviation of typically around 5% for through-life emitted mass and around 10% for dose per actuation. At a flow rate (60-70 l/min), which corresponds to 4 kPa pressure drop across the device, the mean fine particle (<5 microm) dose (FPD) from 100, 200 and 400 microg strength budesonide Airmax was around 46, 98 and 244 microg, respectively. The mean FPD from 100 microg strength salbutamol Airmax was approximately 50 microg at the same flow rate. At 30 l/min, the delivered dose from Airmax is over 85% label claim with fine particle fraction of over 35%. Performance was unaffected by shaking or orientation, provided the device was not used completely upside down, and priming was not required. There was no change in dose content uniformity and aerodynamic particle-size distribution after the devices have been stored unwrapped at 30 degrees C/60% RH up to 24 months. Airmax is robust, portable and intuitive to use.

The aim of the study was to investigate the interdependence of carrier particle size, surface treatment of the carrier, and inclusion of fines on the drug delivery from dry power inhaler formulations. Two size fractions (< 63 and 63-90 microm) of alpha-lactose monohydrate were subjected to treatment with 95% (v/v) ethanol to introduce small asperities or cavities onto the otherwise smooth surface without substantially changing the particle shape. After blending with albuterol sulfate [ALB; volume median diameter (VMD), 1.9 microm; geometric standard deviation (GSD), 1.5], the solvent-treated lactose produced a fine particle fraction (FPF; < 6.18 microm) and dispersibility of the drug that was significantly (ANOVA p < 0.01) lower than that which resulted from formulations containing untreated lactose of a similar size fraction, after aerosolization at 60 L min(-1) via a Rotahaler. The two size fractions of the treated lactose resulted in similar deposition profiles of ALB. The effects of such surface asperities or cavities of lactose were offset by introducing a small amount (5% w/w) of smaller-sized lactose (5-10 microm) to the powder formulations. The fine lactose increased the FPF and dispersibility of ALB to such a level that all lactose batches, regardless of particle size or whether solvent treated, produced a similar fraction of aerosolized ALB. The inclusion of recrystallized needle lactose (5-15 microm) was superior to micronized lactose in improving the aerosolization of ALB. The findings of this study indicate that the presence and characteristics of the finer fraction of lactose carrier particles dominate over the particle size and surface smoothness of the carrier particles in determining dispersion and deaggregation of drugs from dry powder formulations for inhalation., (Copyright 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association)