Until recently nebulisers have been classified as medical devices and not ‘integrated products’ like dry powder and metered dose inhalers, because they can be used with a variety of drug formulations. However, this is changing and the new ISO 27427:2010 specifies more stringent requirements for the ‘safety, performance and testing of general purpose nebulising systems that are intended for continuous or breath-actuated delivery of liquids, in an aerosol form’.
UK-based Melbourn Scientific, a provider of cGMP analytical and formulation services to the pharmaceutical, biotech and healthcare industries, investigated the impact of temperature on aerodynamic particle size and has concluded that cooling the NGI reduces evaporation.
The two major factors that affect drug delivery with a nebuliser are usage time and particle size. Particle size is crucial as it determines where the drug is deposited within the respiratory tract. It is known that during testing with an NGI heat transfer can cause evaporation, which reduces the particle size, and this can distort the findings.
Researchers at Melbourn Scientific used a PARI LC Sprint jet nebuliser with a flow rate of 15L/min and nebulisation was continued until the sample had been exhausted. They compared the fine particle fraction of two formulations at different temperatures: ambient laboratory conditions after cooling the NGI in a refrigerator at 2–8°C, and within an NGI cooler at 10°C, 7.5°C and 5°C.
The data showed that there is a decrease in the fine particle fraction at lower temperatures with profiles showing a bias towards the smaller particle sizes at ambient conditions. The nebuliser monograph in the Pharmaeuropa suggests that the NGI needs to be cooled to 5–10°C to reduce evaporation, and data obtained by Melbourn justifies this.
Additionally the study demonstrated that the NGI cooler is more effective than pre-refrigeration of the NGI at reducing evaporation of the nebuliser solution.
The researchers concluded that temperature affects different solutions and suspensions in different ways so the influence of formulation on nebuliser performance at different temperatures is an avenue for future study.
