With the growing trend for regulatory authorities to link approval of the formulation with the delivery device there has been an increased focus on the need for accurate nebuliser testing.
A study by Melbourn Scientific has confirmed that an improved protocol is needed when testing with a Next Generation Impactor (NGI) as temperature generated by the nebuliser can impact the droplet size.
Until recently nebulisers had been classified as medical devices and not integrated products like dry powder and metered dose inhalers, as they can be used with a variety of drug formulations.
This is changing however 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".
Melbourn Scientific 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 a 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.
The study also demonstrated that the NGI cooler is more effective than pre-refrigeration of the NGI at reducing evaporation of the nebuliser solution.
Researchers conclude that temperature affects different solutions and suspensions in different ways so the influence of formulation on nebuliser performance at different temperatures is another avenue for future study.