Aerodynamic Particle Size Distribution (APSD)

Together with delivered dose, aerodynamic particle size distribution (APSD) is typically identified as a Critical Quality Attribute (CQA) for orally inhaled and nasal drug products (OINDPs) making it a primary focus for in vitro characterisation. The APSD of an OINDP defines how particles behave in a moving air stream. It is intuitively relevant to the understanding of likely lung deposition and hence potential drug efficacy. Typically particles should be in the range of 1 to 5 microns to be effective, any larger than 5 microns and they are likely to impact the oropharynx and be swallowed, any smaller than 1 micron and it is possible that the particles will remain entrained in the air system.

Aerodynamic Particle Size Distribution

Please select an OINDP type for further information about Aerodynamic Particle Size Distribution (APSD) measurement.

APSD of Metered Dose Inhalers (MDIs)
APSD of Metered Dose Inhalers (MDIs)

The APSD testing of MDIs is typically performed at a flow rate of 28.3 L/min when using an ACI or 30 L/min when using an NGI. For Breath Actuated MDIs (BAIs) a Breath Actuation Controller may also be used to generate a time delay.

However, it must be noted that when add-on devices such as spacers or valved holding chambers (VHCs) are used, the APSD characteristics may be substantially altered from what is emitted when the MDI is used alone and must be assessed appropriately.

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APSD of Dry Powder Inhalers (DPIs)
APSD of Dry Powder Inhalers (DPIs)

The APSD measurement of DPIs is typically performed under the same conditions as DDU testing, however a Preseparator is typically interposed between the induction port and stage 0 of cascade impactor to capture the large, non-inhalable carrier particles, to prevent impactor over-loading.

As for delivered dose testing of DPIs, test flow rate is set on the basis of a 4 kPa pressure drop across the device, to approximate the mean patient inhalation flow rate achieved during clinical use.

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APSD of Nebulisers
APSD of Nebulisers

For devices such as nebulisers, the evaporation of droplets exacerbated by the thermal mass of the impactor can be a problem, especially for drugs in solution. Loss of solvent reduces droplet size, producing artificially low APSD measurements, compromising the integrity of the resulting data. Cooling the impactor to approximately 5°C is the recommended method for overcoming this problem.

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APSD of Aqueous Droplet Inhalers (ADIs)
APSD of Aqueous Droplet Inhalers (ADIs)

For ADIs as for nebulisers, the evaporation of droplets exacerbated by the thermal mass of the impactor can be a problem. Loss of solvent reduces droplet size, producing artificially low APSD measurements, compromising the integrity of the resulting data. Cooling the impactor to approximately 5°C is the recommended method for overcoming this problem.

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APSD of Nasal Products
APSD of Nasal Products

Nasal sprays, nasal aerosols and nasal powders typically produce droplets in the range of 20-200 microns, which is outside the effective range of cascade impactors. However, each may deliver a proportion of fine droplets in the <10 micron range. It is important to quantify this FPD since it can penetrate beyond the nasal tract and into the lower respiratory tract or lungs, which may be undesirable.

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