Copley Scientific CEO Mark Copley answers questions about the importance of the test environment for OIP testing
Why is the test environment so important for inhaler testing?
Due to a broad range of factors, including interaction between formulation, device, and patient, orally inhaled product (OIP) testing is naturally more variable than testing for simple dosage forms such as tablets. Effective control of the test environment — temperature, relative humidity (RH) and electrostatics –is one way to reduce variability in inhaler testing and can result in significant savings of time and money.
Failure to control the inhaler testing environment will likely translate into variability of test data generated, which can compromise discriminating power and subsequent decision making. In QC testing, a reduction in data accuracy can make it harder to reliably confirm adherence to tolerances, increasing the risk of erroneous, out-of-specification results. In R&D testing, variable data can compromise understanding of the impact of subtle changes to formulation and device variables; in the case of generics, variable data make it harder to establish bioequivalence.
Although the inherent variability of inhaler testing quickly becomes evident to anyone working in the field, and there is much advice on how to mitigate the effects, the consequences of environmental variability are complex to understand and easy to underestimate due to the large array of confounding variables.
How do environmental factors affect inhaler testing results?
Variability in the test environment separately influences both drug delivery and measurement. The resulting effects are various and intertwined, can be OIP-specific, and are ultimately unpredictable.
In both delivered dose uniformity (DDU) testing and cascade impaction, temperature, RH, and electrostatics all influence aerosolization and dose release, potentially introducing variability in the characteristics of the resulting dose and impacting metrics measured by both techniques.
Additionally, in cascade impaction, which is a core inhaler testing technique, environmental conditions can influence measurement precision. The separation performance of a cascade impactor is a function of inlet volumetric flow rate; therefore, changes in air density, which is affected by the temperature of the entrained flow, and electrostatic charge dissipation can influence stage-to-stage particle deposition. If those factors are not controlled and/or accounted for, they will affect the recorded aerodynamic particle size distribution (APSD).
A study of environmental factors in cascade testing of a nebulizerthat was presented at RDD Europe 2007 demonstrated changes in MMAD of about 5% arising from relatively modest environmental changes that could realistically arise from diurnal or seasonal variation in a poorly controlled lab.
