Improving In Vitro-In Vivo Correlations in Inhaler Testing

An IVIVC describes a relationship between a result measured in vitro and an aspect of product behaviour observed in vivo. For inhaled products, establishing strong correlations is challenging because drug delivery can be influenced by patient physiology, inhalation technique, disease state, device characteristics and formulation behaviour.

No. Compendial APSD methods remain important for standardised product characterisation and routine quality testing. Realistic APSD methods provide complementary information under more clinically representative conditions.

Standard APSD testing typically uses a pharmacopoeial induction port and constant flow through the inhaler and cascade impactor. Realistic APSD introduces representative throat models and inhalation profiles, while using a mixing inlet to maintain constant impactor flow.

The Alberta Idealised Throat offers a more representative model of mouth-throat deposition than the standard pharmacopoeial induction port while remaining practical and reproducible for laboratory testing.

It decouples the changing flow through the inhaler from the constant flow needed through the impactor, allowing representative inhalation profiles to be used without affecting calibrated impactor operation.

APSD characterises the aerodynamic size distribution of the emitted aerosol. Dissolution testing investigates how the collected drug dissolves after deposition. Together, they provide information about different stages of the inhaled drug-delivery process.

They are included in some product-specific guidances as part of enhanced in vitro or alternative bioequivalence approaches. The exact requirements depend on the individual drug product and the current version of the relevant guidance.