Confirming bioequivalence for a generic tiotropium dry powder inhalers

Pharmacokinetic (PK) profiling is a central strategy for the demonstration of bioequivalence in generic dry powder inhaler development.

This paper describes a study in which in vitro testing under clinically relevant conditions, an in silico regional deposition model and a physiologically-based PK simulation model were used together to compare Test and Reference tiotropium products. In vitro testing detected significant batch to batch variability in the Reference product while in silico and PK data, in combination, highlighted the potential for variability in peripheral dose deposition to impact PK profile. The developed in silico model, once validated, has considerable potential to elucidate correlations between in vitro and in vivo data and help generic developers to establish and demonstrate robust bioequivalence.