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From Q2 to QbD: The Influence of Formulation Changes on MDI Performance

Holt J, Hickey AJ, Sandell D.

RDD Asia 2014. Volume , 2014: 33-44.

Abstract:

Metered dose inhalers (MDIs) employ a number of formulation and device components that must be combined optimally to achieve the desired product performance. In the case of generic products, this optimization must be considered in the context of a reference listed drug (RLD). The quantitative sameness (Q2) acceptance range of ± 5% provides a limit to how much a generic product may deviate with respect to the RLD and represents a classical limit, but formal justification of the suitability of the limit is typically lacking. One purpose of the present study was to challenge this arbitrary limit by assessing the impact of a number of variables on product performance. The study aims to establish, from a scientific perspective, the range of variation in each of the factors that can be tolerated while still achieving acceptable performance criteria. The design space can be probed efficiently using design of experiments (DoE). Eighteen MDI batches were manufactured and the effects of the active pharmaceutical ingredient (API) median primary particle size (X50), ethanol content (EtOH), and oleic acid content (OA) investigated. In this paper the results for the four “corner” batches, representing the most extreme combinations of the studied factors, are presented.