Request Copyright Permission

Demonstrating Q3 Structural Equivalence of Dry Powder Inhaler Blends: New Analytical Concepts and Techniques

Price R, Farias G, Ganley W, Shur J.

Respiratory Drug Delivery 2018. Volume 1, 2018: 265-276.

Abstract:

The assessment of bioequivalence (BE) of locally acting drug products has been a long-standing challenge for both the pharmaceutical industry and regulatory authorities. Typically, clinical endpoint BE trials have provided the only option for generating inter-product comparisons for topical creams and ointments. Given the insensitivity and logistic challenges associated with such studies, there has been an increasing effort to identify alternative pathways that can reliably ensure equivalent safety, product performance, and quality of topical products, including locally acting drugs delivered by aerosol inhalation. This paper introduces the concept and assesses the possible approaches for characterising in vitro based structural equivalence of drug formulations delivered as aerosolized doses (Q3) that can be related to the therapeutic equivalence of orally inhaled drug products (OIDP). This provides the possibility of a new regulatory pathway for a range of locally acting dosage forms without the need to conduct a comparative clinical endpoint study. The structural differences in the arrangement of matter and state(s) of aggregation within the formulated and aerosolized form of these products can depend on physicochemical properties of active and inactive materials, device characteristics and processing history, including manufacturing processes and storage conditions. These differences in Q3 at both a microscopic and macroscopic scale can be characterized using a combination of orthogonal in vitro and/or ex vivo techniques. Some of the techniques currently under assessment for characterising Q3 for OIDPs include the use of morphology-directed Raman spectroscopy (MDRS), surface-mapping Raman spectroscopy, and integrated structural measurements through in vitro dissolution kinetics. For certain OIDPs, an ongoing discussion centers on how best to investigate and characterize Q3 for the different dosage forms and to demonstrate the validity of Q3 for BE determinations.