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Mimicking the APSD from pMDIs: Can it be Done and is it Sufficient to Claim Bioequivalence?

Young PM, Lewis DA, Haghi M, Traini D, Salama RO, Colombo P, Buttini F, Church T, Johnson R, O'Shea H, Forbes B.

RDD Asia 2014. Volume , 2014: 45-54.

Abstract:

Generic inhalation product development focuses on matching the aerodynamic particle size distribution (APSD) of the reference product to increase the likelihood of demonstrating bioequivalence (BE). Pharmacokinetics (and dynamics) is usually only considered at a later clinical stage, with guidelines and requirements varying between geographic regions. To some extent, the lack of clearly defined bioequivalence acceptance criteria in the different regions may hinder formulation and product development. This article provides an overview of the importance of bioequivalence with respect to factors other than APSD (such as the inclusion of excipients) and discusses the impact that these may have on therapeutic efficacy. To investigate this, two pressurized metered dose inhaler (pMDI) formulations were prepared with equivalent APSD but different excipients, so that the final particles contained either drug alone or drug with glycerol. In vitro and in vivo uptake of these formulations was investigated and differences in uptake observed, that could be attributed to formulation excipients indicating that APSD may not be the only factor that should be considered during BE determinations.