Characterization of Powder Formulation for Performance Control and Prediction

RESEARCH SUMMARY: There are many scientific challenges that must be overcome to design and manufacture dry powder inhaler (DPI) products that are safe and effective for treating pulmonary diseases. The source of the raw materials (both of active pharmaceutical ingredient (API) and excipients) will have a profound influence on the performance and thus safety and efficacy of DPI products. Specifically, the surface chemistry of the raw materials is known to have a critical impact on the product performance, and the current FDA CMC guidance for metered dose inhalers (MDIs) and DPIs highlights the importance of the surface interactions of API, drug carrier (e.g., lactose) and device in product quality. Investigation of this area is needed to provide guidance for both the brand and generic industries to develop high quality products and tools to evaluate surface chemistry effect for DPI products. These investigations will include a systematic evaluation of a set of analytical tools (e.g., the abbreviated impactor method, full-resolution cascade impactor methods, and/or analytical measurements for material surface properties and their influence on particle interactions) with respect to their capability and relevance in identifying the critical quality attributes (CQAs) of the API and drug carrier materials, as well as in ensuring product quality and performance. The objective is to comprehensively investigate the relationship between processing of API raw materials (i.e., crystals) for inclusion in DPI formulations and product performance. The current CMC guidance for DPIs highlights the importance of the surface interactions of API, drug carrier (e.g., lactose) and device in product quality. These interactions will be affected by the manufacturing processes of API raw materials and their specifications. However, there remains a paucity of scientific data relating raw material quality attributes to product performance. Furthermore, the use and merits of analytical tools to measure surface interfacial properties of the micronized API have not yet been fully explored in the development and quality controls of DPI products. We have discovered and published on a novel and robust predictive quantitative powder deaggregation aerosol equation (PADE) dispersion model that directly correlates interfacial interactions and interparticulate interactions in the dry powder with macroscopic therapeutic aerosol dispersion performance in a quantitative and predictive manner for the four main pulmonary drug classes, including the two drug classes of interest in this project.