There are many scientific challenges that need to be overcome to manufacture carrier based drypowder inhaler (DPI) products that are safe and therapeutic for treating respiratory diseases. Of these,controlling the manufacture and critical quality attributes (CQAs) of raw materials (both the activepharmaceutical ingredient and excipients) is critical to the successful development of a safe andefficacious DPI product. In this proposal, we seek to determine how primary crystallization andsecondary processing of APIs directly influence formulation structure and product functionality ofsingle component and combination based DPI products. The major research objective is to identifyand provide a science based understanding of the CQAs of primary and secondary processed APIs. Agreater understanding of this relationship between primary crystallization, its CQAs and their influenceon surface interfacial properties of micronized APIs, will provide the necessary science and tools toenable greater control of product safety, efficacy, potency, quality and performance. The explorationinto the relationship between the physicochemical properties of primary crystals, surface interfacialproperties of secondary processed micronized API and the CQAs of these particles will aid the FDA todirect both brand and generic industries to define quality and functionality in DPI drug products.
This project addresses several issues of critical importance in regulatory science of carrier based dry powder inhaler formulations. These include how primary crystallization of active pharmaceutical ingredients (APIs) and their critical quality attributes influence final product quality and performance, how the consistency and critical quality attributes of the micronized API is dependent on the manufacturing of the primary API source, and how dynamic changes in the the surface interfacial properties of APIs post-micronizaiton requires an understanding of the requirements for laagering and quarantining of micronized APIs. These studies will show the use and merits of specific analytical tools to measure unique physicochemical, mechanical and interfacial properties and provide the relevant guidance to both brand and generic industries in advancing quality by design approaches for product development and quality control of DPI products.
