Mechanisms by which Nanoparticle Agglomerates Enhance Aerosol Performance

University Of Kansas Center For Research Inc, Lawrence KS

Investigators

Abstract

Intellectual Merit Pulmonary delivery of therapeutics represents a significant area of growth in the pharmaceutical industry. Dry powder aerosols represent the formulation of choice due to improved aerosol delivery and drug stability compared to nebulized or metered solutions. Obtaining dry powders typically requires processing techniques such as milling or spray drying that yield polydisperse powders with large aerodynamic diameter (>5 ìm), poor dispersibility and inadequate flow characteristics. Furthermore, processed particles (~1-5 ìm) must dissolve or disperse rapidly once deposited in the lung to avoid being cleared by cilia or by alveolar macrophages. Nanoparticles possess desirable properties for avoiding these clearance mechanisms; however, nanoparticle aerosols are typically exhaled due to their small size. Nanoparticle agglomeration has been identified as an effective means to incorporate the desired micro- and nanostructure into dry powder formulations. Nanoparticle agglomerates possess a low density microstructure to enhance lung deposition. Furthermore, the nanostructure of these particle assemblies dramatically improves the dissolution rate of drugs compared to microparticles of a similar size. In objectilve 1, processing conditions will be systematically studied and agglomerates characterized for two types of drug nanoparticles. Objective 2 will analyze the powder properties of nanoparticle agglomerates compared to micronized drug and correlate these properties to physicochemical traits of the agglomerates. Broader Impacts The proposed research will broadly impact students, researchers, industry, and ultimately patients. Defining nanoparticle agglomeration as a pharmaceutical processing modality will provide new insights to researchers working in nanotechnology, pharmaceuticals, particle processing, and aerosol science. Flocculation of colloids is currently applied in diverse industries such as waste recovery, food and health care product processing, and microbial separations. These industries will also benefit from dissemination of the results of studies proposed here. The educational cornerstone of this proposal is a program entitled ?Education through Outreach? (EtO) aimed to introduce high school students to the role of scientists and engineers in product development by enlisting them to present projects to junior high students. The program aims to capture students at critical educational crossroads as they transition to high school or to college. This educational program will enhance student awareness of science and engineering in everyday products, spurring them on to STEM-based careers.