From milling to particle engineering: Formulations for dry powder inhalers
Abstract
Dry powder inhalers (DPIs) are alternative devices to the commonly used propellant driven metered dose inhalers. Since DPIs typically rely on patient driven inspiration to entrain powder from the device, formulations that requires minimal dependence on the device and patient is the desired end product. By first understanding the consequences of the milling process used to produce particles in the required size range for efficient delivery to the lungs, a criteria can be set whereby desired properties of the drug can be achieved. Griseofulvin and ketoconazole were used as model pharmaceutical compounds for assessing the impact on the surface and bulk properties due to milling. The unique behavior displayed post-cryomilling by griseofulvin merited further studies to better gauge the intermediary states that may be generated during the milling process. Once the final characteristics of the drug substance has been established, desired or undesired, understanding the interaction between the drug and carrier surface is needed. A newly derived surface energy distribution method from the literature was applied to lactose carriers and salbutamol sulphate to assess the interactions generated between the two particles and ascertain the effect of the interactions on the final outcome in-vitro. Particle engineering techniques allow the manipulation and control of the particle's characteristics, not commonly found in typical batch production techniques used in the industry today. A microfabrication technique, derived from the microelectromechanical systems industry, was explored for producing homogeneous carrier particles with predetermined sizes and morphologies. A DPI passive device comparison was undertaken to assess the device dependence of these carriers along with how surface modifications may impact the fine particle fraction generated. Finally, fabricating homogeneous drug particles using the hydrogel template method and a modified soft lithographic technique was investigated to determine if crystalline particles can be generated with shape, surface, and size control for potential carrier and excipient-free formulations.
Degree
Ph.D.
Advisors
Park, Purdue University.
Subject Area
Pharmacy sciences
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