Nanoparticle Agglomeration via Ionic Colloidal Destabilization as a Novel Approach to Dry Powder Formulations for Pulmonary Drug Delivery

Abstract

Efficient administration of poorly water soluble drugs represents a leading challenge in pulmonary medicine. This route of administration has been used for steroidal treatments for some time, but with room for advancement. New inhalable medicines require a more reliable and effective dosing regimen due to narrow therapeutic indices, and specific and enhanced deposition in the lungs is also desired. This thesis investigates a general method for producing micron sized dry powders for a general class of drugs, poorly water soluble small molecule drugs, for their use in pulmonary drug delivery. Formulation methods already exist for inhalable aerosols, but the resulting powders often show limited deposition efficiency in the deep lung. In this body of work, an alternative formulation strategy is provided for inhalable dry powders using nanoparticle agglomeration that results in a potentially more efficient line of therapy. The model drug used in this study was nifedipine, a well known calcium channel blocker used to treat various symptoms of hypertension. The results indicated that nanoparticle agglomeration is a viable means of creating dry powders with suitable characteristics for pulmonary drug delivery as an alternative to more expensive and less controllable formulation strategies.