Abstract

The billion dollar pharmaceutical research and development pipeline suffers greatly from high attrition rates of novel therapeutic compounds within pre-clinical and clinical trials. Poor bioavailability in many new drugs, originating in the various methodologies of high throughput screening, may explain part of these growing failure rates. One interpretation of this phenomenon relies on bioavailability's correlation with aqueous solubility; much modern processing allows chemicals to fully develop without touching water, yielding upwards of 90% of new chemical entities practically insoluble in aqueous media. Thus, one approach to alleviating bioavailability and potentially clinical attrition rates necessitates augmented aqueous solubility. The amorphous nanoparticle presents the largest boost in aqueous solubility of a chemical through processing alone. In this contribution, we propose electrospray as a novel, competitive candidate to produce pharmaceutical amorphous nanoparticles with the intent of augmenting solubility. Electrospray represents an idyllic nominee for three reasons: repeatability, flexibility, and scalability. Electrospray offers low batch to batch variation with less than 30% relative standard deviation between various droplets. This triumphs over the several orders of magnitude in variation in pneumatic sprays. Electrospray's flexibility draws from its ability to attain diameters over several orders of magnitude, ranging from hundreds of microns to several nanometers; in this contribution droplets are produced between 500 nm and 1[micro]m. Finally, electrospray displays scalability to any industrial requirement; though a single nozzle operates at mere microliters per hour, a single multiplexed array of emitters may increase this throughput by several orders of magnitude. This exploration, utilizing Indomethacin as a model low solubility chemical, verifies electrospray as a compatible processing tool for the pharmaceutical industry. Scanning electron microscopy coupled with the image analysis software ImageJ gleans the size and shape of emitted (and dried) particles. Amorphicity verification of particles employs grazing angle x-ray diffraction. Finally, ultraviolet and visual spectrum spectroscopy evaluates the solubility advantage of particles.

Notes

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Thesis Completion

2014

Semester

Spring

Advisor

Deng, Wei Wei

Degree

Bachelor of Science in Mechanical Engineering (B.S.M.E.)

College

College of Engineering and Computer Science

Department

Mechanical and Aerospace Engineering

Degree Program

Mechanical Engineering

Subjects

Dissertations, Academic -- Engineering and Computer Science; Engineering and Computer Science -- Dissertations, Academic

Format

PDF

Identifier

CFH0004546

Language

English

Access Status

Open Access

Length of Campus-only Access

3 years

Document Type

Honors in the Major Thesis

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