Date of Award

Fall 2015

Document Type

Thesis

Degree Name

Master of Science in Chemical Engineering - (M.S.)

Department

Chemical, Biological and Pharmaceutical Engineering

First Advisor

Ecevit Atalay Bilgili

Second Advisor

Costas G. Gogos

Third Advisor

S. Basuray

Fourth Advisor

Nicolas Ioannidis

Abstract

Drug nanoparticles can achieve targeting capabilities, enhanced dissolution rates and improved bioavailability when injected intravenously. Sterile filtration of drug nanoparticle suspensions (nanosuspensions) is critically needed for administration by intravenous delivery route. Avoiding gamma irradiation and high temperatures, sterile filtration could be an effective process to sterilize drug nanosuspensions. On the other hand, two major challenges must be tackled: drug particles must at least be smaller than the filter pore size and minimum amount of non-toxic stabilizers must be used to prevent side effects like pain on the injection site. The aim of this study is to prepare naproxen (NPX) nanosuspensions via wet stirred media milling using various polymers and surfactants as stabilizers and to assess their physical stability with the ultimate goal of achieving the sterile filterability of such produced suspensions. An intensified milling process was investigated for fast production of sub-200 nm drug particles. In the second part, various formulations to stabilize NPX nanoparticles were screened. Lastly, the suspensions with NPX particle size less than 220 nm were filtered through a sterile 0.22 μm disposable capsule filter. Laser diffraction, scanning electron microscopy, rheometry, and surface tension measurement were used to evaluate the breakage kinetics and storage stability. Although NPX nanosuspensions were stabilized using stabilizers acceptable for injection, their sterile filtration was not successful, indicating a critical need for further research regarding the use of acceptable stabilizers and filter type/processing.

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