Date of Award

Spring 2011

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemical Engineering - (Ph.D.)

Department

Chemical, Biological and Pharmaceutical Engineering

First Advisor

Boris Khusid

Second Advisor

Robert Benedict Barat

Third Advisor

Rajesh N. Dave

Fourth Advisor

Kamalesh K. Sirkar

Fifth Advisor

Paul Takhistov

Abstract

There is compelling evidence that variability in drug efficacy in individuals depends on their genetic fingerprints. These observations have given rise to the concept of personalized therapy whose ultimate goal is to develop medicinal agents designed for each niche of the population and individual patients according to their genetic background. The drawback in current pharmaceutical technologies is that most processes are designed to target large population and are unable to meet the demand of small-scale manufacturing of tailored therapeutics with diverse range of physical properties. One of the major challenges lie in developing efficient and cost effective methods of manufacturing personalized treatments.

Noncontact drop-on-demand (DOD) systems (i.e., drops are formed only as required) appear to be the most promising platform technology for small-scale manufacturing of personalized treatments. As a digital technology, DOD dosing is able to deposit precisely controlled amounts of material at exact locations without waste, rendering it especially attractive for use with expensive pharmaceutical products. It would provide the capability to form an individual dosage unit by printing a vast array of predefined amounts of therapeutics arranged in a specific pattern on a carrier substrate to achieve a desired drug release profile. However, current DOD methods developed for chemically and thermally stable, low-viscosity inks are of limited use for pharmaceuticals due to fundamentally different functional requirements.

In this dissertation, a recently developed DOD method for gentle printing of personalized medicines is presented. To eliminate adverse effects of electrochemical reactions at the fluid-electrode interface, the fluid was infused into an electrically insulating nozzle to form a pendant drop that served as a floating electrode capacitively coupled to external electrodes. A short voltage pulse was applied to the electrodes to stretch the drop into a liquid bridge that broke up creating a sessile drop on the substrate which could be post-processed into a final dosage form. Versatility was proved in experiments on fluids spanning over three orders of magnitude in viscosity and electric conductivity. This method can be used for printing fluids of different physical properties in pharmaceutical, biomedical, and biotechnology applications. Model for pendant drop and scaling analysis which captured the essential physics of electrodless electrohyrodynamic drop dynamics is presented. This analysis describes the characteristics of the operating regimes and provides critical design guideline.

To demonstrate the capability of electrodeless DOD for printing personalized dosages, assembled unit dosages were prepared by precisely loading porous hydroxy methylcellulose film matrix with controlled drops of model drugs dissolved in lowly volatile polyethylene glycol carrier. Dissolution tests were performed following United States Pharmacopeia (USP) protocol, and the drug release data was analyzed to identify the underlying drug release mechanisms from the assembled unit dosages. Data showed that the DOD method met the reproducibility requirement critical for content uniformity and that the porous film rapidly disintegrated resulting in instant release of drug which could be useful in fast orally dissolvable medicinal film dosage forms.

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