THE SCHOOL OF MATERIALS SCIENCE AND ENGINEERING

GEORGIA INSTITUTE OF TECHNOLOGY

Under the provisions of the regulations for the degree

DOCTOR OF PHILOSOPHY

on Monday, December 3, 2018

10:00 AM
in MRDC 3515

will be held the

DISSERTATION PROPOSAL DEFENSE

for

Manali Banerjee

"Surface-modified cellulose nanocrystal gels for applications in pharmaceutical crystallization"

Committee Members:

Prof. Blair K. Brettmann, Advisor, MSE

Prof. Meisha L. Shofner, MSE

Prof. Robert J. Moon, RBI

Prof. Sven H. Behrens, CHBE

Abstract:

A significant research focus in the pharmaceutical industry is on methods to improve drug uptake into the body by increased dissolution of poorly water soluble active pharmaceutical ingredients (APIs) or sustained drug release behavior. Control over the solubility of the API is possible through heterogenous crystallization or crystallization in confined nanopores, which enables the directed nucleation of higher solubility API polymorphs. Gel phase crystallization allows the use of both these methods. Particles within the gel provide a surface for heterogeneous nucleation and the pores within the gel allow for confined homogenous nucleation.

This proposal outlines the development of natural material-based gels for API crystallization. Cellulose nanocrystals (CNCs) have a high surface area covered with readily-modifiable hydroxyl groups, which enable the production of CNCs with various surface functionalities. These surfaces can be used to form gels via network formation in organic solvents, which promotes API crystallization into desired polymorphs for higher solubility or controlled drug release behavior.

The first aim of this research is to develop CNC organogels and understand the gelation mechanism using selected functional groups to allow for control over the physical properties of the gels and the internal surface chemistries. The next aim is to address API crystallization within these gels and to use the highly tunable gel properties for directed crystallization of desired polymorphs.

The final aim presented in this proposal is to extend this work further through the development of aerogels. Aerogels provide a large surface area and controllable internal surface properties, which make them promising for crystallization of APIs. Therefore, this research will be extended to forming CNC aerogels with a variety of surface properties for directed API crystallization.

The overall aim of this research is to use CNC gels as supports for pharmaceutical crystallization, with an aim towards using the molecular interactions between nanocellulose and APIs to direct formation of desired polymorphs and crystal sizes, leading to flexibility for rational design of nanocellulose-drug composites.