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Date of Award

2009

Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmaceutical and Chemical Sciences

First Advisor

Bhaskara Jasti

Second Advisor

Xiaoling Li

First Committee Member

Silvio Rodriguez

Second Committee Member

Wade Russu

Third Committee Member

Jayne Hastedt

Abstract

Molecular interactions of small molecules with polymers in solid state have numerous applications in pharmaceutical research. This dissertation examines the mechanism of the solid state interactions of the biologically active sulfamide derivatives with polyethylene glycol (PEG) and structurally related polymers. It is shown that in addition to the formation of the eutectic systems, PEG and related polymers cause polymorphic transitions of sulfamide derivatives. A new polymorphic form of a model sulfamate, topiramate, has been discovered and characterized using multiple analytical techniques. The phase diagrams describing the interactions of Topiramate with PEG and poloxamer block copolymer in solid state were constructed and the mechanism of the polymorphic transformations has been proposed. It was concluded that formation and stabilization of the new polymorphs occurred due to rearrangement of the hydrogen bonding networks of the sulfamide derivatives caused by the conformational changes of the polymer chains.

Pages

156

ISBN

9781109250558

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